PubMed
Neutron-encoded diubiquitins to profile linkage selectivity of deubiquitinating enzymes
Nat Commun. 2023 Mar 25;14(1):1661. doi: 10.1038/s41467-023-37363-6.ABSTRACTDeubiquitinating enzymes are key regulators in the ubiquitin system and an emerging class of drug targets. These proteases disassemble polyubiquitin chains and many deubiquitinases show selectivity for specific polyubiquitin linkages. However, most biochemical insights originate from studies of single diubiquitin linkages in isolation, whereas in cells all linkages coexist. To better mimick this diubiquitin substrate competition, we develop a multiplexed mass spectrometry-based deubiquitinase assay that can probe all ubiquitin linkage types simultaneously to quantify deubiquitinase activity in the presence of all potential diubiquitin substrates. For this, all eight native diubiquitins are generated and each linkage type is designed with a distinct molecular weight by incorporating neutron-encoded amino acids. Overall, 22 deubiquitinases are profiled, providing a three-dimensional overview of deubiquitinase linkage selectivity over time and enzyme concentration.PMID:36966155 | DOI:10.1038/s41467-023-37363-6
Cerebrospinal fluid-based metabolomics and the characterization of brain tumors
Asian J Surg. 2023 Mar 24:S1015-9584(23)00367-6. doi: 10.1016/j.asjsur.2023.03.060. Online ahead of print.NO ABSTRACTPMID:36966106 | DOI:10.1016/j.asjsur.2023.03.060
Untargeted Metabolomics Analysis of Gentamicin-Induced Tolerant Colonies of Klebsiella pneumoniae
Eur J Pharm Sci. 2023 Mar 23:106436. doi: 10.1016/j.ejps.2023.106436. Online ahead of print.ABSTRACTPURPOSE: Antibiotic resistance development in pathogenic bacteria like Klebsiella pneumoniae seriously threatens humankind. Therefore, it is important to understand the interaction of bacteria with antibiotic agents and how it acquires resistance at the molecular level. The current study describes metabolomics analysis of K. pneumoniae sensitive strains and its gentamicin-tolerant (resistant) strains.METHODS: K. pneumoniae strains were treated at five different concentrations of gentamicin, increasing from a low dose (16.2 µg/mL) to the highest dose (250 µg/mL) at three incubation time periods (24h, 48h, and 72h). Colonies obtained at various concentrations and time intervals were subjected to metabolomic analysis using GC-MS.RESULTS: A drastic change was observed in the morphology of K. pneumoniae colonies with the increasing gentamicin concentration. Moreover, K. pneumoniae strains grown at the highest concentration (250 µg/mL) were found tolerant to 1 mg/mL gentamicin (4-folds) and considered resistant strains. A total of 459 metabolites were identified. A sequential down/up-regulation in 4, 3, and 4 metabolites were observed in association with the increasing gentamicin concentration at 24h, 48h, and 72h, respectively. While with the comparative analysis of resistant and sensitive strains, a total of seven down- and sixteen up-regulated metabolites were observed. The concentration of some fatty acids and sugars have been found to increase while, a few metabolites like inosine, tyrosine, 1-propionylproline, and 2-hydroxyacetic acid have been found down-regulated in resistant samples.CONCLUSION: These regulator metabolites might be associated with resistance development in K. pneumoniae against gentamicin and might be helpful in the rapid detection of gentamicin-resistant clinical strains.PMID:36965642 | DOI:10.1016/j.ejps.2023.106436
High-level production of 2-pyrone-4,6-dicarboxylic acid from vanillic acid as a lignin-related aromatic compound by metabolically engineered fermentation to realize industrial valorization processes of lignin
