PubMed

Am J Mens Health. 2023 Jan-Feb;17(1):15579883231153018. doi: 10.1177/15579883231153018.ABSTRACTBirthplace, as a proxy for environmental exposures (e.g., diet), may influence metabolomic profiles and influence risk of cancer. This secondary analysis investigated metabolomic profile differences between foreign and U.S.-born Mexican-origin (MO) Hispanic men to shed light on potential mechanisms through which foreign- and U.S.-born individuals experience differences in cancer risk and risk factors. Plasma samples from MO Hispanic men (N = 42) who participated in a previous lifestyle intervention were collected pre-and post-intervention. Metabolomic profiles were characterized from samples using ultra performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-QTOF). Models were visualized using supervised orthogonal projections to latent structures-discriminant analysis (OPLS-DA). Progenesis QI was used for peak integration and metabolite identification. Plasma metabolomic profiles differed between foreign- and U.S.-born pre-intervention (R2 = .65) and post-intervention (R2 = .62). Metabolomic profiles differed pre- versus post-intervention (R2 = .35 and R2 = .65) for the foreign- and U.S.-born group, respectively. Both endogenous metabolites and dietary components characterized differences between foreign- and U.S.-born participants pre- and post-intervention. Plasma metabolomic profiles from MO Hispanic men differed by birthplace. These results advance our understanding of relevant exposures that may affect cancer risk among MO Hispanic men born abroad or in the United States.PMID:36842961 | DOI:10.1177/15579883231153018

J Ethnopharmacol. 2023 Feb 24:116301. doi: 10.1016/j.jep.2023.116301. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Yiyi Fuzi Baijiang formula (YFB) is a traditional Chinese medicine prescription composed of Coix seed, Radix Aconiti Lateralis and Patrinia villosa, which has been used to treat ulcerative colitis (UC) for thousands of years.AIM OF THE STUDY: To investigate the therapeutic effect and metabolic analysis of YFB formula on UC in rats induced by 2,4,6-trinitro-benzene sulfonic acid (TNBS).MATERIALS AND METHODS: Six main alkaloids in the YFB formula were determined by UPLC‒MS/MS. The rat UC model was induced by TNBS, and the therapeutic effect of YFB formula on UC was evaluated by disease activity index (DAI) score and hematoxylin-eosin (HE) staining. UPLC-QTRAP-MS metabolomics technology was used to screen potential biomarkers for YFB treatment of UC in combination with multivariate data statistics and further analyze related metabolic pathways. Western blotting was used to detect the protein levels of NLRP1, NLRP3, NLRC4, ASC, pro-caspase1 and Caspase-1 in rat liver tissues. ELISA and immunohistochemistry were used to detect the contents of interleukin (IL)-17A, IL-21, IL-22, IL-6, TNF-α, IL-1β and IL-18 in rat serum and liver tissues.RESULTS: The DAI scores of the YFB groups were significantly reduced, and colon tissue injury was significantly improved (p < 0.01). The results of metabolomics analysis revealed 29 potential biomarkers in serum and 27 potential biomarkers in liver. YFB formula can treat UC by affecting glycerophospholipid metabolism, primary bile acid biosynthesis, glyoxylic acid and dicarboxylic acid metabolism, and arginine and proline metabolism. Compared with the model group, the contents of IL-17A, IL-21, IL-22, IL-6, TNF-α, IL-1β and IL-18 in the YFB groups were decreased in a dose-dependent manner (p < 0.01). Compared with those in the model group, the protein levels of NLRP1, NLRP3, NLRC4, ASC, pro-caspase1 and Caspase-1 in the YFB groups were significantly decreased in a dose-dependent manner (p < 0.01).CONCLUSIONS: The therapeutic effect of YFB formula on UC rats was dose dependent, and the effect of the YFB (2.046 g/kg) group was close to that of the positive group. YFB formula has an anti-inflammatory effect on UC by regulating the balance of Th17/Treg cells in rats.PMID:36842724 | DOI:10.1016/j.jep.2023.116301

