PubMed

Related Articles Determinants of accelerated metabolomic and epigenetic aging in a UK cohort. Aging Cell. 2020 May 03;: Authors: Robinson O, Chadeau Hyam M, Karaman I, Climaco Pinto R, Ala-Korpela M, Handakas E, Fiorito G, Gao H, Heard A, Jarvelin MR, Lewis M, Pazoki R, Polidoro S, Tzoulaki I, Wielscher M, Elliott P, Vineis P Abstract Markers of biological aging have potential utility in primary care and public health. We developed a model of age based on untargeted metabolic profiling across multiple platforms, including nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry in urine and serum, within a large sample (N = 2,239) from the UK Airwave cohort. We validated a subset of model predictors in a Finnish cohort including repeat measurements from 2,144 individuals. We investigated the determinants of accelerated aging, including lifestyle and psychological risk factors for premature mortality. The metabolomic age model was well correlated with chronological age (mean r = .86 across independent test sets). Increased metabolomic age acceleration (mAA) was associated after false discovery rate (FDR) correction with overweight/obesity, diabetes, heavy alcohol use and depression. DNA methylation age acceleration measures were uncorrelated with mAA. Increased DNA methylation phenotypic age acceleration (N = 1,110) was associated after FDR correction with heavy alcohol use, hypertension and low income. In conclusion, metabolomics is a promising approach for the assessment of biological age and appears complementary to established epigenetic clocks. PMID: 32363781 [PubMed - as supplied by publisher]

Related Articles Group testing in mediation analysis. Stat Med. 2020 May 04;: Authors: Derkach A, Moore SC, Boca SM, Sampson JN Abstract We consider the scenario where there is an exposure, multiple biologically defined sets of biomarkers, and an outcome. We propose a new two-step procedure that tests if any of the sets of biomarkers mediate the exposure/outcome relationship, while maintaining a prespecified familywise error rate. The first step of the proposed procedure is a screening step that removes all groups that are unlikely to be strongly associated with both the exposure and the outcome. The second step adapts recent advances in postselection inference to test if there are true mediators in each of the remaining candidate sets. We use simulation to show that this simple two-step procedure has higher statistical power to detect true mediating sets when compared with existing procedures. We then use our two-step procedure to identify a set of Lysine-related metabolites that potentially mediate the known relationship between increased body mass index and the increased risk of estrogen-receptor positive breast cancer in postmenopausal women. PMID: 32363646 [PubMed - as supplied by publisher]

Related Articles Fecal Microbial and Metabolic Profiles in Dogs With Acute Diarrhea Receiving Either Fecal Microbiota Transplantation or Oral Metronidazole. Front Vet Sci. 2020;7:192 Authors: Chaitman J, Ziese AL, Pilla R, Minamoto Y, Blake AB, Guard BC, Isaiah A, Lidbury JA, Steiner JM, Unterer S, Suchodolski JS Abstract The aim was to characterize differences in fecal consistency, and fecal microbiota and metabolome profiles in dogs with acute diarrhea (AD) treated with either fecal microbiota transplantation as enema (FMT; n = 11) or oral metronidazole (MET; n = 7) for 7 days. On days 0, 7, and 28 fecal samples were obtained. Fecal samples from healthy dogs (HC; n = 14) were used for comparison. Samples were analyzed by the previously validated qPCR based canine Dysbiosis Index (DI; increased values indicate microbiota dysbiosis) and 16S rRNA gene sequencing. The fecal metabolome was analyzed using a previously validated targeted canine assay for fecal unconjugated bile acids, and untargeted metabolomics. Fecal consistency improved significantly in dogs treated with FMT and MET by day 7 and day 28 (p < 0.01) compared to day 0. However, on day 28 fecal consistency was significantly better in FMT compared to MET (p = 0.040). At day 0, dogs with AD had an altered microbiota indicated by significantly increased DI, decreased alpha-diversity, and altered beta-diversity. In the FMT group, the DI decreased over time, while MET led to a significant increase in the dysbiosis index at day 7 and 28 compared to FMT. Sequencing data revealed that in FMT microbial diversity and beta-diversity was similar to HC at day 28, while in MET these parameters were still significantly different from HC. In dogs treated with FMT, a decrease in cholic acid and the percentage of primary bile acids was observed, whereas treatment with metronidazole led to an increase in cholic acid at day 7 and an increase in percentage of primary bile acids over time. Based on untargeted metabolomics, dogs with AD had an altered fecal metabolome compared to HC. Dogs treated with FMT clustered closer to HC at day 28, while dogs treated with MET did not. In this pilot study, dogs with AD had significant differences in fecal microbiota and metabolome profiles. Dogs treated with MET still had altered microbial and metabolic profiles at day 28 compared to dogs treated with FMT or healthy dogs. PMID: 32363202 [PubMed]