Bioresour Technol. 2023 Mar 23:128956. doi: 10.1016/j.biortech.2023.128956. Online ahead of print.ABSTRACT2-pyrone-4,6-dicarboxylic acid (PDC) is a valuable building block molecule produced from lignin-derived aromatic compounds by biological funneling. This study aimed to design a fermentation process for producing PDC from vanillic acid, which could be applied at an industrial production. Metabolomic analysis revealed that a high primary metabolic activity within cells was required to improve the production efficiency. Moreover, a medium with ammonium salts and no alkali metals was advantageous because it suppressed the formation of PDC-metal complexes. Our optimized process yielded the highest PDC titer and productivity ever reported: 99.9 g/L and 1.69 g/L/h, respectively. Per batch, 190 g of PDC was produced per liter of initial culture media, and the final liquid volume was 1.9 L. Our study demonstrates the design of fermentation processes for the advanced industrial utilization of lignin by biological funneling. (136 words).PMID:36965585 | DOI:10.1016/j.biortech.2023.128956
Reduced energy metabolism contributing to aging of skeletal muscle by serum metabolomics and gut microbiota analysis
Life Sci. 2023 Mar 23:121619. doi: 10.1016/j.lfs.2023.121619. Online ahead of print.ABSTRACTAIMS: Sarcopenia is an age-related syndrome characterized by a gradual loss of the muscle mass, strength, and function. It is associated with a high risk of adverse consequences such as poorer quality of life, falls, disability and mortality among the elderly. The aim in this study is to investigate the pathological mechanism of sarcopenia.MAIN METHODS: The aging of skeletal muscle was investigated by the D-galactose induced accelerated aging model combining with constrained motion. After 10 weeks, muscle function and gastrocnemius muscle index, and morphology of muscle fibers were evaluated, and myostatin, IGF-1 and ATP in skeletal muscle were also determined. Then the mechanism of aging-related skeletal muscle dysfunctions was investigated based on untargeted serum metabolomics and 16S rRNA gene sequencing. Four key metabolites were validated by the D-galactose-induced C2C12 senescent cell model in vitro.KEY FINDINGS: Results showed that gastrocnemius muscle mass was decreased significantly, morphology of muscle fibers was altered, and muscle function was damaged in the aged group. Furthermore, increased MSTN, and decreased IGF-1 and ATP were also observed in the aging skeletal muscle. Importantly, alteration of the key pathways including riboflavin biosynthesis and energy metabolism contributed to the aging of skeletal muscle. Four key metabolites, including riboflavin, α-ketoglutaric acid and two dicarboxylic acids, which were involved in these metabolic pathways, could promote the proliferation of C2C12 cells.SIGNIFICANCE: These findings provide novel insights into pathological mechanism of sarcopenia, and will facilitate the development of therapeutic and preventive strategies for sarcopenia.PMID:36965523 | DOI:10.1016/j.lfs.2023.121619
Chronic sleep loss sensitizes Drosophila melanogaster to nitrogen stress
Curr Biol. 2023 Mar 20:S0960-9822(23)00296-8. doi: 10.1016/j.cub.2023.03.008. Online ahead of print.ABSTRACTChronic sleep loss profoundly impacts metabolic health and shortens lifespan, but studies of the mechanisms involved have focused largely on acute sleep deprivation.1,2 To identify metabolic consequences of chronically reduced sleep, we conducted unbiased metabolomics on heads of three adult Drosophila short-sleeping mutants with very different mechanisms of sleep loss: fumin (fmn), redeye (rye), and sleepless (sss).3,4,5,6,7 Common features included elevated ornithine and polyamines, with lipid, acyl-carnitine, and TCA cycle changes suggesting mitochondrial dysfunction. Studies of excretion demonstrate inefficient nitrogen elimination in adult sleep mutants, likely contributing to their polyamine accumulation. Increasing levels of polyamines, particularly putrescine, promote sleep in control flies but poison sleep mutants. This parallels the broadly enhanced toxicity of high dietary nitrogen load from protein in chronically sleep-restricted Drosophila, including both sleep mutants and flies with hyper-activated wake-promoting neurons. Together, our results implicate nitrogen stress as a novel mechanism linking chronic sleep loss to adverse health outcomes-and perhaps for linking food and sleep homeostasis at the cellular level in healthy organisms.PMID:36965479 | DOI:10.1016/j.cub.2023.03.008
Sulfide causes histological damage, oxidative stress, metabolic disorders and gut microbiota dysbiosis in juvenile sea cucumber Apostichopus japonicus Selenka
