PubMed

Related Articles Lipidomic Profiling Links the Fanconi Anemia Pathway to Glycosphingolipid Metabolism in Head and Neck Cancer Cells. Clin Cancer Res. 2018 06 01;24(11):2700-2709 Authors: Zhao X, Brusadelli MG, Sauter S, Butsch Kovacic M, Zhang W, Romick-Rosendale LE, Lambert PF, Setchell KDR, Wells SI Abstract Purpose: Mutations in Fanconi anemia (FA) genes are common in sporadic squamous cell carcinoma of the head and neck (HNSCC), and we have previously demonstrated that FA pathway depletion in HNSCC cell lines stimulates invasion. The goal of our studies was to use a systems approach in order to define FA pathway-dependent lipid metabolism and to extract lipid-based signatures and effectors of invasion in FA-deficient cells.Experimental Design: We subjected FA-isogenic HNSCC keratinocyte cell lines to untargeted and targeted lipidomics analyses to discover novel biomarkers and candidate therapeutic targets in FA-deficient cells. Cellular invasion assays were carried out in the presence and absence of N-butyldeoxynojirimycin (NB-DNJ), a biosynthetic inhibitor of the newly identified class of gangliosides, to investigate the requirement of ganglioside upregulation in FA-deficient HNSCC cells.Results: The most notable element of the lipid profiling results was a consistent elevation of glycosphingolipids, and particularly the accumulation of gangliosides. Conversely, repression of this same class of lipids was observed upon genetic correction of FA patient-derived HNSCC cells. Functional studies demonstrate that ganglioside upregulation is required for HNSCC cell invasion driven by FA pathway loss. The motility of nontransformed keratinocytes in response to FA loss displayed a similar dependence, thus supporting early and late roles for the FA pathway in controlling keratinocyte invasion through lipid regulation.Conclusions: Elevation of glycosphingolipids including the ganglioside GM3 in response to FA loss stimulates invasive characteristics of immortalized and transformed keratinocytes. An inhibitor of glycosphingolipid biosynthesis NB-DNJ attenuates invasive characteristics of FA-deficient HNSCC cells. Clin Cancer Res; 24(11); 2700-9. ©2018 AACR. PMID: 29530934 [PubMed - indexed for MEDLINE]

21 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 2019/12/20PubMed 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.

23 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 2019/12/19PubMed 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.

78 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 2019/12/18PubMed 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.

Macrophage inflammatory and metabolic responses to graphene-based nanomaterials differing in size and functionalization. Colloids Surf B Biointerfaces. 2019 Dec 05;186:110709 Authors: Cicuéndez M, Fernandes M, Ayán-Varela M, Oliveira H, Feito MJ, Diez-Orejas R, Paredes JI, Villar-Rodil S, Vila M, Portolés MT, Duarte IF Abstract The preparation of graphene-based nanomaterials (GBNs) with appropriate stability and biocompatibility is crucial for their use in biomedical applications. In this work, three GBNs differing in size and/or functionalization have been synthetized and characterized, and their in vitro biological effects were compared. Pegylated graphene oxide (GO-PEG, 200-500 nm) and flavin mononucleotide-stabilized pristine graphene with two different sizes (PG-FMN, 200-400 nm and 100-200 nm) were administered to macrophages, chosen as cellular model due to their key role in the processing of foreign materials and the regulation of inflammatory responses. The results showed that cellular uptake of GBNs was mainly influenced by their lateral size, while the inflammatory potential depended also on the type of functionalization. PG-FMN nanomaterials (both sizes) triggered significantly higher nitric oxide (NO) release, together with some intracellular metabolic changes, similar to those induced by the prototypical inflammatory stimulus LPS. NMR metabolomics revealed that macrophages incubated with smaller PG-FMN displayed increased levels of succinate, itaconate, phosphocholine and phosphocreatine, together with decreased creatine content. The latter two variations were also detected in cells incubated with larger PG-FMN nanosheets. On the other hand, GO-PEG induced a decrease in the inflammatory metabolite succinate and a few other changes distinct from those seen in LPS-stimulated macrophages. Assessment of TNF-α secretion and macrophage surface markers (CD80 and CD206) further corroborated the low inflammatory potential of GO-PEG. Overall, these findings revealed distinct phenotypic and metabolic responses of macrophages to different GBNs, which inform on their immunomodulatory activity and may contribute to guide their therapeutic applications. PMID: 31841776 [PubMed - as supplied by publisher]

