Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Targeted metabolomics detects a putatively diagnostic signature in plasma and dried blood spots from head and neck paraganglioma patients

Sat, 25/02/2023 - 12:00
Oncogenesis. 2023 Feb 25;12(1):10. doi: 10.1038/s41389-023-00456-4.ABSTRACTHead and neck paragangliomas (HNPGLs), rare chemoresistant tumors curable only with surgery, are strongly influenced by genetic predisposition, hence patients and relatives require lifetime follow-up with MRI and/or PET-CT because of de novo disease risk. This entails exposure to electromagnetic/ionizing radiation, costs, and organizational challenges, because patients and relatives are scattered far from reference centers. Simplified first-line screening strategies are needed. We employed flow injection analysis tandem mass spectrometry, as used in newborn metabolic screening, to compare the plasma metabolic profile of HNPGL patients (59 samples, 56 cases) and healthy controls (24 samples, 24 cases). Principal Component Analysis (PCA) and Partial Least Discriminant Analysis (PLS-DA) highlighted a distinctive HNPGL signature, likely reflecting the anaplerotic conversion of the TCA cycle to glutaminolysis and catabolism of branched amino acids, DNA damage and deoxyadenosine (dAdo) accumulation, impairment of fatty acid oxidation, switch towards the Warburg effect and proinflammatory lysophosphatidylcholines (LPCs) signaling. Statistical analysis of the metabolites that most impacted on PLS-DA was extended to 10 acoustic neuroma and 2 cholesteatoma patients, confirming significant differences relative to the HNPGL plasma metabolomic profile. The best confusion matrix from the ROC curve built on 2 metabolites, dAdo and C26:0-LPC, provided specificity of 94.29% and sensitivity of 89.29%, with positive and negative predictive values of 96.2% and 84.6%, respectively. Analysis of dAdo and C26:0-LPC levels in dried venous and capillary blood confirmed that dAdo, likely deriving from 2'-deoxy-ATP accumulated in HNPGL cells following endogenous genotoxic damage, efficiently discriminated HNPGL patients from healthy controls and acoustic neuroma/cholesteatoma patients on easily manageable dried blood spots.PMID:36841802 | DOI:10.1038/s41389-023-00456-4

The Gut Microbial Bile Acid Modulation and its Relevance to Digestive Health and Diseases

Sat, 25/02/2023 - 12:00
Gastroenterology. 2023 Feb 23:S0016-5085(23)00161-0. doi: 10.1053/j.gastro.2023.02.022. Online ahead of print.ABSTRACTThe human gut microbiome has been linked to numerous digestive disorders, but its metabolic products have been much less well characterized, in part due to the expense of untargeted metabolomics and in part to the lack of ability to process the data. In this Review, we focus on the rapidly expanding information about the bile acid repertoire produced by the gut microbiome, including the impacts of bile acids on a wide range of host physiological processes and diseases, while also discussing the role of short-chain fatty acids and other important gut microbiome-derived metabolites. Of particular note is the action of gut microbiome-derived metabolites throughout the body, impacting processes ranging from obesity to aging to disorders traditionally thought of as diseases of the nervous system but now being recognized as being strongly influenced by the gut microbiome and the metabolites it produces. We also highlight the emerging role for modifying the gut microbiome to improve health or to treat disease, including the "engineered native bacteria'' approach that takes bacterial strains from a patient, modifies them to alter metabolism, and re-introduces them. Taken together, study of the metabolites derived from the gut microbiome will provide insights into a wide range of physiological and pathophysiological processes, and has substantial potential for new approaches to diagnostics and therapeutics of disease of or involving the gastrointestinal tract.PMID:36841488 | DOI:10.1053/j.gastro.2023.02.022

Mechanism and security of UV driven sodium percarbonate for sulfamethoxazole degradation using DFT and metabolomic analysis

Sat, 25/02/2023 - 12:00
Environ Pollut. 2023 Feb 23:121352. doi: 10.1016/j.envpol.2023.121352. Online ahead of print.ABSTRACTRecently, sodium percarbonate (SPC) as a solid substitute for H2O2 has aroused extensive attention in advanced oxidation processes. In current work, the degradation kinetics and mechanisms of antibiotic sulfamethoxazole (SMX) by ultraviolet (UV) driven SPC system were explored. The removal efficiency of SMX was enhanced as the increasing dosage of SPC. Moreover, hydroxyl radical (•OH), carbonate radical (CO3•-) and superoxide radical (O2•-) were verified to be presented by scavenger experiments and •OH, CO3•- exhibited a significant role in SMX degradation. Reactions mediated by these radicals were affected by anions and natural organic matters, implying that an incomplete mineralization of SMX would be ubiquitous. The screening four intermediates and transformation patterns of SMX were verified by DFT analysis. Metabolomic analysis demonstrated that a decreasing negative effect in E. coli after 24 h exposure was induced by intermediates products. In detail, SMX interfered in some key functional metabolic pathways including carbohydrate metabolism, pentose and glucuronate metabolism, nucleotide metabolism, arginine and proline metabolism, sphingolipid metabolism, which were mitigated after UV/SPC oxidation treatment, suggesting a declining environmental risk of SMX. This work provided new insights into biological impacts of SMX and its transformation products and vital guidance for SMX pollution control using UV/SPC technology.PMID:36841421 | DOI:10.1016/j.envpol.2023.121352