Aquat Toxicol. 2023 Feb 26;258:106439. doi: 10.1016/j.aquatox.2023.106439. Online ahead of print.ABSTRACTSulfide is a common harmful substance in sediments, with an especially high risk for deposit feeder organisms. The sea cucumber Apostichopus japonicus is a typical benthic feeder, and its intestine is the first line of defense and serves as a crucial barrier function. In this study, histological, physiological, gut microbiota, and metabolomic analyses were performed to explore the toxic response in the intestine of juvenile A. japonicus exposed to 0, 0.8, and 1.6 mg/L sulfide stress for 96 h. The results revealed sulfide-induced intestinal inflammatory symptoms and oxidative stress. Moreover, gut bacterial composition was observed after sulfide exposure, with an increase in Proteobacteria and a decrease in Cyanobacteria and Planctomycetes. Specifically, sulfide increased a set of sulfide-removing bacteria and opportunistic pathogens while decreasing several putative beneficial substance-producing bacteria. The metabolomic analysis indicated that sulfide also disturbed metabolic homeostasis, especially lipid and energy metabolism, in intestine. Interestingly, several intestinal bacteria were further identified to be significantly correlated with metabolic changes; for example, the decreased abundance levels of Bacillus, Corynebacterium, and Psychromonas were positively correlated with important energy metabolites, including maleic acid, farnesyl pyrophosphate, thiamine, butynoic acid, and deoxycholic acid. Thus, our research provides new insights into the mechanisms associated with the intestinal metabolic and microbiota response involved in sulfide stress adaptation strategies of juvenile A. japonicus.PMID:36965428 | DOI:10.1016/j.aquatox.2023.106439
Determination of creatinine in urine and blood serum human samples by CZE-UV using on-column internal standard injection
Talanta. 2023 Mar 21;258:124465. doi: 10.1016/j.talanta.2023.124465. Online ahead of print.ABSTRACTCreatinine is a well-stablished biomarker for kidney malfunctions and for normalization parameter of urinary quantitative information. Recently, metabolic studies have been discovering other functionalities for creatinine tests in human urine and blood serum. In this work we present an enhanced capillary electrophoresis (CE) based protocol for determination of creatinine. CE is a high-throughput separation technique that have been getting attention through the last decades and might be considered to be adopted as an analytical instrumentation for clinical purposes. In the proposed method, we performed a short injection program with on-column addition of internal standard. Additionally, the method allows a simultaneous screening of non-proteinogenic amino acids that could be considered for metabolomics purposes. We design a pilot study that successfully estimated the creatinine value in 100 urine samples with (2.85 ± 1.78) mg dL-1 LOD; (8.24 ± 5.93) mg dL-1 LOQ and 82.4% accuracy. Considering that serum creatinine is also included in the clinical laboratory routines for estimated Glomerular Filtration Rate dosage, the method was complementary applied to 10 blood serum samples, which resulted in a model with (0.4 ± 0.2) mg dL-1 LOD; (2.0 ± 0.6) mg dL-1 LOQ and 83.8% of accuracy. All results were in agreement with reference values. The proposed method promotes a great analytical frequency and reproducibility with enhanced specificity compared with the ongoing protocol by Jaffe's reaction, thereby proving to be useful as an alternative for creatinine exams that might help complete a diagnosis of a series of health-related issues.PMID:36965416 | DOI:10.1016/j.talanta.2023.124465
Metabolite fingerprinting of the ripening process in Pixian douban using a feature-based molecular network and metabolomics analysis