Alterations in plasma concentrations of energy-balance-related metabolites in patients with lung, or head & neck, cancers: Effects of radiotherapy. J Proteomics. 2019 Dec 10;:103605 Authors: Rodríguez-Tomàs E, Arguís M, Arenas M, Fernández-Arroyo S, Murcia M, Sabater S, Torres L, Baiges-Gayà G, Hernández-Aguilera A, Camps J, Joven J Abstract We investigated the alterations in the plasma concentrations of energy-balance-related metabolites in patients with lung (LC) or head & neck (HNC) cancer and the changes on these parameters induced by radiotherapy. The study was conducted in 33 patients with non-small cell LC and 28 patients with HNC. We analyzed the concentrations of 17 metabolites involved in glycolysis, citric acid cycle and amino acid metabolism using targeted gas chromatography coupled to quadrupole time-of-flight mass spectrometry. For comparison, a control group of 50 healthy individuals was included in the present study. Patients with LC or HNC had significant alterations in the plasma levels of several energy-balance-related metabolites. Radiotherapy partially normalized these alterations in patients with LC, but not in those with HNC. The measurement of plasma glutamate concentration was an excellent predictor of the presence of LC or HNC, with sensitivity >90% and specificity >80%. Also, associations with disease prognosis were observed with plasma glutamate, amino acids and β-hydroxybutyrate concentrations. SIGNIFICANCE: This study analyzed the changes produced in the plasma concentrations of energy-balance-related metabolites in patients with lung cancer or head and neck cancer. The results obtained identified glutamate as the parameter with the highest discrimination capacity between patients and the control group. The relationships between various metabolites and clinical outcomes were also analyzed. These results extend the knowledge of metabolic alterations in cancer, thus facilitating the search for biomarkers and therapeutic targets. PMID: 31841666 [PubMed - as supplied by publisher]

Deep learning for the precise peak detection in high-resolution LC-MS data. Anal Chem. 2019 Dec 16;: Authors: Melnikov A, Tsentalovich YP, Yanshole VV Abstract This article is devoted to the application of machine learning, namely convolutional neural networks to solve problems in the initial steps of the common pipeline for data analysis in metabolomics. These steps are the peak detection and the peak integration in raw liquid chromatography - mass spectrometry (LC-MS) data. Widely used algorithms suffer from rather poor precision for these tasks, yielding many false positive signals. In the present work, we developed an algorithm named peakonly, which has high flexibility for the detection or exclusion of low-intensity noisy peaks, and shows excellent quality in the detection of true positive peaks, approaching the highest possible precision. The current approach was developed for the analysis of high-resolution LC-MS data for the purposes of metabolomics, but potentially it can be applied with several adaptations in other fields, which utilize high-resolution GC- or LC-MS techniques. Peakonly is freely available on GitHub (https://github.com/arseha/peakonly) under MIT license. PMID: 31841624 [PubMed - as supplied by publisher]

Effects of carbon sources on 17 beta-estradiol degradation by Sphingomonas sp. and the analysis of the involved intracellular metabolomics. Environ Sci Process Impacts. 2019 Dec 16;: Authors: Li C, Kong X, Lan L, Tadda MA, Liu D Abstract 17β-estradiol (E2) ubiquitously exists in various water bodies with long-term endocrine-disrupting and carcinogenic impacts on wildlife even at the trace level of ng L-1. However, it remains unclear how easy-to-degrade carbon sources alter E2 biodegradation patterns. In this study, E2 biodegradation by Sphingomonas sp. MCCC 1A06484 was investigated with regard to alternative carbon sources. Results showed that the bacterium preferentially utilized glucose, sodium succinate and sodium acetate over E2. Interestingly, the presence of these preferred nutrients increased the E2 removal efficiency by 20.1%. Furthermore, a positive relation (p < 0.05) between the utilization of total organic carbon (TOC) and E2 was found. Using intracellular metabolomics by UHPLC-QTOF-MS, 11 up-regulated and 35 down-regulated metabolites (variable importance > 1, p < 0.05) were identified in the bacterium when cultivated with E2 under various carbon and nitrogen backgrounds. The E2 exposure contributed to metabolism changes of lipid, nucleotide, carbohydrate, amino acid and membrane transport, which were considered to play roles in the E2 metabolism. The up-regulated phosphatidylcholine might act as an indicator during the bacterial degradation of E2. Generally, this study contributes to an in-depth understanding of E2 biodegradation in complex environments with multiple carbon and nitrogen sources. PMID: 31841122 [PubMed - as supplied by publisher]