Polyunsaturated fatty acids drive neutrophil extracellular trap formation in nonalcoholic steatohepatitis

Sat, 25/02/2023 - 12:00
Eur J Pharmacol. 2023 Feb 23:175618. doi: 10.1016/j.ejphar.2023.175618. Online ahead of print.ABSTRACTNon-alcoholic steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome. Non-resolving inflammation, triggered by sustained accumulation of lipids, is an important driving force of NASH. Thus, unveiling metabolic immune regulation could help better understand the pathology and intervention of NASH. In this study, we found the recruitment of neutrophils is an early inflammatory event in NASH mice, following the formation of neutrophil extracellular traps (NETs). NET is an initiating factor which exacerbates inflammatory responses in macrophages. Inhibition of NETs using DNase I significantly alleviated inflammation in NASH mice. We further carried out a metabolomic study to identify possible metabolic triggers of NETs, and linoleic acid (LA) metabolic pathway was the most altered pathway. We re-analyzed published clinical data and validated that LA metabolism was highly correlated with NASH. Consistently, both LA and γ-linolenic acid (GLA) were active in triggering NETs formation by oxidative burst. Furthermore, we identified silybin, a hepatoprotective agent, as a potent NETosis inhibitor, which effectively blocked NETs formation both in vitro and in vivo. Together, this study not only provide new insights into metabolism-immune causal link in NASH progression, but also demonstrate silybin as an important inhibitor of NETs and its therapeutical potential in treating NETosis-related diseases.PMID:36841284 | DOI:10.1016/j.ejphar.2023.175618

Biostimulation of Salicornia europaea L. crops with plant-growth-promoting bacteria in laboratory and field conditions: effects on growth and metabolite profile

Sat, 25/02/2023 - 12:00
J Appl Microbiol. 2023 Feb 25:lxad036. doi: 10.1093/jambio/lxad036. Online ahead of print.ABSTRACTAIM: The objective of the work was to assess the effect of biostimulation with selected plant growth-promoting bacteria on growth and metabolite profile of Salicornia europaea.METHODS AND RESULTS: S. europaea seeds were inoculated with different combinations of plant growth-promoting bacteria Brevibacterium casei EB3, Pseudomonas oryzihabitans RL18 and Bacillus aryabhattai SP20. Plants germinated from inoculated seeds were grown either in laboratory conditions or in a saline crop field. Fresh and dry weight were determined at the end of the experiment, for biomass quantification. The microbiological quality of fresh shoots for human consumption as salad greens was assessed, and the persistence of the inoculated strains in the plant rhizosphere was confirmed by next-generation sequencing (Illumina) of the 16S rDNA gene. The primary metabolite profile of biostimulated plants was characterized by GC-TOF-MS.In laboratory conditions, inoculation with the two strains B. casei EB3 and P. oryzihabitans RL18 caused the most significant increase in biomass production (fresh and dry weight), and caused a shift in the central metabolic pathways of inoculated plants towards amino acid biosynthesis. In the field experiment, no significant biostimulation effect was detected with any of the tested inoculants. Seed inoculation had no significant effect on the microbiological quality of the edible parts. The persistence of inoculants was confirmed in both experiments.CONCLUSIONS: Manipulation of the plant microbiome can trigger primary metabolic reconfiguration and modulate the plant metabolism while promoting plant growth.PMID:36841232 | DOI:10.1093/jambio/lxad036

Microplastics trigger the Matthew effect on nitrogen assimilation in marine diatoms at an environmentally relevant concentration