Food Chem. 2023 Mar 20;418:135940. doi: 10.1016/j.foodchem.2023.135940. Online ahead of print.ABSTRACTThe unique flavor of Pixian douban (PXDB) is widely acknowledged to be associated with its maturation process. However, there is limited knowledge about the non-volatile metabolites that contribute to this flavor. To bridge this gap, this study employed a metabolomics approach and a feature-based molecular network (FBMN) analysis to investigate the non-volatile metabolite fingerprints of PXDB during its two-year maturation process. Specifically, the FBMN tool was utilized to annotate the flavonoid, amide derivatives, and lipid components of PXDB for the first time. Subsequently, the MolNetEnhancer tool was employed to complement the FBMN annotation and identify eight substructural components. Finally, metabolomics analysis was carried out to identify 45 key metabolites involved in flavor formation across 10 major metabolic pathways (p < 0.05). Overall, the findings of this study have significantly expanded our understanding of the non-volatile metabolite fingerprinting and flavor formation mechanisms.PMID:36965392 | DOI:10.1016/j.foodchem.2023.135940
Metabolomics and chemometrics depict the changes in the chemical profile of white lupine (Lupinus albus L.) bioactive metabolites during seed germination
Food Chem. 2023 Mar 21;418:135967. doi: 10.1016/j.foodchem.2023.135967. Online ahead of print.ABSTRACTThe current study attempts to illustrate how the chemical and biological profile of white lupine seeds varies throughout the course of various germination days using UHPLC-QqQ-MS combined to chemometrics. Abscisic acid showed maximum level in the un-germinated seeds and started to decline with seed germination accompanied by an increase in the levels of gibberellins which were undetectable in un-germinated seeds. Coumaronochromones were the most prevalent constituents detected in un-germinated seeds while day 2 sprouts showed significant accumulation of flavones. The levels of alkaloids showed significant increase upon germination of the seeds reaching its maximum in day 14 sprouts. The OPLS model coefficients plot indicated that lupinalbin D and F, apigenin hexoside, kaempferol hexoside, albine, and hydoxylupanine showed strong positive correlation to the alpha amylase inhibitory activity of the tested samples while lupinalbin A, lupinisoflavone, lupinic acid and multiflorine were positively correlated to the inhibition of alpha glycosidase activity. The results obtained indicated that seed germination has a profound effect on the chemical profile as well as the in-vitro antidiabetic activity of lupine seeds.PMID:36965385 | DOI:10.1016/j.foodchem.2023.135967
Description of two cultivated and two uncultivated new Salinibacter species, one named following the rules of the bacteriological code: Salinibacter grassmerensis sp. nov.; and three named following the rules of the SeqCode: Salinibacter pepae sp. nov....
Syst Appl Microbiol. 2023 Mar 15;46(3):126416. doi: 10.1016/j.syapm.2023.126416. Online ahead of print.ABSTRACTCurrent -omics methods allow the collection of a large amount of information that helps in describing the microbial diversity in nature. Here, and as a result of a culturomic approach that rendered the collection of thousands of isolates from 5 different hypersaline sites (in Spain, USA and New Zealand), we obtained 21 strains that represent two new Salinibacter species. For these species we propose the names Salinibacter pepae sp. nov. and Salinibacter grassmerensis sp. nov. (showing average nucleotide identity (ANI) values < 95.09% and 87.08% with Sal. ruber M31T, respectively). Metabolomics revealed species-specific discriminative profiles. Sal. ruber strains were distinguished by a higher percentage of polyunsaturated fatty acids and specific N-functionalized fatty acids; and Sal. altiplanensis was distinguished by an increased number of glycosylated molecules. Based on sequence characteristics and inferred phenotype of metagenome-assembled genomes (MAGs), we describe two new members of the genus Salinibacter. These species dominated in different sites and always coexisted with Sal. ruber and Sal. pepae. Based on the MAGs from three Argentinian lakes in the Pampa region of Argentina and the MAG of the Romanian lake Fără Fund, we describe the species Salinibacter pampae sp. nov. and Salinibacter abyssi sp. nov. respectively (showing ANI values 90.94% and 91.48% with Sal. ruber M31T, respectively). Sal. grassmerensis sp. nov. name was formed according to the rules of the International Code for Nomenclature of Prokaryotes (ICNP), and Sal. pepae, Sal. pampae sp. nov. and Sal. abyssi sp. nov. are proposed following the rules of the newly published Code of Nomenclature of Prokaryotes Described from Sequence Data (SeqCode). This work constitutes an example on how classification under ICNP and SeqCode can coexist, and how the official naming a cultivated organism for which the deposit in public repositories is difficult finds an intermediate solution.PMID:36965279 | DOI:10.1016/j.syapm.2023.126416