Re: Metabolomics Analysis of Blood Identifies Potential Biomarkers and Possible Treatment Targets for Nocturia. J Urol. 2019 Dec 16;:101097JU000000000000066202 Authors: Kaplan SA PMID: 31841074 [PubMed - as supplied by publisher]

'Omics': The new language in medicine that we all must learn. Respirology. 2019 Dec 16;: Authors: Moodley Y, Yang IA PMID: 31840902 [PubMed - as supplied by publisher]

Metabolic changes in mice cardiac tissue after low-dose irradiation revealed by 1H NMR spectroscopy. J Radiat Res. 2019 Dec 16;: Authors: Gramatyka M, Boguszewicz ᴌ, Ciszek M, Gabryś D, Kulik R, Sokół M Abstract Ionizing radiation may cause cardiotoxicity not only at high, but even at low (considered as harmless) doses, yet the molecular mechanisms of the heart's response to low doses are not clear. In this work, we used high-resolution nuclear magnetic resonance (NMR) spectroscopy to detect the early and late effects of radiation on the metabolism of murine hearts. The hearts of C57Bl/6NCrl female mice were irradiated in vivo with single 0.2 Gy or 2 Gy doses using 6 MV photons, then tissues were collected 48 h and 20 weeks after exposure. The most distinct changes in the profile of polar metabolites were detected 48 h after irradiation with 2 Gy, and included increased levels of pantothenate and glutamate as well as decreased levels of alanine, malonate, acetylcarnitine, glycine and adenosine. Significant effects of the 2 Gy dose were also observed 20 weeks after irradiation and included decreased levels of glutamine and acetylcarnitine when compared with age-matched controls. Moreover, several differences were observed between hearts irradiated with 2 Gy and analyzed either 48 h or 20 weeks after the exposure, which included changes in levels of acetylcarnitine, alanine, glycine, glutamate, glutamine, formate, myo-inositol and trimethylamine. No statistically significant effects induced by the 0.2 Gy dose were observed 20 weeks after irradiation. In general, radiation-affected compounds were associated with energy metabolism, fatty acid beta-oxidation, oxidative stress and damage to cell structures. At the same time, radiation-related effects were not detected at the level of tissue histology, which indicated a higher sensitivity of metabolomics-based tests for cardiac tissue response to radiation. PMID: 31840756 [PubMed - as supplied by publisher]

Related Articles Metabolic compounds within the porcine uterine environment are unique to the type of conceptus present during the early stages of blastocyst elongation. Mol Reprod Dev. 2019 Dec 16;: Authors: Walsh SC, Miles JR, Yao L, Broeckling CD, Rempel LA, Wright-Johnson EC, Pannier AK Abstract The objective of this study was to identify metabolites within the porcine uterine milieu during the early stages of blastocyst elongation. At Days 9, 10, or 11 of gestation, reproductive tracts of White cross-bred gilts (n = 38) were collected immediately following harvest and flushed with Roswell Park Memorial Institute-1640 medium. Conceptus morphologies were assessed from each pregnancy and corresponding uterine flushings were assigned to one of five treatment groups based on these morphologies: (a) uniform spherical (n = 8); (b) heterogeneous spherical and ovoid (n = 8); (c) uniform ovoid (n = 8); (d) heterogeneous ovoid and tubular (n = 8); and (e) uniform tubular (n = 6). Uterine flushings from these pregnancies were submitted for nontargeted profiling by gas chromatography-mass spectrometry (GC-MS) and ultra performance liquid chromatography (UPLC)-MS techniques. Unsupervised multivariate principal component analysis (PCA) was performed using pcaMethods and univariate analysis of variance was performed in R with false discovery rate (FDR) adjustment. PCA analysis of the GC-MS and UPLC-MS data identified 153 and 104 metabolites, respectively. After FDR adjustment of the GC-MS and UPLC-MS data, 38 and 59 metabolites, respectively, differed (p < .05) in uterine flushings from pregnancies across the five conceptus stages. Some metabolites were greater (p  < .05) in abundance for uterine flushings containing earlier stage conceptuses (i.e., spherical), such as uric acid, tryptophan, and tyrosine. In contrast, some metabolites were greater (p < .05) in abundance for uterine flushings containing later stage conceptuses (i.e., tubular), such as creatinine, serine, and urea. These data illustrate several putative metabolites that change within the uterine milieu during early porcine blastocyst elongation. PMID: 31840336 [PubMed - as supplied by publisher]