Related Articles Omics-Based Mechanistic Insight Into the Role of Bioengineered Nanoparticles for Biotic Stress Amelioration by Modulating Plant Metabolic Pathways. Front Bioeng Biotechnol. 2020;8:242 Authors: Kumari M, Pandey S, Mishra SK, Giri VP, Agarwal L, Dwivedi S, Pandey AK, Nautiyal CS, Mishra A Abstract Bioengineered silver nanoparticles can emerge as a facile approach to combat plant pathogen, reducing the use of pesticides in an eco-friendly manner. The plants' response during tripartite interaction of plant, pathogen, and nanoparticles remains largely unknown. This study demonstrated the use of bioengineered silver nanoparticles in combating black spot disease caused by necrotrophic fungus Alternaria brassicicola in Arabidopsis thaliana via foliar spray. The particles reduced disease severity by 70-80% at 5 μg/ml without showing phytotoxicity. It elicited plant immunity by a significant reduction in reactive oxygen species (ROS), decreases in stress enzymes by 0.6-19.8-fold, and emergence of autophagy. Comparative plant proteomics revealed 599 proteins expressed during the interaction, where 117 differential proteins were identified. Among different categories, proteins involved in bioenergy and metabolism were most abundant (44%), followed by proteins involved in plant defense (20%). Metabolic profiling by gas chromatography-mass spectroscopy yielded 39 metabolite derivatives in non-polar fraction and 25 in the polar fraction of plant extracts. It was observed that proteins involved in protein biogenesis and early plant defense were overexpressed to produce abundant antimicrobial metabolites and minimize ROS production. Bioengineered silver nanoparticles performed dual functions to combat pathogen attack by killing plant pathogen and eliciting immunity by altering plant defense proteome and metabolome. PMID: 32363178 [PubMed]

Related Articles FLT3LG - a biomarker reflecting clinical responses to the immunogenic cell death inducer oxaliplatin. Oncoimmunology. 2020;9(1):1755214 Authors: Pol JG, Le Naour J, Kroemer G Abstract The fms-related tyrosine kinase 3 (FLT3) ligand (FLT3LG) binds to FLT3 on dendritic cells to stimulate their differentiation and expansion, hence facilitating tumor antigen cross-presentation and anticancer immune responses. A recent study by Abrahamsson et al. demonstrates that, in patients receiving a hepatic arterial infusion of oxaliplatin for the treatment of colorectal cancer metastases, an increase in circulating FLT3LG predicts long-term survival of those individuals whose metastases have been rendered resectable. Thus, FLT3LG constitutes a potential biomarker of immune activation by immunogenic cell death-inducing chemotherapeutics such as oxaliplatin. Abbreviations: DC, dendritic cell; FLT3, fms-related tyrosine kinase 3; FLT3LG, FLT3 ligand; ICI, immune checkpoint inhibitor; OXA, oxaliplatin. PMID: 32363127 [PubMed]