Quality assessment of Astragali Radix based on pseudo-targeted metabolomics and chemometric approach
J Sep Sci. 2023 Mar 25:e2200985. doi: 10.1002/jssc.202200985. Online ahead of print.ABSTRACTAstragali Radix is widely used because of its dual use in medicine and food, and its quality evaluation is of great importance. In this study, a pseudo-targeted metabolomics approach based on scheduled multiple reaction monitoring was developed, and a total of 114 compounds with good linearity, sensitivity and reproducibility were selected for relative quantification, and the chemical differences between Astragali Radix of different growth patterns were further compared by chemometric analysis. With the help of multivariate and univariate analysis, 26 differential compounds between wild/semi-wild Astragali Radix and cultivated Astragali Radix were determined. Then 5 marker compounds were screened out by lasso regression, and further verified by systematic clustering, random forest, support vector machine, and logistic regression. In addition, malonyl-substituted flavonoids showed relatively higher content in wild/semi-wild Astragali Radix. Thus, the malonyl-substitution was the characteristic for flavonoids in wild/semi-wild Astragali Radix. In conclusion, the application of pseudo-targeted metabolomics and various statistical methods could offer multi-dimensional information for the holistic quality evaluation of Astragali Radix. This article is protected by copyright. All rights reserved.PMID:36965089 | DOI:10.1002/jssc.202200985
Combining QTL mapping with multiomics profiling reveals genetic control of corn leaf aphid (Rhopalosiphum maidis) resistance in maize
J Exp Bot. 2023 Mar 25:erad113. doi: 10.1093/jxb/erad113. Online ahead of print.ABSTRACTCorn leaf aphid (Rhopalosiphum maidis) is a major maize pest, frequently causing substantial yield losses. Exploring the genetic basis of aphid resistance is important for improving maize yield and quality. Here, we used a maize recombinant inbred line population derived from two parents with different susceptibility to aphids, B73 (susceptible) and Abe2 (resistant), and performed quantitative trait locus (QTL) mapping using aphid resistance scores as an indicator. We mapped a stable QTL, qRTA6, to chromosome 6 using data from two years' field trials, which explained 40.12%-55.17% of the phenotypic variation. To further investigate the mechanism of aphid resistance in Abe2, we constructed transcriptome and metabolome libraries from Abe2 and B73 leaves with or without aphid infestation at different time points (0, 6 and 24h). Integrating QTL mapping and transcriptome data revealed three aphid resistance candidate genes (Zm00001d035736, Zm00001d035751, and Zm00001d035767) associated with the hypersensitive response, the jasmonic acid pathway and protein ubiquitination. Integrated transcriptomic and metabolomic analysis revealed that the differentially expressed genes and metabolites were enriched in flavonoid biosynthesis. These findings extend our understanding of the molecular mechanisms controlling aphid resistance, and the QTL and candidate genes are valuable resources for increasing aphid resistance in maize.PMID:36964900 | DOI:10.1093/jxb/erad113
Characterization and metabolomic profiling of two pigment producing fungi from infected fruits of Indian Gooseberry