Related Articles Matrix-assisted laser desorption/ionization mass spectrometry imaging to uncover protein alterations associated with the progression of IgA nephropathy. Virchows Arch. 2019 Dec 14;: Authors: Ivanova M, Dyadyk O, Ivanov D, Clerici F, Smith A, Magni F Abstract IgA nephropathy (IgAN) is one of the most diffuse glomerulonephrites worldwide, and many issues still remain regarding our understanding of its pathogenesis. The disease is diagnosed by renal biopsy examination, but potential pitfalls still persist with regard to discriminating its primary origin and, as a result, determining patient outcome remains challenging. In this pilot study, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) was performed on renal biopsies obtained from patients with IgAN (n = 11) and other mesangioproliferative glomerulonephrites (MesPGN, n = 6) in order to enlighten proteomic alterations that may be associated with the progression of IgAN. Differences in the proteomic profiles of IgAN and MesPGN tissue could clearly be detected using this approach and, furthermore, 14 signals (AUC ≥ 0.8) were observed to have an altered intensity among the different CKD stages within the IgAN group. In particular, large increases in the intensity of these signals could be observed at CKD stages II and above. These signals primarily corresponded to proteins involved in either inflammatory and healing pathways and their increased intensity was localized within regions of tissue with large amounts of inflammatory cells or sclerosis. Despite much work in recent years, our molecular understanding of IgAN progression remains incomplete. This pilot study represents a promising starting point in the search for novel protein markers that can assist clinicians in better understanding the pathogenesis of IgAN and highlighting those patients who may progress to end-stage renal disease. PMID: 31838587 [PubMed - as supplied by publisher]

Implications of gut microbiota dysbiosis and metabolic changes in prion disease. Neurobiol Dis. 2019 Dec 11;:104704 Authors: Yang D, Zhao D, Shah SZA, Wu W, Lai M, Zhang X, Li J, Guan Z, Zhao H, Li W, Gao H, Zhou X, Yang L Abstract Evidence of the gut microbiota influencing neurodegenerative diseases has been reported for several neural diseases. However, there is little insight regarding the relationship between the gut microbiota and prion disease. Here, using fecal samples of 12 prion-infected mice and 25 healthy controls, we analyzed the structure of the gut microbiota and metabolic changes by 16S rRNA sequencing and LC-MS-based metabolomics respectively as multi-omic analyses. Additionally, SCFAs and common amino acids were detected by GC-MS and UPLC respectively. Enteric changes induced by prion disease affected both structure and abundances of the gut microbiota. The gut microbiota of infected mice displayed greater numbers of Proteobacteria and less Saccharibacteria at the phylum level and more Lactobacillaceae and Helicobacteraceae and less Prevotellaceae and Ruminococcaceae at the family level. A total of 145 fecal metabolites were found to be significantly different in prion infection, and most (114) of these were lipid metabolites. Using KEGG pathway enrichment analysis, we found that 3 phosphatidylcholine (PC) compounds significantly decreased and 4 hydrophobic bile acids significantly increased. Decreases of 8 types of short-chain acids (SCFAs) and increases of Cys and Tyr and decreases of His, Trp, and Arg were observed in prion infection. Correlation analysis indicated that the gut microbiota changes observed in our study may have been the shared outcome of prion disease. These findings suggest that prion disease can cause significant shifts in the gut microbiota. Certain bacterial taxa can then respond to the resulting change to the enteric environment by causing dramatic shifts in metabolite levels. Our data highlight the health impact of the gut microbiota and related metabolites in prion disease. PMID: 31837420 [PubMed - as supplied by publisher]

Related Articles Gut microbiome and cardiometabolic risk. Rev Endocr Metab Disord. 2019 Dec 14;: Authors: Kappel BA, Federici M Abstract The last decade has been characterized by an intense research on the composition of the gut microbiome and the links with human health. While previous work was focused on the effects of prebiotics and probiotics, nowadays several laboratories are describing the gut microbiome and its metabolic functions. Gut microbiome interaction with nutrients allows the gut microbiome to survive and at the same time determines the production of metabolites that are either adsorbed by intestinal cell in a mutual relationship or promote detrimental effect. Metabolomics, a new method to approach identification of biomarkers has been used to identify small metabolites in blood and other biofluids. The study of metabolome revealed several microbial derived metabolites that are circulating in blood and potentially affect human health. In this review we describe the links between regulation of metabolism and microbial derived metabolites. PMID: 31836950 [PubMed - as supplied by publisher]