Related Articles Omics and the molecular exercise physiology. Adv Clin Chem. 2020;96:55-84 Authors: Gomes C, Almeida JA, Franco OL, Petriz B Abstract Exercise is a well-known non-pharmacologic agent used to prevent and treat a wide range of pathologic conditions such as metabolic and cardiovascular disease. In this sense, the classic field of exercise physiology has determined the main theoretical and practical bases of physiologic adaptations in response to exercise. However, the last decades were marked by significant advances in analytical laboratory techniques, where the field of biochemistry, genetics and molecular biology promoted exercise science to enter a new era. Regardless of its application, whether in the field of disease prevention or performance, the association of molecular biology with exercise physiology has been fundamental for unveiling knowledge of the molecular mechanisms related to the adaptation to exercise. This chapter will address the natural evolution of exercise physiology toward genetics and molecular biology, emphasizing the collection of integrated analytical approaches that composes the OMICS and their contribution to the field of molecular exercise physiology. PMID: 32362320 [PubMed - in process]

Related Articles New biomarkers in non-Hodgkin lymphoma and acute leukemias. Adv Clin Chem. 2020;96:19-53 Authors: Rubio-Jurado B, Sosa-Quintero LS, Carrasco-Martinez IL, Norato-Delgado A, Garcia-Luna E, Guzmán-Silahua S, Riebeling-Navarro C, Nava-Zavala AH Abstract Biomarkers play a critical role in the medical care of patients with cancer, including in early detection of the disease, diagnostic accuracy, risk stratification, treatment, and follow-up. Biomarkers in hematological malignancies can support the redefinition of the diagnosis and adjustments in the treatment plan. Biomarkers can be classified into 4 categories: (1) protein antigens, (2) cytogenetic abnormalities, (3) genetic polymorphisms, and (4) gene expression. Efforts in genomics, proteomics, and metabolomics to observe new biomarkers that contribute to the development of clinical medicine with greater precision in the strategies that improve prevention, diagnosis, and treatment of patients with malignant hematological disease. New biomarkers should accomplish several issues such as the biological plausibility, methodology used, analytical validation, intellectual property registry, and legal framework of application. This knowledge should be transferred to health professionals who can carry out the process of its implementation in clinical practice. PMID: 32362319 [PubMed - in process]

Related Articles Microplastics enhance the developmental toxicity of synthetic phenolic antioxidants by disturbing the thyroid function and metabolism in developing zebrafish. Environ Int. 2020 Apr 29;140:105750 Authors: Zhao HJ, Xu JK, Yan ZH, Ren HQ, Zhang Y Abstract Coexposure of MPs and other contaminants adsorbed from the environment has raised many attentions, but the understanding of the combined effects of MPs and plastic additives are limited. Butylated hydroxyanisole (BHA), a widely used synthetic phenolic antioxidant in plastics, has gained high concerns due to their unintended environmental release and potential threat to aquatic organisms. This study was conducted to reveal the influences of MPs on the bioaccumulation and developmental toxicity of BHA in zebrafish larvae. As a result, MPs promoted the accumulation of BHA in zebrafish larvae and enhanced the toxicity of BHA in larvae development manifested by reduced hatching rates, increased malformation rates and decreased calcified vertebrae. Although the concentration of MPs was not sufficient to cause obvious developmental toxicity, the impacts of MPs on thyroid hormones status might contribute to the aggravated join toxicity. The metabolomic mechanism was revealed to be that the coexposure of BHA and MPs affected the development of zebrafish larvae via disturbing the metabolism of arachidonic acid, glycerophospholipid, and lipids. Our results emphasized that MPs, even at the nontoxic concentrations, in combination with additives caused health risk that should not be ignored. PMID: 32361124 [PubMed - as supplied by publisher]