Arch Microbiol. 2023 Mar 25;205(4):141. doi: 10.1007/s00203-023-03483-2.ABSTRACTTwo pigment producing fungi, Talaromyces atroroseus and Penicillium choerospondiatis, were isolated and identified from infected fruits of Phyllanthus emblica L. based on amplification and sequencing of internal transcribed spacer region and beta-tubulin gene. This is the first occurrence report of these two fungi from fruits of P. emblica. Culture extract containing metabolites of T. atroroseus and P. choerospondiatis contained phenolics of 26.35 mg and 30.89 mg GAE/g dry extract respectively; whereas no significant amount of flavonoids and tannins were detected. P. choerospondiatis metabolites extract showed higher DPPH and ABTS activity with IC50 values of 21.94 mg/ml and 27.03 mg/ml respectively than T. atroroseus. LC-HRMS analysis of metabolites extract of T. atroroseus revealed presence of trimethyl-isopropyl-butanamide, perlolyrine, N-hexadecanoylpyrrolidine etc. whereas P. choerospondiatis displayed presence of tangeraxanthin, ugaxanthone, daphniphylline, etc. Therefore, fungal metabolites are rich natural sources of diversified compounds that can be utilized in dyeing industries, cosmetics and novel drug development.PMID:36964798 | DOI:10.1007/s00203-023-03483-2
No skin off your back: the sampling and extraction of sebum for metabolomics
Metabolomics. 2023 Mar 24;19(4):21. doi: 10.1007/s11306-023-01982-3.ABSTRACTINTRODUCTION: Sebum-based metabolomics (a subset of "sebomics") is a developing field that involves the sampling, identification, and quantification of metabolites found in human sebum. Sebum is a lipid-rich oily substance secreted by the sebaceous glands onto the skin surface for skin homeostasis, lubrication, thermoregulation, and environmental protection. Interest in sebomics has grown over the last decade due to its potential for rapid analysis following non-invasive sampling for a range of clinical and environmental applications.OBJECTIVES: To provide an overview of various sebum sampling techniques with their associated challenges. To evaluate applications of sebum for clinical research, drug monitoring, and human biomonitoring. To provide a commentary of the opportunities of using sebum as a diagnostic biofluid in the future.METHODS: Bibliometric analyses of selected keywords regarding skin surface analysis using the Scopus search engine from 1960 to 2022 was performed on 12th January 2023. The published literature was compartmentalised based on what the work contributed to in the following areas: the understanding about sebum, its composition, the analytical technologies used, or the purpose of use of sebum. The findings were summarised in this review.RESULTS: Historically, about 15 methods of sampling have been used for sebum collection. The sample preparation approaches vary depending on the analytes of interest and are summarised. The use of sebum is not limited to just skin diseases or drug monitoring but also demonstrated for other systemic disease. Most of the work carried out for untargeted analysis of metabolites associated with sebum has been in the recent two decades.CONCLUSION: Sebum has a huge potential beyond skin research and understanding how one's physiological state affects or reflects on the skin metabolome via the sebaceous glands itself or by interactions with sebaceous secretion, will open doors for simpler biomonitoring. Sebum acts as a sink to environmental metabolites and has applications awaiting to be explored, such as biosecurity, cross-border migration, localised exposure to harmful substances, and high-throughput population screening. These applications will be possible with rapid advances in volatile headspace and lipidomics method development as well as the ability of the metabolomics community to annotate unknown species better. A key issue with skin surface analysis that remains unsolved is attributing the source of the metabolites found on the skin surface before meaningful biological interpretation.PMID:36964290 | DOI:10.1007/s11306-023-01982-3
Feature impact assessment: a new score to identify relevant metabolomics features in artificial neural networks using validated labels
Metabolomics. 2023 Mar 25;19(4):22. doi: 10.1007/s11306-023-01996-x.ABSTRACTINTRODUCTION: Artificial Neural Networks (ANN) are increasingly used in metabolomics but are hard to interpret.OBJECTIVES: We aimed at developing a feature impact score that is model-agnostic, simple, and interpretable.METHODS: Feature Impact Assessment (FIA) is calculated by varying combinations of features within their observed value range and checking for changes in prediction outcomes. FIA was implemented in R and tested on metabolomics datasets.RESULTS: FIA exceeded LIME and SHAP in selecting biologically meaningful features. Values were comparable across different ANN architectures.CONCLUSION: FIA is a novel score ranking feature impact, helping interpreting ANN in the metabolomics field.PMID:36964272 | DOI:10.1007/s11306-023-01996-x