Sat, 25/02/2023 - 12:00
Water Res. 2023 Feb 21;233:119762. doi: 10.1016/j.watres.2023.119762. Online ahead of print.ABSTRACTMicroplastics (MPs, diameter <5 mm) are widely distributed on Earth, especially in the oceans. Diatoms account for ∼40% of marine primary productivity and affect the global biogeochemical cycles of macroelements. However, the effects of MPs on marine nitrogen cycling remain poorly understood, particularly comparisons between nitrogen-replete and nitrogen-limited conditions. We found that MPs trigger the Matthew effect on nitrogen assimilation in diatoms, where MPs inhibited nitrogen assimilation under nitrogen-limited conditions while enhancing nitrogen metabolism under nitrogen-replete conditions in Phaeodactylum tricornutum. Nitrate reductase (NR) and nitrite reductase (NIR) are upregulated, but nitrate transporter (NRT) and glutamine synthetase (GS) are downregulated by MPs under nitrogen-limited conditions. In contrast, NR, NIR, and GS are all upregulated by MPs under nitrogen-replete conditions. MPs accelerate nitrogen anabolic processes with an increase in the accumulation of carbohydrates by 80.7 ± 7.9% and enhance the activities of key nitrogen-metabolizing enzymes (8.20-44.90%) under nitrogen-replete conditions. In contrast, the abundance of carbohydrates decreases by 22.0-34.4%, and NRT activity is inhibited by 79.0-86.5% in nitrogen-limited algae exposed to MPs. Metabolomic and transcriptomic analyses were performed to further explore the molecular mechanisms of reprogrammed nitrogen assimilation, including carbon metabolism, nitrogen transport and ammonia assimilation. The aforementioned spatial redistribution (e.g., the Matthew effect between nitrogen-replete and -limited conditions) of nitrogen assimilation highlights the potential risks of MP contamination in the ocean.PMID:36841163 | DOI:10.1016/j.watres.2023.119762

Daphnia magna sub-lethal exposure to phthalate pollutants elicits disruptions in amino acid and energy metabolism

Sat, 25/02/2023 - 12:00
Aquat Toxicol. 2023 Feb 23;257:106432. doi: 10.1016/j.aquatox.2023.106432. Online ahead of print.ABSTRACTPhthalic acid esters (PAEs) are a class of chemicals that are usually incorporated as additives in the manufacturing of plastics. PAEs are not covalently bound to the material matrix and can, consequently, be leached into the environment. PAEs have been reported to act as endocrine disruptors, neurotoxins, metabolic stressors, and immunotoxins to aquatic organisms but there is a lack of information regarding the impact of sub-lethal concentrations to target organisms. The freshwater crustacean Daphnia magna, a commonly used model organism in aquatic toxicity, was exposed to four phthalate pollutants: dimethyl phthalate (DMP), diethyl phthalate (DEP), monomethyl phthalate (MMP), and monoethyl phthalate (MEP). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed in a targeted metabolomic approach to quantify polar metabolites extracted from a single Daphnia body. Individual metabolite percent changes and hierarchical clustering heatmap analysis showed unique metabolic profiles for each phthalate pollutant. Metabolite percent changes were mostly downregulated or presented opposing responses for the low and high concentrations tested. Meanwhile, pathway analyses suggest the disruption of related and unique pathways, mostly connected with amino acid and energy metabolism. The pathways aminoacyl-tRNA biosynthesis, arginine biosynthesis, and glutathione metabolism were disrupted by most selected PAEs. Overall, this study indicates that although phthalate pollutants can elicit distinct metabolic perturbations to each PAE, they still impacted related biochemical pathways. These chemical-class based responses could be associated with a common toxic mechanism of action. The reported findings show how targeted metabolomic approaches can lead to a better understanding of sub-lethal exposure to pollutants, revealing metabolomic endpoints do not hold a close relationship with traditional acute toxicity endpoints.PMID:36841068 | DOI:10.1016/j.aquatox.2023.106432

Implementation of effect biomarkers in human biomonitoring studies: A systematic approach synergizing toxicological and epidemiological knowledge