Related Articles Correlations between soil metabolomics and bacterial community structures in the pepper rhizosphere under plastic greenhouse cultivation. Sci Total Environ. 2020 Apr 23;728:138439 Authors: Song Y, Li X, Yao S, Yang X, Jiang X Abstract Microbial communities in the plant rhizosphere are critical drivers of soil organic matter conversion and thus affect plant growth, especially under plastic greenhouse vegetable cultivation (PGVC). By high-throughput sequencing and soil metabolomics, we investigated the differential structures and functions of the soil bacterial community in pepper rhizosphere and bulk soils under PGVC. It was found that the soil properties, including the total dissolved organic carbon content, did not show significant differences between the rhizosphere and bulk soil. However, the soil metabolite profiles and the soil bacterial community structures changed in pepper rhizosphere. Eleven differential metabolites were detected between rhizosphere and bulk soils, including organic acids and sugars, which were positively or negatively correlated with the relative abundances of the differential bacteria. Pathway enrichment analysis indicated that the most differentially expressed metabolic pathway was starch and sucrose metabolism, and the main functional genes participating in this pathway were predicted to be downregulated in rhizosphere soil. This study linked the differential soil microbe and soil metabolite profiles in the pepper rhizosphere under PGVC and provided new insights into plant-microbe interactions in soil. PMID: 32361108 [PubMed - as supplied by publisher]

Related Articles Flavokawain A inhibits prostate cancer cells by inducing cell cycle arrest and cell apoptosis and regulating the glutamine metabolism pathway. J Pharm Biomed Anal. 2020 Apr 04;186:113288 Authors: Wang K, Zhang W, Wang Z, Gao M, Wang X, Han W, Zhang N, Xu X Abstract Flavokawain A (FKA), a major chalcone in kava extracts, has exhibited anti-proliferative and apoptotic effects in the prostate cancer. However, the molecular mechanism of FKA remains unclear. In this study, FKA induces cell apoptosis and cell cycle arrest in a G2M phase to prostate cancer cells. FKA interferes with tubulin polymerization and inhibits survivin expression in PC3 cells. Molecular docking simulation experiment finds that FKA can bind to colchicine binding sites that inhibit tubulin polymerization. FKA treatment regulates the glutamine metabolism pathway in PC3 cells by reducing intracellular glutamine, glutamic and proline. FKA treatment also decreases the GSH content by decreasing the activity of GSH synthetase (GSS) and increasing the activity of glutathione thiol transferase (GSTP1), which subsequently induces ROS production and PC3 cell apoptosis. PMID: 32361091 [PubMed - as supplied by publisher]

Related Articles Suspect and non-targeted screening of chemicals of emerging concern for human biomonitoring, environmental health studies and support to risk assessment: From promises to challenges and harmonisation issues. Environ Int. 2020 Apr 28;139:105545 Authors: Pourchet M, Debrauwer L, Klanova J, Price EJ, Covaci A, Caballero-Casero N, Oberacher H, Lamoree M, Damont A, Fenaille F, Vlaanderen J, Meijer J, Krauss M, Sarigiannis D, Barouki R, Le Bizec B, Antignac JP Abstract Large-scale suspect and non-targeted screening approaches based on high-resolution mass spectrometry (HRMS) are today available for chemical profiling and holistic characterisation of biological samples. These advanced techniques allow the simultaneous detection of a large number of chemical features, including markers of human chemical exposure. Such markers are of interest for biomonitoring, environmental health studies and support to risk assessment. Furthermore, these screening approaches have the promising capability to detect chemicals of emerging concern (CECs), document the extent of human chemical exposure, generate new research hypotheses and provide early warning support to policy. Whilst of growing importance in the environment and food safety areas, respectively, CECs remain poorly addressed in the field of human biomonitoring. This shortfall is due to several scientific and methodological reasons, including a global lack of harmonisation. In this context, the main aim of this paper is to present an overview of the basic principles, promises and challenges of suspect and non-targeted screening approaches applied to human samples as this specific field introduce major specificities compared to other fields. Focused on liquid chromatography coupled to HRMS-based data acquisition methods, this overview addresses all steps of these new analytical workflows. Beyond this general picture, the main activities carried out on this topic within the particular framework of the European Human Biomonitoring initiative (project HBM4EU, 2017-2021) are described, with an emphasis on harmonisation measures. PMID: 32361063 [PubMed - as supplied by publisher]