Associations between per- and polyfluoroalkyl substances (PFAS) and diabetes in two population-based cohort studies from Sweden
J Expo Sci Environ Epidemiol. 2023 Mar 24. doi: 10.1038/s41370-023-00529-x. Online ahead of print.ABSTRACTBACKGROUND: Per- and polyfluoroalkyl substances (PFAS) have been suggested to contribute to the development of metabolic diseases such as obesity, diabetes and non-alcoholic fatty liver disease (NAFLD). However, evidence from epidemiological studies remain divergent. The aim of the present study was to evaluate associations between PFAS exposure and prevalent diabetes in a cross-sectional analysis and fasting glucose in a longitudinal analysis.METHODS: In 2373 subjects aged 45-75 years from the EpiHealth study, three PFAS; perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) were analyzed in plasma together with information on prevalent diabetes. Participants in the PIVUS study (n = 1016 at baseline, all aged 70 years) were followed over 10 years regarding changes in plasma levels of six PFAS; PFHxS, PFOA, PFOS, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), and changes in plasma levels of fasting glucose.RESULTS: In the EpiHealth study, no overall associations could be observed between the levels of PFOA, PFOS or PFHxS and prevalent diabetes. However, there was a significant sex-interaction for PFOA (p = 0.02), and an inverse association could be seen between PFOA (on a SD-scale) and prevalent diabetes in women only (OR: 0.71, 95% CI: 0.52, 0.96, p-value: 0.02). This association showed a non-monotonic dose-response curve. In the PIVUS study, inverse relationships could be observed between the changes in levels (ln-transformed) of PFOA and PFUnDA vs the change in fasting glucose levels (ln-transformed) over 10 years (p = 0.04 and p = 0.02, respectively). As in EpiHealth, these inverse associations were significant only in women (PFOA: β: -0.03, p = 0.02, PFUnDA: β: -0.03, p = 0.03).IMPACT: Exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to unfavorable human health, including metabolic disorders such as obesity, diabetes and non-alcoholic fatty liver disease. However, results from in vivo, in vitro and epidemiological studies are incoherent. The aim of the present study was therefore to investigate associations between PFAS and diabetes in a cross-sectional study and glucose levels in a longitudinal study. Results show inverse associations in women only. Results also display non-monotonic dose response curves (i.e., that only low levels of PFOA are related to higher probability of prevalent diabetes). This suggests that sex differences and complex molecular mechanisms may underlie the observed findings. A better understanding of the factors and molecular mechanisms contributing to such differences is recognized as an important direction for future research.CONCLUSIONS: PFOA was found to be inversely related to both prevalent diabetes and changes in plasma glucose levels among women only. Thus, our findings suggest there are sex differences in the inverse relationship of PFOA and type 2 diabetes and glucose levels.PMID:36964247 | DOI:10.1038/s41370-023-00529-x
The core metabolome and root exudation dynamics of three phylogenetically distinct plant species
Nat Commun. 2023 Mar 24;14(1):1649. doi: 10.1038/s41467-023-37164-x.ABSTRACTRoot exudates are plant-derived, exported metabolites likely shaping root-associated microbiomes by acting as nutrients and signals. However, root exudation dynamics are unclear and thus also, if changes in exudation are reflected in changes in microbiome structure. Here, we assess commonalities and differences between exudates of different plant species, diurnal exudation dynamics, as well as the accompanying methodological aspects of exudate sampling. We find that exudates should be collected for hours rather than days as many metabolite abundances saturate over time. Plant growth in sterile, nonsterile, or sugar-supplemented environments significantly alters exudate profiles. A comparison of Arabidopsis thaliana, Brachypodium distachyon, and Medicago truncatula shoot, root, and root exudate metabolite profiles reveals clear differences between these species, but also a core metabolome for tissues and exudates. Exudate profiles also exhibit a diurnal signature. These findings add to the methodological and conceptual groundwork for future exudate studies to improve understanding of plant-microbe interactions.PMID:36964135 | DOI:10.1038/s41467-023-37164-x