Sat, 25/02/2023 - 12:00
Int J Hyg Environ Health. 2023 Feb 23;249:114140. doi: 10.1016/j.ijheh.2023.114140. Online ahead of print.ABSTRACTHuman biomonitoring (HBM) studies have highlighted widespread daily exposure to environmental chemicals. Some of these are suspected to contribute to adverse health outcomes such as reproductive, neurological, and metabolic disorders, among other developmental and chronic impairments. One of the objectives of the H2020 European Human Biomonitoring Initiative (HBM4EU) was the development of informative effect biomarkers for application in a more systematic and harmonized way in large-scale European HBM studies. The inclusion of effect biomarkers would complement exposure data with mechanistically-based information on early and late adverse effects. For this purpose, a stepwise strategy was developed to identify and implement a panel of validated effect biomarkers in European HBM studies. This work offers an overview of the complete procedure followed, from comprehensive literature search strategies, selection of criteria for effect biomarkers and their classification and prioritization, based on toxicological data and adverse outcomes, to pilot studies for their analytical, physiological, and epidemiological validation. We present the example of one study that demonstrated the mediating role of the effect biomarker status of brain-derived neurotrophic factor BDNF in the longitudinal association between infant bisphenol A (BPA) exposure and behavioral function in adolescence. A panel of effect biomarkers has been implemented in the HBM4EU Aligned Studies as main outcomes, including traditional oxidative stress, reproductive, and thyroid hormone biomarkers. Novel biomarkers of effect, such as DNA methylation status of BDNF and kisspeptin (KISS) genes were also evaluated as molecular markers of neurological and reproductive health, respectively. A panel of effect biomarkers has also been applied in HBM4EU occupational studies, such as micronucleus analysis in lymphocytes and reticulocytes, whole blood comet assay, and malondialdehyde, 8-oxo-2'-deoxyguanosine and untargeted metabolomic profile in urine, to investigate, for example, biological changes in response to hexavalent chromium Cr(VI) exposure. The use of effect biomarkers in HBM4EU has demonstrated their ability to detect early biological effects of chemical exposure and to identify subgroups that are at higher risk. The roadmap developed in HBM4EU confirms the utility of effect biomarkers, and support one of the main objectives of HBM research, which is to link exposure biomarkers to mechanistically validated effect and susceptibility biomarkers in order to better understand the public health implications of human exposure to environmental chemicals.PMID:36841007 | DOI:10.1016/j.ijheh.2023.114140

Nanoplastics induce more severe multigenerational life-history trait changes and metabolic responses in marine rotifer Brachionus plicatilis: Comparison with microplastics

Sat, 25/02/2023 - 12:00
J Hazard Mater. 2023 Feb 23;449:131070. doi: 10.1016/j.jhazmat.2023.131070. Online ahead of print.ABSTRACTMicro/nanoplastics (MPs/NPs) have attracted global attention for their potential adverse impacts on marine ecosystems. This study investigated the impacts of MPs/NPs (70 nm, 500 nm, and 2 µm) on population growth and life-history traits of marine rotifer (Brachionus plicatilis), and further explored the differences from the aspects of nutrient accumulation and metabolomic profiles. The results showed that 200 and 2000 µg/L 70 nm NPs significantly suppressed population growth, and negatively affected life span, the first spawning and breeding time, and fecundity in F0-F2 generation rotifers. Whereas 500 nm NPs and 2 µm MPs showed no effect on population growth 200 µg/L and only changed the life-history traits at the highest concentration. Moreover, 70 nm NPs were more easily accumulated in the rotifers and reduced food ingestion and nutrient accumulation, which caused more severe disruption on purine-pyrimidine metabolism, tricarboxylic acid cycle, and protein synthesis pathway compared to 500 nm NPs. Thus, the smaller the size of the plastic particles, the stronger the toxicity to the rotifers. This study provided new insights into the toxicity of MPs/NPs on marine zooplankton and proposed that metabolomics was powerful to explore the toxicity mechanisms of MPs/NPs.PMID:36840989 | DOI:10.1016/j.jhazmat.2023.131070

Effect of Enrofloxacin on the Microbiome, Metabolome, and Abundance of Antibiotic Resistance Genes in the Chicken Cecum

Sat, 25/02/2023 - 12:00
Microbiol Spectr. 2023 Feb 22:e0479522. doi: 10.1128/spectrum.04795-22. Online ahead of print.ABSTRACTEnrofloxacin is an important antibiotic for the treatment of Salmonella infections in livestock and poultry. However, the effects of different concentrations of enrofloxacin on the bacterial and metabolite compositions of the chicken gut and changes in the abundance of resistance genes in cecum contents remain unclear. To investigate the effects of enrofloxacin on chickens, we orally administered different concentrations of enrofloxacin to 1-day-old chickens and performed 16S rRNA gene sequencing to assess changes in the gut microbiomes of chickens after treatment. The abundance of fluoroquinolone (FQ) resistance genes was measured using quantitative PCR. Metabolomics techniques were used to examine the cecal metabolite composition. We found that different concentrations of enrofloxacin had different effects on cecum microorganisms, with the greatest effect on cecum microbial diversity in the low-concentration enrofloxacin group at day 7. Enrofloxacin use reduced the abundance of beneficial bacteria such as Lactobacillaceae and Oscillospira. Furthermore, cecum microbial diversity was gradually restored as the chickens grew. In addition, enrofloxacin increased the abundance of resistance genes, and there were differences in the changes in abundance among different antibiotic resistance genes. Moreover, enrofloxacin significantly affected linoleic acid metabolism, amino acid metabolism, and signaling pathways. This study helps improve our understanding of how antibiotics affect host physiological activities and provides new insights into the rational use of drugs in poultry farming. The probiotics and metabolites that we identified could be used to modulate the negative effects of antibiotics on the host, which requires further study. IMPORTANCE In this study, we investigated changes in the cecum flora, metabolites, and abundances of fluoroquinolone antibiotic resistance genes in chickens following the use of different concentrations of enrofloxacin. These results were used to determine the effects of enrofloxacin on chick physiology and the important flora and metabolites that might contribute to these effects. In addition, these results could help in assessing the effect of enrofloxacin concentrations on host metabolism. Our findings could help guide the rational use of antibiotics and mitigate the negative effects of antibiotics on the host.PMID:36840593 | DOI:10.1128/spectrum.04795-22