Gastroenterology. 2023 Feb 24:S0016-5085(23)00164-6. doi: 10.1053/j.gastro.2023.02.025. Online ahead of print.ABSTRACTBACKGROUND & AIMS: Although small patient subsets benefit from current targeted strategies or immunotherapy, gemcitabine remains the first-line drug for pancreatic cancer (PC) treatment. However, gemcitabine resistance is widespread and compromises long-term survival. Here, we identified ubiquitin-conjugating enzyme E2T (UBE2T) as a potential therapeutic target to combat gemcitabine resistance in PC.METHODS: Proteomics and metabolomics were combined to examine the effect of UBE2T on pyrimidine metabolism remodeling. Spontaneous PC mice (LSL-KrasG12D/+, LSL-Trp53R172H/+, Pdx1-Cre; KPC) with Ube2t-conditional knockout, organoids, and large-scale clinical samples were used to determine the effect of UBE2T on gemcitabine efficacy. Organoids, patient-derived xenografts (PDX), and KPC mice were used to examine the efficacy of the combination of a UBE2T inhibitor and gemcitabine.RESULTS: Spontaneous PC mice with Ube2t deletion had a marked survival advantage following gemcitabine treatment, and UBE2T levels were positively correlated with gemcitabine resistance in clinical patients. Mechanistically, UBE2T catalyzes RING1-mediated ubiquitination of p53 and relieves the transcriptional repression of RRM1 and RRM2, resulting in unrestrained pyrimidine biosynthesis and alleviation of replication stress. Additionally, high-throughput compound library screening using organoids identified pentagalloylglucose (PGG) as a potent UBE2T inhibitor and gemcitabine sensitizer. The combination of gemcitabine and PGG diminished tumor growth in PDX models and prolonged long-term survival in spontaneous PC mice.CONCLUSIONS: Collectively, UBE2T-mediated p53 degradation confers PC gemcitabine resistance by promoting pyrimidine biosynthesis and alleviating replication stress. This study offers an opportunity to improve PC survival by targeting UBE2T and develop a promising gemcitabine sensitizer in clinical translation setting.PMID:36842710 | DOI:10.1053/j.gastro.2023.02.025

J Magn Reson. 2023 Feb 21;349:107405. doi: 10.1016/j.jmr.2023.107405. Online ahead of print.ABSTRACTIn this work we demonstrate the use of microfluidic NMR for in situ culture and quantitative analysis of metabolism in hepatocellular carcinoma (HCC) cell lines. A hydrothermal heating system is used to enable continuous in situ NMR observation of HCC cell culture over a 24 h incubation period. This technique is nondestructive, non-invasive and can measure millimolar concentrations at microlitre volumes, within a few minutes and in precisely controlled culture conditions. This is sufficient to observe changes in primary energy metabolism, using around 500-3500 cells per device, and with a time resolution of 17 min. The ability to observe intracellular responses in a time-resolved manner provides a more detailed view of a biological system and how it reacts to stimuli. This capability will allow detailed metabolomic studies of cell-culture based cancer models, enabling quantification of metabolic reporgramming, the metabolic tumor microenvironment, and the metabolic interplay between cancer- and immune cells.PMID:36842430 | DOI:10.1016/j.jmr.2023.107405

Environ Int. 2023 Feb 13;173:107819. doi: 10.1016/j.envint.2023.107819. Online ahead of print.ABSTRACTAgriculture-related manufactured nano-objects (MNOs) can revolutionize the crop production and help to achieve sustainable development goals. MNOs with diverse physico-chemical properties and ability to encapsulate and deliver active ingredients in controlled, targeted and stimuli responsive manner can enhance the efficiency while minimizing collateral damage to non-target organisms and environment. Application of MNOs in the form of nanopesticides and nanofertilizers is known to affect soil microbial communities both positively and negatively, but detailed studies with varying dose, type and environmental conditions are scarce. Therefore, it is imperative to understand the complex mechanisms and factors which shape the MNOs-microbial interactions through integrating state of the art technologies including omics (transcriptomics, metabolomics, and proteomics), artificial intelligence, and statistical frameworks. Lastly, we propose the idea of MNOs-mediated manipulation of soil microbiome to modify the soil microbial communities for improved microbial services. These microbial services, if harnessed appropriately, can revolutionize modern agriculture and help in achieving sustainable development goals.PMID:36842382 | DOI:10.1016/j.envint.2023.107819