Related Articles Metabolomic Profiles of Bovine Mammary Epithelial Cells Stimulated by Lipopolysaccharide. Sci Rep. 2019 Dec 13;9(1):19131 Authors: Huang Y, Shen L, Jiang J, Xu Q, Luo Z, Luo Q, Yu S, Yao X, Ren Z, Hu Y, Yang Y, Cao S Abstract Bovine mammary epithelial cells (bMECs) are the main cells of the dairy cow mammary gland. In addition to their role in milk production, they are effector cells of mammary immunity. However, there is little information about changes in metabolites of bMECs when stimulated by lipopolysaccharide (LPS). This study describes a metabolomics analysis of the LPS-stimulated bMECs to provide a basis for the identification of potential diagnostic screening biomarkers and possible treatments for bovine mammary gland inflammation. In the present study, bMECs were challenged with 500 ng/mL LPS and samples were taken at 0 h, 12 h and 24 h post stimulation. Metabolic changes were investigated using high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF MS) with univariate and multivariate statistical analyses. Clustering and metabolic pathway changes were established by MetaboAnalyst. Sixty-three differential metabolites were identified, including glycerophosphocholine, glycerol-3-phosphate, L-carnitine, L-aspartate, glutathione, prostaglandin G2, α-linolenic acid and linoleic acid. They were mainly involved in eight pathways, including D-glutamine and D-glutamic acid metabolism; linoleic acid metabolism; α-linolenic metabolism; and phospholipid metabolism. The results suggest that bMECs are able to regulate pro-inflammatory, anti-inflammatory, antioxidation and energy-producing related metabolites through lipid, antioxidation and energy metabolism in response to inflammatory stimuli. PMID: 31836784 [PubMed - in process]

Related Articles Metabolomics analysis of human acute graft-versus-host disease reveals changes in host and microbiota-derived metabolites. Nat Commun. 2019 Dec 13;10(1):5695 Authors: Michonneau D, Latis E, Curis E, Dubouchet L, Ramamoorthy S, Ingram B, de Latour RP, Robin M, de Fontbrune FS, Chevret S, Rogge L, Socié G Abstract Despite improvement in clinical management, allogeneic hematopoietic stem cell transplantation (HSCT) is still hampered by high morbidity and mortality rates, mainly due to graft versus host disease (GvHD). Recently, it has been demonstrated that the allogeneic immune response might be influenced by external factors such as tissues microenvironment or host microbiota. Here we used high throughput metabolomics to analyze two cohorts of genotypically HLA-identical related recipient and donor pairs. Metabolomic profiles markedly differ between recipients and donors. At the onset of acute GvHD, in addition to host-derived metabolites, we identify significant variation in microbiota-derived metabolites, especially in aryl hydrocarbon receptor (AhR) ligands, bile acids and plasmalogens. Altogether, our findings support that the allogeneic immune response during acute GvHD might be influenced by bile acids and by the decreased production of AhR ligands by microbiota that could limit indoleamine 2,3-dioxygenase induction and influence allogeneic T cell reactivity. PMID: 31836702 [PubMed - in process]