Capacity of a Microbial Synbiotic To Rescue the <em>In Vitro</em> Metabolic Activity of the Gut Microbiome following Perturbation with Alcohol or Antibiotics

Sat, 25/02/2023 - 12:00
Appl Environ Microbiol. 2023 Feb 22:e0188022. doi: 10.1128/aem.01880-22. Online ahead of print.ABSTRACTThe human gut microbiome contributes crucial bioactive metabolites that support human health and is sensitive to perturbations from the ingestion of alcohol and antibiotics. We interrogated the response and recovery of human gut microbes after acute alcohol or broad-spectrum antibiotic administration in a gut model simulating the luminal and mucosal colonic environment with an inoculated human microbiome. Both alcohol and antibiotic treatments reduced the production of major short-chain fatty acids (SCFAs) (acetate, propionate, and butyrate), which are established modulators of human health. Treatment with a microbial synbiotic restored and enhanced gut function. Butyrate and acetate production increased by up to 29.7% and 18.6%, respectively, relative to untreated, dysbiotic samples. In parallel, treatment led to increases in the relative abundances of beneficial commensal organisms not found in the synbiotic (e.g., Faecalibacterium prausnitzii and the urolithin-producing organism Gordonibacter pamelaeae) as well as species present in the synbiotic (e.g., Bifidobacterium infantis), suggesting synergistic interactions between supplemented and native microorganisms. These results lead us to conclude that functional shifts in the microbiome, evaluated by both metabolite production and specific taxonomic compositional changes, are an appropriate metric to assess microbiome "recovery" following a dysbiosis-inducing disruption. Overall, these findings support the execution of randomized clinical studies to determine whether a microbial synbiotic can help restore microbiome function after a disruption. IMPORTANCE The human gut microbiome is sensitive to disruptions by common stressors such as alcohol consumption and antibiotic treatment. In this study, we used an in vitro system modeling the gut microbiome to investigate whether treatment with a microbial synbiotic can help restore microbiome function after stress. We find that a complex gut community treated with alcohol or antibiotics showed reduced levels of production of short-chain fatty acids, which are critical beneficial molecules produced by a healthy gut microbiota. Treatment of stressed communities with a microbial synbiotic resulted in the recovery of SCFA production as well as an increase in the abundance of beneficial commensal organisms. Our results suggest that treatment with a microbial synbiotic has the potential to restore healthy gut microbiome function after stress and merits further investigation in clinical studies.PMID:36840551 | DOI:10.1128/aem.01880-22

Age- and body composition-dependent association of child gut microbial enterotype with puberty timing: a Chinese cohort

Sat, 25/02/2023 - 12:00
J Clin Endocrinol Metab. 2023 Feb 24:dgad090. doi: 10.1210/clinem/dgad090. Online ahead of print.ABSTRACTCONTEXT: Puberty timing, which is vital for adult well-being, has been suggested to be linked to specific gut taxa recently. However, the impact of comprehensive gut microbiome structure assessed by enterotype on puberty timing remains unknown.OBJECTIVE: Investigate the prospective association of gut microbial enterotype with puberty timing and the potential interaction of age and body composition.METHODS: This study included 1826 children from the Chinese Adolescent Cohort Study, a cohort that collects information on sociodemographics, dietary intake, physical activity, anthropometry, and pubertal development of children aged 6 to 8 since 2013 and follows up annually until their age of 15. Fecal samples were collected annually since 2019 and analyzed for 16S rRNA sequencing and targeted fecal metabolomics. Cox proportional hazard regression models were used to investigate the prospective association of enterotype with puberty timing and the impact of age and body mass index (BMI) sex- and age-independent standard deviation scores (SDS).RESULTS: 592 (32.4%) and 1234 (67.6%) children belonged to the Prevotella-rich enterotype and the Bacteroides-rich enterotype, respectively. Children with the Bacteroides-rich enterotype experienced their menarche/voice break later than those with the Prevotella-enterotype (hazard ratio 0.53 (95%CI, 0.28-0.98), P = 0.02). Moreover, this association was more pronounced among younger children with higher BMI SDS (P for-interaction = 0.006).CONCLUSION: Our findings supported a role for gut microbial communities in pubertal development, in which younger children with higher body mass seems more sensitive.PMID:36840481 | DOI:10.1210/clinem/dgad090