J Pharm Biomed Anal. 2023 Feb 13;228:115295. doi: 10.1016/j.jpba.2023.115295. Online ahead of print.ABSTRACTAconiti Lateralis Radix Praeparata is one of the most famous traditional Chinese medicines possessing a variety of pharmacological activities on top of the toxicities. Due to the heterogeneity and non-standardization of the processing procedures, the subtypes and contents of the differential compounds between different processed products still remained indistinct, causing great risk in their proper use. In order to achieve the comparison and quality evaluation of different processed products of Aconiti Lateralis Radix Praeparata and develop new processed products with less toxicity, a quantification and pseudotargeted metabolomics method was developed based on the dynamic MRM mode of triple quadrupole (QqQ) mass spectrometry, and multivariate statistical analysis methods were applied to compare different processed products. Method validation results indicated good specificity, linearity, repeatability, precision, stability and recovery of the established quantification method and good linearity, precision and stability of the pseudotargeted metabolomics method. Differential compounds of different processed products were screened out and further confirmed by the quantification results. At last, the processing procedures were optimized to obtain new processed products of "Heishunpian" (black slices) with less toxicity, in which the contents of the toxic diester-type diterpenoid alkaloids were reduced from 106.98 μg/g to 0.85-12.96 μg/g. This study provided a valuable reference for the establishment of comprehensive quality evaluation methods of herbal medicines and a scientific basis for the optimization of processing procedures of Aconiti Lateralis Radix Praeparata.PMID:36842334 | DOI:10.1016/j.jpba.2023.115295

Ultrason Sonochem. 2023 Feb 21;94:106339. doi: 10.1016/j.ultsonch.2023.106339. Online ahead of print.ABSTRACTThe current work combines headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC/MS) with multivariate analysis fusion metabonomics for examining metabolite profile changes. The correlation with metabolic pathways during the fermentation of kombucha tea were comprehensively explored. For optimizing the fermentation process, ultrasound-assisted factors were explored. A total of 132 metabolites released by fermented kombucha were detected by HS-SPME-GC/MS. We employed the principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) to present the relationship between aroma components and fermentation time, of which the first two principal components respectively accounted for 60.3% and 6.5% of the total variance. Multivariate statistical analysis showed that during the fermentation of kombucha tea, there were significant differences in the phenotypes of metabolites in the samples, and 25 characteristic metabolites were selected as biomarkers. Leaf alcohol was first proposed as the characteristic volatile in the fermentation process of kombucha. Furthermore, we addressed the generation pathways of characteristic volatiles, their formation mechanisms, and the transformational correlation among them. Our findings provide a roadmap for future kombucha fermentation processing to enhance kombucha flavor and aroma.PMID:36842214 | DOI:10.1016/j.ultsonch.2023.106339

Andrology. 2023 Feb 26. doi: 10.1111/andr.13412. Online ahead of print.ABSTRACTBACKGROUND: Asthenozoospermia is one of the essential causes of male infertility, and its incidence is significantly higher in obese men. Due to its complex etiology and unknown pathomechanism, the diagnosis and treatment of obesity-induced asthenozoospermia is a prevalent problem in reproductive medicine.OBJECTIVE: To explore major differential metabolites and metabolic pathways in seminal plasma and pathological mechanisms for obesity-induced asthenozoospermia.MATERIALS AND METHODS: We performed nontarget metabolomic studies on the seminal plasma of healthy with normal semen parameters men (HN group, n = 20), obese with normal semen parameters men (ON group, n = 20) and obesity-induced asthenozoospermia men (OA group, n = 20) based on gas chromatography-mass spectrometry (GC-MS). Metabolic profilings and related pathway analyses were conducted to discriminate differential metabolites and metabolic pathways.RESULTS: A total of 20 differential metabolites including fructose, succinic acid, aconitic acid, methylmaleic acid, glucopyranose, serine, valine, leucine, phenylalanine, glycine, glutamic acid, alanine, proline and threonine were identified in HN group and ON group, 24 differential metabolites including glucose, fructose, pyruvic acid, citric acid, succinic acid, aconitic acid, glucopyranose, glutamic acid, valine, leucine, glycine, phenylalanine, lysine, citrulline, proline and alanine were produced in OA group and ON group, and 28 differential metabolites including glucose, fructose, citric acid, succinic acid, glucopyranose, valine, glycine, serine, leucine, phenylalanine, alanine, threonine, proline, glutamic acid, citrulline, lysine and tyrosine were produced in OA group and HN group. In addition, abnormal energy metabolism including carbohydrate metabolism (TCA cycle, glycolysis/gluconeogenesis and pyruvate metabolism) and amino acid metabolism (phenylalanine, tyrosine and tryptophan biosynthesis, D-glutamine and D-glutamate metabolism; phenylalanine metabolism, etc.) were found in ON group and OA group.CONCLUSION: Obesity could affect the metabolite composition in seminal plasma and abnormal energy metabolism in seminal plasma mainly including carbohydrate metabolism and amino acid metabolism was closely related to obesity-induced asthenozoospermia. This article is protected by copyright. All rights reserved.PMID:36841993 | DOI:10.1111/andr.13412