Metabolomics of the interaction between a consortium of entomopathogenic fungi and their target insect: Mechanisms of attack and survival
Pestic Biochem Physiol. 2023 Apr;191:105369. doi: 10.1016/j.pestbp.2023.105369. Epub 2023 Feb 12.ABSTRACTOne of the most concerning pests that attack strawberries in Brazil is Duponchelia fovealis (Zeller), a non-native moth with no registered control methods to date. Our group recently observed that a fungal consortium formed by two strains of Beauveria bassiana (Balsamo) increased the mortality of D. fovealis more than inoculation with each strain on its own. However, the molecular interaction between the fungal consortium and the caterpillars is unknown. Thus, in this work, we sought to pioneer the evaluation of the molecular interaction between a fungal consortium of B. bassiana and D. fovealis caterpillars. We aimed to understand the biocontrol process involved in this interaction and the defense system of the caterpillar. Seven days after D. fovealis were inoculated with the consortium, the dead and surviving caterpillars were analyzed using GC-MS and LC-MS. Some of the metabolites identified in dead caterpillars have primarily antioxidant action. Other metabolites may have insecticidal potential, such as diltiazem-like and tamsulosin-like compounds, as well as 2,5-dimethoxymandelic acid. In surviving caterpillars, the main mechanisms are pro-inflammatory from 2-Palmitoylglycerol metabolite and the antifungal action of the metabolite Aegle marmelos Alkaloid-C. The metabolites identified in dead caterpillars may explain the increased mortality caused by the consortium due to its antioxidant mechanism, which can suppress the caterpillars' immune system, and insecticide action. In surviving caterpillars, the main resistance mechanisms may involve the stimulus to the immunity and antifungal action.PMID:36963938 | DOI:10.1016/j.pestbp.2023.105369
Beans comsumption can contribute to the prevention of cardiovascular disease
Clin Nutr ESPEN. 2023 Apr;54:73-80. doi: 10.1016/j.clnesp.2023.01.007. Epub 2023 Jan 12.ABSTRACTCardiovascular diseases (CVD) are the major cause of global mortality, accounting for 31% of deaths worldwide. Healthy eating habits based on the consumption of bioactive molecules present in plant-based diets can contribute to the prevention of CVD. In this context, the consumption of common beans (Phaseolus vulgaris L.) is relevant. There are several species of beans, all of which provide proteins, carbohydrates, dietary fiber, vitamins, minerals, and phenolic compounds. More recently, the complexity of phytochemical components has expanded, including the role of antinutritional factors in nutrient bioavailability and immune responses. Experimental and clinical studies have shown that the consumption of beans results in less food consumption, control of body weight, and improvement of metabolic biochemical parameters. Thus, the consumption of beans is associated with a decrease in CVD risk factors. To date, there have been no interventional studies assessing CVD outcomes, such as hospitalization, infarction, and mortality, in the context of bean consumption. Furthermore, studies on the effect of bean consumption on metabolomics and intestinal microbiota are lacking. The purpose of this review is to explore the nutritional properties of beans and discuss the main effects of the consumption of beans on cardiovascular health. In conclusion, eating habits based on the consumption of bioactive molecules present in beans can contribute to the prevention of cardiovascular disease. Furthermore, there is a large gap in the literature regarding the consumption of beans associated with clinical outcomes, such as hospitalization and mortality.PMID:36963901 | DOI:10.1016/j.clnesp.2023.01.007