Defensive Resistance of Cowpea <em>Vigna unguiculata</em> Control <em>Megalurothrips usitatus</em> Mediated by Jasmonic Acid or Insect Damage

Sat, 25/02/2023 - 12:00
Plants (Basel). 2023 Feb 19;12(4):942. doi: 10.3390/plants12040942.ABSTRACTVigna unguiculata is a vital vegetable crop in Southeast Asia, and Megalurothrips usitatus can cause huge damage to this crop. Enhancing the resistance of V. unguiculata against M. usitatus is a promising way to protect this crop; however, there is limited information regarding the mechanism underlying the resistance of V. unguiculata against M. usitatus. Here, a behavior assay was performed to explore the resistance of V. unguiculata against M. usitatus after insect damage or treatment by jasmonic acid (JA). Furthermore, transcriptome and metabonomics analysis was used to detect the putative mechanism underlying the resistance of V. unguiculata against M. usitatus. The pre-treatment of Vigna unguiculata with JA or infestation with Megalurothrips usitatus alleviated the damage resulting from the pest insect. We further identified differentially expressed genes and different metabolites involved in flavonoid biosynthesis and alpha-linolenic acid metabolism. Genes of chalcone reductase and shikimate O-hydroxycinnamoyltransferase involved in flavonoid biosynthesis, as well as lipoxygenase and acyl-CoA oxidase involved in alpha-linolenic acid metabolism, were upregulated in plants after herbivory or JA supplementation. The upregulation of these genes contributed to the high accumulation of metabolites involved in flavonoid biosynthesis and the alpha-linolenic acid metabolism pathway. These transcriptional and metabolite changes are potentially responsible for plant defense and a putative regulatory model is thus proposed to illustrate the cowpea defense mechanism against insect attack. Our study provides candidate targets for the breeding of varieties with resistance to insect herbivory by molecular technology.PMID:36840292 | DOI:10.3390/plants12040942

Metabolic Profiling Identifies Changes in the Winter Wheat Grains Following <em>Fusarium</em> Treatment at Two Locations in Croatia

Sat, 25/02/2023 - 12:00
Plants (Basel). 2023 Feb 17;12(4):911. doi: 10.3390/plants12040911.ABSTRACTFusarium head blight (FHB) is one of the most dangerous diseases of winter wheat, resulting in reduced grain yield and quality, and production of mycotoxins by the Fusarium fungi. In the present study, changes in the grain metabolomics of winter wheat samples infected with Fusarium spp. and corresponding non-infected samples from two locations in Croatia were investigated by GC-MS. A Mann-Whitney test revealed that 24 metabolites detected were significantly separated between Fusarium-inoculated and non-infected samples during the variety by treatment interactions. The results confirmed that in grains of six FHB-resistant varieties, ten metabolites were identified as possible resistance-related metabolites. These metabolites included heptadecanoic acid, 9-(Z)-hexadecenoic acid, sophorose, and secolaganin in grains of FHB-resistant varieties at the Osijek location, as well as 2-methylaminomethyltartronic acid, maleamic acid, 4-hydroxyphenylacetonitrile, 1,4-lactonearabinonic acid, secolaganin, and alanine in grains of FHB-resistant varieties at the Tovarnik location. Moreover, on the PCA bi-plot, FHB-susceptible wheat varieties were closer to glycyl proline, decanoic acid, and lactic acid dimer that could have affected other metabolites, and thus, suppressed resistance to FHB. Although defense reactions were genetically conditioned and variety specific, resulting metabolomics changes may give insight into defense-related pathways that could be manipulated to engineer plants with improved resistance to the pathogen.PMID:36840259 | DOI:10.3390/plants12040911

Genetic and Metabolite Variability among Commercial Varieties and Advanced Lines of <em>Vicia faba</em> L