J Sep Sci. 2023 Feb 26:e2201004. doi: 10.1002/jssc.202201004. Online ahead of print.ABSTRACTEpilepsy is a complex neurological disease characterized by spontaneous recurrent seizures that affects around 1% of the global population. Despite the significant progress in the mechanisms of epileptogenesis, there is still about 60% of cases in which the cause is unknown. Thus, revealing the molecular mechanisms of epileptogenesis will greatly improve the development of epilepsy treatment. Since comprehensive characterization of amino acids and water-soluble vitamins is important in understanding the underlying mechanisms of epilepsy or seizures, we developed two liquid chromatography-tandem mass spectrometry methods to quantify 17 water-soluble vitamins and 46 amino acids and applied them to our pentylenetetrazole-induced kindling rat model. All water-soluble vitamins were detected with a linearity of r > 0.992 and limits of quantitation between 0.1 and 5 ng/ml except for nicotinic acid. For amino acids, the linearities obtained were good with correlation coefficients higher than 0.99, and matrix effects were between 85.3 and 110%. To handle the multidimensional data more effectively, multivariate statistical analysis approaches used in non-targeted metabolomics were creatively exploited in the visualization, interpretation, and exploration of the results. This article is protected by copyright. All rights reserved.PMID:36841992 | DOI:10.1002/jssc.202201004

Eye (Lond). 2023 Feb 25. doi: 10.1038/s41433-023-02457-4. Online ahead of print.ABSTRACTBACKGROUND: Pathological myopia (PM) is closely associated with blinding ocular morbidities. Identifying biomarkers can provide clues on pathogeneses. This study aimed to identify metabolic biomarkers and underlying mechanisms in the vitreous humour (VH) of PM patients with complications.METHODS: VH samples were collected from 39 PM patients with rhegmatogenous retinal detachment (RRD) (n = 23) or macular hole (MH)/myopic retinoschisis (MRS) (n = 16) and 23 controls (MH with axial length < 26 mm) who underwent surgical treatment. VH metabolomic profiles were investigated using ultra-performance liquid chromatography‒mass spectrometry. The area under the receiver operating characteristic curve (AUC) was computed to identify potential biomarkers for PM diagnosis.RESULTS: Bioinformatics analysis identified nineteen and four metabolites altered in positive and negative modes, respectively, and these metabolites were involved in tryptophan metabolism. Receiver operating characteristic analysis showed that seventeen metabolites (AUC > 0.6) in the positive mode and uric acid in the negative mode represent potential biomarkers for PM with complications (AUC = 0.894). Pairwise and pathway analyses among the RRD-PM, MH/MRS-PM and control groups showed that tryptophan metabolism and uric acid were closely correlated with PM. Altered metabolites and pathways in our study were characterized by increased oxidative stress and altered energy metabolism. These results contribute to a better understanding of myopia progression with or without related complications.CONCLUSIONS: Our study provides metabolomic signatures and related immunopathological features in the VH of PM patients, revealing new insight into the prevention and treatment of PM and related complications.PMID:36841867 | DOI:10.1038/s41433-023-02457-4

Sci Rep. 2023 Feb 25;13(1):3296. doi: 10.1038/s41598-023-30231-9.ABSTRACTMetabolomics-derived metabolites (henceforth metabolites) may mediate the relationship between modifiable risk factors and clinical biomarkers of metabolic health (henceforth clinical biomarkers). We set out to study the associations of metabolites with clinical biomarkers and a potential mediation effect in a population of young adults. First, we conducted a systematic literature review searching for metabolites associated with 11 clinical biomarkers (inflammation markers, glucose, blood pressure or blood lipids). Second, we replicated the identified associations in a study population of n = 218 (88 males and 130 females, average age of 18 years) participants of the DONALD Study. Sex-stratified linear regression models adjusted for age and BMI and corrected for multiple testing were calculated. Third, we investigated our previously reported metabolites associated with anthropometric and dietary factors mediators in sex-stratified causal mediation analysis. For all steps, both urine and blood metabolites were considered. We found 41 metabolites in the literature associated with clinical biomarkers meeting our inclusion criteria. We were able to replicate an inverse association of betaine with CRP in women, between body mass index and C-reactive protein (CRP) and between body fat and leptin. There was no evidence of mediation by lifestyle-related metabolites after correction for multiple testing. We were only able to partially replicate previous findings in our age group and did not find evidence of mediation. The complex interactions between lifestyle factors, the metabolome, and clinical biomarkers warrant further investigation.PMID:36841863 | DOI:10.1038/s41598-023-30231-9

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

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

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

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

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

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

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

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

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