Related Articles 22β-hydroxytingenone reduces proliferation and invasion of human melanoma cells. Toxicol In Vitro. 2020 Apr 29;:104879 Authors: Aranha ESP, da Silva EL, Mesquita FP, de Sousa LB, da Silva FMA, Rocha WC, Lima ES, Koolen HHF, de Moraes MEA, Montenegro RC, de Vasconcellos MC Abstract Melanoma is a skin cancer with high invasive potential and high lethality. Considering that quinonemethide triterpenes are described as promising anticancer agents, the aim of this study was to evaluate the effect of 22β-hydroxytingenone (22-HTG) against human melanoma cells. Alamar blue assay was performed in order to evaluate its cytotoxic effect. Thus, subtoxic concentrations (1.0, 2.0, and 2.5 μM) were used to evaluate the effect of this compound on proliferation, migration, metabolism, and invasion. IC50 value against SK-MEL-28 cell line was 4.35, 3.72, and 3.29 μM after 24, 48, and 72 h of incubation, respectively. 22-HTG reduced proliferation, migration and invasion by melanoma cells, with decreased activity of metalloproteinases (MMP-2 and MMP-9). Futhermore, 22-HTG decreased expression of lactate dehydrogenase (LDHA), an enzyme associated with cell metabolism. Howerver, the small reduction in LDHA enzyme activity must have occurred by the cytotoxic effect of 22-HTG. According to the results, 22-HTG interferes with important characteristics of cancer, with anti-proliferative, and anti-invasive effect against melanoma cells. The data suggest that 22-HTG is an effective substance against melanoma cells and it should be considered as a potential anticancer agent. PMID: 32360863 [PubMed - as supplied by publisher]

Related Articles Plasma metabolite biomarkers predictive of radiation induced cardiotoxicity. Radiother Oncol. 2020 Apr 20;: Authors: Unger K, Li Y, Yeh C, Barac A, Srichai MB, Ballew EA, Girgis M, Jayatilake M, Sridharan V, Boerma M, Cheema AK Abstract PURPOSE: Although advancements in cancer treatments using radiation therapy (RT) have led to improved outcomes, radiation-induced heart disease (RIHD) remains a significant source of morbidity and mortality in survivors of cancers in the chest. Currently, there are no diagnostic tests in clinical use due to a lack of understanding of the natural history and mechanisms of RIHD development. Few studies have examined the utility of using metabolomics to prospectively identify cancer survivors who are at risk of developing cardiotoxicity. METHODS: We analyzed plasma and left ventricle heart tissue samples collected from a cohort of male Sprague Dawley (SD) rats that were either sham irradiated or received fractionated doses (9 Gy per day × 5 days) of targeted X-ray radiation to the heart. Metabolomic and lipidomic analyses were utilized as a correlative approach for delineation of novel biomarkers associated with radiation-induced cardiac toxicity. Additionally, we used high-resolution mass spectrometry to examine the metabolomic profiles of plasma samples obtained from patients receiving high dose thoracic RT for esophageal cancer. RESULTS: Metabolic alterations in the rat model and patient plasma profiles, showed commonalities of radiation response that included steroid hormone biosynthesis and vitamin E metabolism. Alterations in patient plasma profiles were used to develop classification algorithms predictive of patients at risk of developing RIHD. CONCLUSION: Herein, we report the feasibility of developing a metabolomics-based biomarker panel that is associated with adverse outcomes of cardiac function in patients who received RT for the treatment of esophageal cancer. PMID: 32360032 [PubMed - as supplied by publisher]

Related Articles Comparative exploration of free fatty acids in donkey colostrum and mature milk based on a metabolomics approach. J Dairy Sci. 2020 Apr 29;: Authors: Li M, Liu Y, Li Q, Yang M, Pi Y, Yang N, Zheng Y, Yue X Abstract Donkey milk is an ideal substitute for human milk owing to its similar composition. Nevertheless, changes in the composition and related metabolic pathways of free fatty acids (FFA) in donkey milk between colostrum and mature milk have not been studied well. In this study, metabolomic methods based on gas chromatography tandem time-of-flight mass spectrometry (GC-TOF-MS) were used to explore and compare FFA in donkey colostrum (DC) and mature milk (DMM). A total of 24 FFA were characterized and quantified in DC and in DMM. Of these, 11 FFA differed significantly between DC and DMM, and there were 6 key differential metabolic pathways. These results demonstrated that the composition of FFA in donkey milk changed with lactation stage. The interactions and metabolic pathways were further analyzed to explore the mechanisms that altered the milk composition during lactation. Our results provide insights into the changes in milk of the nonruminant mammals during lactation. The results provide practical information for the development of donkey milk products and a foundation for future research on specific milk nutrients. PMID: 32359984 [PubMed - as supplied by publisher]