Sat, 25/02/2023 - 12:00
Plants (Basel). 2023 Feb 17;12(4):908. doi: 10.3390/plants12040908.ABSTRACTVicia faba L. (faba bean) is one of the most promising pulse crops due to its nutritional value and high nitrogen fixation capacity. The aim of the present study was to compare the genetic diversity and the seed metabolite profiles of five genetic materials of faba bean. Specifically, three newly developed advanced lines (KK18, KK14 and KK10) and two commercial cultivars (POLIKARPI and TANAGRA), were evaluated for this purpose. Genetic diversity among populations was assessed by SCoT molecular markers. Through UPGMA dendrogram, genetic distances between populations were estimated. Untargeted metabolomics analysis of the seeds was performed employing GC/EI/MS. The cultivar POLYKARPI exhibited the highest polymorphism. All varieties showed a higher within-cultivars and advanced lines variability than between. POLYKARPI and KK14 had the lowest genetic distances, while KK18 and TANAGRA presented the highest ones. The advanced line KK18 displayed the best nutritional profile, the highest concentration of desirable metabolites (lactic acid and trehalose), the lowest concentration of anti-nutritional factors (oxalic acid) and the lowest concentration of saturated fatty acids (palmitic and stearic acid). According to the results of the present study, KK18 line is a very promising material for further exploration and utilization in breeding programs.PMID:36840256 | DOI:10.3390/plants12040908

Untargeted Metabolomics for Integrative Taxonomy: Metabolomics, DNA Marker-Based Sequencing, and Phenotype Bioimaging

Sat, 25/02/2023 - 12:00
Plants (Basel). 2023 Feb 15;12(4):881. doi: 10.3390/plants12040881.ABSTRACTIntegrative taxonomy is a fundamental part of biodiversity and combines traditional morphology with additional methods such as DNA sequencing or biochemistry. Here, we aim to establish untargeted metabolomics for use in chemotaxonomy. We used three thallose liverwort species Riccia glauca, R. sorocarpa, and R. warnstorfii (order Marchantiales, Ricciaceae) with Lunularia cruciata (order Marchantiales, Lunulariacea) as an outgroup. Liquid chromatography high-resolution mass-spectrometry (UPLC/ESI-QTOF-MS) with data-dependent acquisition (DDA-MS) were integrated with DNA marker-based sequencing of the trnL-trnF region and high-resolution bioimaging. Our untargeted chemotaxonomy methodology enables us to distinguish taxa based on chemophenetic markers at different levels of complexity: (1) molecules, (2) compound classes, (3) compound superclasses, and (4) molecular descriptors. For the investigated Riccia species, we identified 71 chemophenetic markers at the molecular level, a characteristic composition in 21 compound classes, and 21 molecular descriptors largely indicating electron state, presence of chemical motifs, and hydrogen bonds. Our untargeted approach revealed many chemophenetic markers at different complexity levels that can provide more mechanistic insight into phylogenetic delimitation of species within a clade than genetic-based methods coupled with traditional morphology-based information. However, analytical and bioinformatics analysis methods still need to be better integrated to link the chemophenetic information at multiple scales.PMID:36840229 | DOI:10.3390/plants12040881

Nutritional Composition and Antioxidant Activity of <em>Gonostegia hirta</em>: An Underexploited, Potentially Edible, Wild Plant

Sat, 25/02/2023 - 12:00
Plants (Basel). 2023 Feb 15;12(4):875. doi: 10.3390/plants12040875.ABSTRACTWild, edible plants have received increasing attention as an important complement to cultivate vegetables, as they represent an easily accessible source of nutrients, mineral elements, and antioxidants. In this study, the tender stems and leaves of Gonostegia hirta, an edible species for which only scarce data are available in the literature, are thoroughly evaluated for their nutritional profile, chemical characterization, and antioxidant activity. Being considered as an underexploited, potentially edible plant, the nutritional composition of Gonostegia hirta was identified, and several beneficial compounds were highlighted: sugars, potassium, calcium, organic acids, fatty acids, phenolics, and flavonoids. A total of 418 compounds were identified by metabolomic analysis, including phenolic acids, flavonoids, amino acids, lipids, organic acids, terpenoids, alkaloids, nucleotides, tannins, lignans, and coumarin. The plant sample was found to have good antioxidant capacities, presented by DPPH, FRAP, ABTS+, hydroxyl radical scavenging capacity, and its resistance to the superoxide anion radical test. In general, Gonostegia hirta has a good nutritional and phytochemical composition. The health benefits of Gonostegia hirta as a vegetable and herbal medicine is important for both a modern diet and use in medication.PMID:36840225 | DOI:10.3390/plants12040875

Cytogenetic Characterization and Metabolomic Differences of Full-Sib Progenies of <em>Saccharum</em> spp