Related Articles Multi-omic characterisation of the mode of action of a potent new antimalarial compound, JPC-3210, against Plasmodium falciparum. Mol Cell Proteomics. 2019 Dec 13;: Authors: Birrell GW, Challis MP, De Paoli A, Anderson D, Devine SM, Heffernan GD, Jacobus DP, Edstein MD, Siddiqui G, Creek DJ Abstract The increasing incidence of antimalarial drug resistance to the first-line artemisinin combination therapies underpins an urgent need for new antimalarial drugs, ideally with a novel mode of action. The recently developed 2-aminomethylphenol, JPC-3210, (MMV 892646) is an erythrocytic schizonticide with potent in vitro antimalarial activity against multidrug-resistant Plasmodium falciparum lines, low cytotoxicity, potent in vivo efficacy against murine malaria, and favourable preclinical pharmacokinetics including a lengthy plasma elimination half-life. To investigate the impact of JPC-3210 on biochemical pathways within P. falciparum-infected red blood cells, we have applied a "multi-omics" workflow based on high resolution orbitrap mass spectrometry combined with biochemical approaches. Metabolomics, peptidomics and hemoglobin fractionation analyses revealed a perturbation in hemoglobin metabolism following JPC-3210 exposure. The metabolomics data demonstrated a specific depletion of short hemoglobin-derived peptides, peptidomics analysis revealed a depletion of longer hemoglobin-derived peptides, and the hemoglobin fractionation assay demonstrated decreases in hemoglobin, heme and hemozoin levels. In order to further elucidate the mechanism responsible for inhibition of hemoglobin metabolism, we used in vitro β-hematin polymerisation assays and showed JPC-3210 to be an intermediate inhibitor of β-hematin polymerisation, about 10-fold less potent then the quinoline antimalarials, such as chloroquine and mefloquine. Furthermore, quantitative proteomics analysis showed that JPC-3210 treatment results in a distinct proteomic signature in comparison to other known antimalarials. Whilst JPC-3210 clustered closely with mefloquine in the metabolomics and proteomics analyses, a key differentiating signature for JPC-3210 was the significant enrichment of parasite proteins involved in regulation of translation. These studies revealed that the mode of action for JPC-3210 involves inhibition of the hemoglobin digestion pathway and elevation of regulators of protein translation. Importantly, JPC-3210 demonstrated rapid parasite killing kinetics compared to other quinolones, suggesting that JPC-3210 warrants further investigation as a potentially long acting partner drug for malaria treatment. PMID: 31836637 [PubMed - as supplied by publisher]

Related Articles Reactive oxygen species detection-approaches in plants: insights into genetically encoded FRET-based sensors. J Biotechnol. 2019 Dec 10;: Authors: Anjum NA, Amreen, Tantray AY, Khan NA, Ahmad A Abstract The generation of reactive oxygen species (ROS) (and their reaction products) in abiotic stressed plants can be simultaneous. Hence, it is very difficult to establish individual roles of ROS (and their reaction products) in plants particularly under abiotic stress conditions. It is highly imperative to detect ROS (and their reaction products) and ascertain their role in vivo and also to point their optimal level in order to unveil exact relation of ROS (and their reaction products) with the major components of ROS-controlling systems. Förster Resonance Energy Transfer (FRET) technology enables us with high potential for monitoring and quantification of ROS and redox variations, avoiding some of the obstacles presented by small-molecule fluorescent dyes. This paper aims to: (i) introduce ROS and overview ROS-chemistry and ROS-accrued major damages to major biomolecules; (ii) highlight invasive and non-invasive approaches for the detection of ROS (and their reaction products); (iii) appraise literature available on genetically encoded ROS (and their reaction products)-sensors based on FRET technology, and (iv) enlighten so far unexplored aspects in the current context. The studies integrating the outcomes of the FRET-based ROS-detection approaches with the OMICS (genetics, genomics, proteomics, and metabolomics) would enlighten insights into real-time ROS and redox dynamics, and their signaling at cellular and subcellular levels in living cells. PMID: 31836526 [PubMed - as supplied by publisher]

Related Articles Antileishmanial Compounds Isolated from Psidium Guajava L. Using a Metabolomic Approach. Molecules. 2019 Dec 11;24(24): Authors: Phakeovilay C, Bourgeade-Delmas S, Perio P, Valentin A, Chassagne F, Deharo E, Reybier K, Marti G Abstract With an estimated annual incidence of one million cases, leishmaniasis is one of the top five vector-borne diseases. Currently available medical treatments involve side effects, including toxicity, non-specific targeting, and resistance development. Thus, new antileishmanial chemical entities are of the utmost interest to fight against this disease. The aim of this study was to obtain potential antileishmanial natural products from Psidium guajava leaves using a metabolomic workflow. Several crude extracts from P. guajava leaves harvested from different locations in the Lao People's Democratic Republic (Lao PDR) were profiled by liquid chromatography coupled to high-resolution mass spectrometry, and subsequently evaluated for their antileishmanial activities. The putative active compounds were highlighted by multivariate correlation analysis between the antileishmanial response and chromatographic profiles of P. guajava mixtures. The results showed that the pooled apolar fractions from P. guajava were the most active (IC50 = 1.96 ± 0.47 µg/mL). Multivariate data analysis of the apolar fractions highlighted a family of triterpenoid compounds, including jacoumaric acid (IC50 = 1.318 ± 0.59 µg/mL) and corosolic acid (IC50 = 1.01 ± 0.06 µg/mL). Our approach allowed the identification of antileishmanial compounds from the crude extracts in only a small number of steps and can be easily adapted for use in the discovery workflows of several other natural products. PMID: 31835791 [PubMed - in process]