Related Articles Mass Spectrometry Untangles Plant Membrane Protein Signaling Networks. Trends Plant Sci. 2020 Apr 28;: Authors: Chen Y, Weckwerth W Abstract Plasma membranes (PMs) act as primary cellular checkpoints for sensing signals and controlling solute transport. Membrane proteins communicate with intracellular processes through protein interaction networks. Deciphering these signaling networks provides crucial information for elucidating in vivo cellular regulation. Large-scale proteomics enables system-wide characterization of the membrane proteome, identification of ligand-receptor pairs, and elucidation of signals originating at membranes. In this review we assess recent progress in the development of mass spectrometry (MS)-based proteomic pipelines for determining membrane signaling pathways. We focus in particular on current techniques for the analysis of membrane protein phosphorylation and interaction, and how these proteins may be connected to downstream changes in gene expression, metabolism, and physiology. PMID: 32359835 [PubMed - as supplied by publisher]

Related Articles Machine learning, the kidney, and genotype-phenotype analysis. Kidney Int. 2020 Apr 01;: Authors: Sealfon RSG, Mariani LH, Kretzler M, Troyanskaya OG Abstract With biomedical research transitioning into data-rich science, machine learning provides a powerful toolkit for extracting knowledge from large-scale biological data sets. The increasing availability of comprehensive kidney omics compendia (transcriptomics, proteomics, metabolomics, and genome sequencing), as well as other data modalities such as electronic health records, digital nephropathology repositories, and radiology renal images, makes machine learning approaches increasingly essential for analyzing human kidney data sets. Here, we discuss how machine learning approaches can be applied to the study of kidney disease, with a particular focus on how they can be used for understanding the relationship between genotype and phenotype. PMID: 32359808 [PubMed - as supplied by publisher]

Related Articles Metabolic Regulation of Tissue Stem Cells. Trends Cell Biol. 2020 Apr 28;: Authors: Shapira SN, Christofk HR Abstract Adult tissue stem cells mediate organ homeostasis and regeneration and thus are continually making decisions about whether to remain quiescent, proliferate, or differentiate into mature cell types. These decisions often integrate external cues, such as energy balance and the nutritional status of the organism. Metabolic substrates and byproducts that regulate epigenetic and signaling pathways are now appreciated to have instructive rather than bystander roles in regulating cell fate decisions. In this review, we highlight recent literature focused on how metabolites and dietary manipulations can impact cell fate decisions, with a focus on the regulation of adult tissue stem cells. PMID: 32359707 [PubMed - as supplied by publisher]

Related Articles Metabolomic approach to measuring quality of chilled chicken meat during storage. Poult Sci. 2020 May;99(5):2543-2554 Authors: Wen D, Liu Y, Yu Q Abstract The metabolites of stored, chilled chicken meat were analyzed using liquid chromatograph-mass spectrometry and metabolomics. The results showed significant differences in the metabolites of chicken meat stored at 4°C for 0 D and meat stored for longer periods of 2 D, 4 D, 6 D, and 10 D, when analyzed based on a variable of importance >2 and P < 0.05. These changed metabolites included amino acids, amines, nucleosides, nucleotides, carbohydrates, organic acids, and other substances. The data from this study provide a holistic understanding of food quality changes in chicken meat during deterioration in storage. PMID: 32359590 [PubMed - in process]