Sat, 25/02/2023 - 12:00
Plants (Basel). 2023 Feb 10;12(4):810. doi: 10.3390/plants12040810.ABSTRACTSugarcane smut is a worldwide fungal disease. Disease resistance breeding is the most economical and effective measure to prevent and control sugarcane smut. The cytogenetic characteristics and metabolomic differences of sugarcane F1s are closely related to disease resistance. Zhongzhe 1 and G160 sugarcane from the same parents (ROC25 and Yunzhe89-7) were used; the plants were grown in accordance with the barrel method. When the seedlings had 4-5 leaves, genomic in situ hybridization (GISH) was performed; digoxigenin (DIG)-labeled female parental (ROC25)DNA and biotin-labeled male parental (Yunzhe89-7) DNA were used as probes, and the karyotypes of two hybrids were analyzed. The new sugarcane smut-resistant variety (Zhongzhe 1) and the susceptible variety (G160) derived from the same parent were analyzed via gas chromatography-mass spectrometry technology (GC-MS) to compare the metabolomic differences between them. GISH analysis revealed that the chromosome ploidy number of Zhongzhe 1 sugarcane and G160 sugarcane were 114 and 110, respectively. However, the two contain different numbers of chromosomes from the female (ROC25) and male (Yunzhe89-7) parents. Moreover, 258 significantly changed metabolites were identified in smut-resistant Zhongzhe 1, as compared with the smut-susceptible G160 sugarcane: 56 flavonoids, 52 phenolic acids, 30 lipids, 26 organic acids, 26 amino acids and derivatives, 19 nucleotides and derivatives, 5 alkaloids, 9 terpenoids, and 35 others. Multivariate statistical analysis revealed a distinct difference in metabolic pathways between Zhongzhe 1 sugarcane and G160, and both of these varieties had unique functional metabolites. Differences in chromosome composition may constitute the genetic basis for the difference in resistance to smut disease between Zhongzhe 1 sugarcane and G160 sugarcane, and a high accumulation of flavonoids, lipids, terpenoids and tannins may constitute the basis of resistance to smut disease for the Zhongzhe 1 variety.PMID:36840158 | DOI:10.3390/plants12040810

Metabolomic Analysis Reveals the Metabolic Diversity of Wild and Cultivated Stellaria Radix (<em>Stellaria dichotoma</em> L. var. <em>lanceolata</em> Bge.)

Sat, 25/02/2023 - 12:00
Plants (Basel). 2023 Feb 9;12(4):775. doi: 10.3390/plants12040775.ABSTRACTStellaria Radix, called Yinchaihu in Chinese, is a traditional Chinese medicine, which is obtained from the dried roots of Stellaria dichotoma L. var. lanceolata Bge. Cultivated yinchaihu (YCH) has become a main source of production to alleviate the shortage of wild plant resources, but it is not clear whether the metabolites of YCH change with the mode of production. In this study, the contents of methanol extracts, total sterols and total flavonoids in wild and cultivated YCH are compared. The metabolites were analyzed by ultra-high performance liquid chromatography-tandem time-of-flight mass spectrometry. The content of methanol extracts of the wild and cultivated YCH all exceeded the standard content of the Chinese Pharmacopoeia. However, the contents of total sterols and total flavonoids in the wild YCH were significantly higher than those in the cultivated YCH. In total, 1586 metabolites were identified by mass spectrometry, and 97 were significantly different between the wild and cultivated sources, including β-sitosterol, quercetin derivatives as well as many newly discovered potential active components, such as trigonelline, arctiin and loganic acid. The results confirm that there is a rich diversity of metabolites in the wild and cultivated YCH, and provide a useful theoretical guidance for the evaluation of quality in the production of YCH.PMID:36840123 | DOI:10.3390/plants12040775

Metabolite Profiling Reveals the Effect of Cold Storage on Primary Metabolism in Nectarine Varieties with Contrasting Mealiness

Sat, 25/02/2023 - 12:00
Plants (Basel). 2023 Feb 8;12(4):766. doi: 10.3390/plants12040766.ABSTRACTChilling injury is a physiological disorder caused by cold storage in peaches and nectarines. The main symptom of chilling injury is mealiness/wooliness, described as a lack of juice in fruit flesh. In this work, we studied two nectarine varieties (Andes Nec-2 and Andes Nec-3) with contrasting susceptibility to mealiness after cold storage. A non-targeted metabolomic analysis was conducted by GC-MS to understand if changes in metabolite abundance are associated with nectarine mealiness induced by cold storage. Multivariate analyses indicated that in unripe nectarines, cold storage promoted a higher accumulation of amino acids in both varieties. Interestingly, for ripe nectarines, cold storage induced an accumulation of fewer amino acids in both varieties and showed an increased abundance of sugars and organic acids. A pathway reconstruction of primary metabolism revealed that in ripe nectarines, cold storage disrupted metabolite abundance in sugar metabolism and the TCA cycle, leading to a differential accumulation of amino acids, organic acids, and sugars in mealy and juicy nectarines.PMID:36840114 | DOI:10.3390/plants12040766

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