Related Articles Metabolomics reveals differential mechanisms of toxicity of hyperbranched poly(ethyleneimine)-derived nanoparticles to the soil-borne fungus Verticillium dahliae Kleb. Pestic Biochem Physiol. 2020 May;165:104535 Authors: Lykogianni M, Papadopoulou EA, Sapalidis A, Tsiourvas D, Sideratou Z, Aliferis KA Abstract There is a consensus on the urge for the discovery and assessment of alternative, improved sources of bioactivity that could be developed as plant protection products (PPPs), in order to combat issues that the agrochemical sector is facing. Based on the recent advances in nanotechnology, nanoparticles seem to have a great potential towards the development of the next generation nano-PPPs used as active ingredients (a.i.) per se or as nanocarriers in their formulation. Nonetheless, information on their mode(s)-of-action (MoA) and mechanisms of toxicity is yet largely unknown, representing a bottleneck in their further assessment and development. Therefore, we have undertaken the task to assess the fungitoxicity of hyperbranched poly(ethyleneimine) (HPEI), quaternized hyperbranched poly(ethyleneimine) (QPEI), and guanidinylated hyperbranched poly(ethyleneimine) (GPEI) nanoparticles to the soil-born plant pathogenic fungus Verticillium dahliae Kleb, and dissect their effects on its metabolism applying GC/EI/MS metabolomics. Results revealed that functionalization of HPEI nanoparticles with guanidinium end groups (GPEI) increases their toxicity to V. dahliae, while functionalization with quaternary ammonium end groups (QPEI) decreases it. The treatments with the nanoparticles affected the chemical homeostasis of the fungus, altering substantially its amino acid pool, energy production, and fatty acid content, causing additionally oxidative and osmotic stresses. To the best of our knowledge, this is the first report on the comparative toxicity of HPEI, QPEI, and GPEI to filamentous fungi applying metabolomics. The findings could be exploited in the study of the quantitative structure-activity relationship (QSAR) of HPEI-derived nanoparticles and their further development as nano-PPPs. PMID: 32359556 [PubMed - in process]

Related Articles The yeast (Saccharomyces cerevisiae) YCF1 vacuole transporter: Evidence on its implication into the yeast resistance to flusilazole as revealed by GC/EI/MS metabolomics. Pestic Biochem Physiol. 2020 May;165:104475 Authors: Karamanou DA, Aliferis KA Abstract The development of plant protection product (PPPs)-resistant populations of plant pathogens, pests, and weeds, represents a major challenge that the crop protection sector is facing. Focusing on plant pathogenic fungi, the increased efflux of the active ingredients (a.i.) from the cytoplasm is highly correlated to elevated resistance levels to the applied fungicides. Such mechanism is regulated by ATP-binding cassette transporters (ABC transporters), and although it has been investigated for the past two decades, the latest developments in "omics" technologies could provide new insights with potential applications in crop protection. Within this context, and based on results from preliminary experiments, we have undertaken the task of mining the involvement of the ABC transporter YCF1, which is located in the vacuole membrane, in the fungicide resistance development, applying a functional genomics approach and using yeast (Saccharomyces cerevisiae) as the model organism. Among the fungicides being assessed, flusilazole, which belongs to the azole group of dimethylation inhibitors (DMIs), was discovered as a possible substrate of the YCF1. GC/EI/MS metabolomics analysis revealed the effect of the fungicide's toxicity and that of genotype on yeast's metabolism, confirming the role of this transporter. Fluctuations in the activity of various yeast biosynthetic pathways associated with stress responses were recorded, and corresponding metabolites-biomarkers of flusilazole toxicity were discovered. The metabolites α,α-trehalose, glycerol, myo-inositol-1-phosphate, GABA, l-glutamine, l-tryptophan, l-phenylalanine, l-tyrosine, and phosphate, were the major identified biomarkers of toxicity. Among these, are metabolites that play important roles in fungal metabolism (e.g., cell responses to osmotic stress) or serve as signaling molecules. To the best of our knowledge, this is the first report on the implication of YCF1 in fungal resistance to PPPs. Additionally, the results of GC/EI/MS yeast metabolomics confirmed the robustness of the method and its applicability in the high-throughput study of fungal resistance to fungicides. PMID: 32359550 [PubMed - in process]