PubMed

EBioMedicine. 2022 Nov 10;86:104349. doi: 10.1016/j.ebiom.2022.104349. Online ahead of print.ABSTRACTBACKGROUND: The application of cold exposure has emerged as an approach to enhance whole-body lipid catabolism. The global effect of cold exposure on the lipidome in humans has been reported with mixed results depending on intensity and duration of cold.METHODS: This secondary study was based on data from a previous randomized cross-over trial (ClinicalTrials.gov ID: NCT03012113). We performed sequential lipidomic profiling in serum during 120 min cold exposure of human volunteers. Next, the intracellular lipolysis was blocked in mice (eighteen 10-week-old male wild-type mice C57BL/6J) using a small-molecule inhibitor of adipose triglyceride lipase (ATGL; Atglistatin), and mice were exposed to cold for a similar duration. The quantitative lipidomic profiling was assessed in-depth using the Lipidyzer platform.FINDINGS: In humans, cold exposure gradually increased circulating free fatty acids reaching a maximum at 60 min, and transiently decreased total triacylglycerols (TAGs) only at 30 min. A broad range of TAG species was initially decreased, in particular unsaturated and polyunsaturated TAG species with ≤5 double bonds, while after 120 min a significant increase was observed for polyunsaturated TAG species with ≥6 double bonds in humans. The mechanistic study in mice revealed that the cold-induced increase in polyunsaturated TAGs was largely prevented by blocking adipose triglyceride lipase.INTERPRETATION: We interpret these findings as that cold exposure feeds thermogenic tissues with TAG-derived fatty acids for combustion, resulting in a decrease of circulating TAG species, followed by increased hepatic production of polyunsaturated TAG species induced by liberation of free fatty acids stemming from adipose tissue.FUNDING: This work was supported by the Netherlands CardioVascular Research Initiative: 'the Dutch Heart Foundation, Dutch Federation of University Medical Centers, the Netherlands Organisation for Health Research and Development and the Royal Netherlands Academy of Sciences' [CVON2017-20 GENIUS-II] to Patrick C.N. Rensen. Borja Martinez-Tellez is supported by individual postdoctoral grant from the Fundación Alfonso Martin Escudero and by a Maria Zambrano fellowship by the Ministerio de Universidades y la Unión Europea - NextGenerationEU (RR_C_2021_04). Lucas Jurado-Fasoli was supported by an individual pre-doctoral grant from the Spanish Ministry of Education (FPU19/01609) and with an Albert Renold Travel Fellowship from the European Foundation for the Study of Diabetes (EFSD). Martin Giera was partially supported by NWO XOmics project #184.034.019.PMID:36371986 | DOI:10.1016/j.ebiom.2022.104349

J Chromatogr A. 2022 Nov 3;1685:463602. doi: 10.1016/j.chroma.2022.463602. Online ahead of print.ABSTRACTTryptophan, an essential amino acid, and its metabolites are involved in many physiological processes including neuronal functions, immune system, and gut homeostasis. Alterations to tryptophan metabolism are associated with various pathologies such as neurologic, psychiatric disorders, inflammatory bowel diseases (IBD), metabolic disorders, and cancer. It is consequently critical to develop a reliable, quantitative method for the analysis of tryptophan and its downstream metabolites from the kynurenine, serotonin, and indoles pathways. An LC-MS/MS method was designed for the analysis of tryptophan and 20 of its metabolites, without derivatization and performed in a single run. This method was validated for both serum and stool. The comparisons between serum and plasma, collected with several differing anticoagulants, showed significant differences only for serotonin. References values were established in sera and stools from healthy donors. For stool samples, as a proof of concept, the developed method was applied to a healthy control group and an IBD patient group. Results showed significant differences in the concentrations of tryptophan, xanthurenic acid, kynurenic acid, indole-3-lactic acid, and picolinic acid. This method allowed an extensive analysis of the three tryptophan metabolic pathways in two compartments. Beyond the application to IBD patients, the clinical use of this method is wide-ranging and may be applied to other pathological conditions involving tryptophan metabolism, such as neurological, psychiatric, or auto-inflammatory pathologies.PMID:36371922 | DOI:10.1016/j.chroma.2022.463602

Water Res. 2022 Nov 8;227:119339. doi: 10.1016/j.watres.2022.119339. Online ahead of print.ABSTRACTConstructed wetlands (CWs) are an important barrier to prevent nanoplastics (NPs) and microplastics (MPs) from entering receiving streams. However, little is known about how the accumulation of NPs affects the growth, photosynthesis, oxidative stress responses, and metabolism of plants, especially submerged plants that are widely used in CWs for water purification. Herein, we adopted Utricularia vulgaris (U. vulgaris), a typical submerged macrophyte as the model plant to address the above knowledge gaps under exposure to polystyrene NPs (PS-NPs, 500 nm, 0∼10 mg·L-1). Results showed that PS-NPs were absorbed by insect traps and further transported to stems and leaves of U. vulgaris, which limited plant height (6.8∼72.9%), relative growth rate (7.4∼17.2%), and photosynthesis (3.7∼28.2%). U. vulgaris suffered from oxidative stresses, as evidenced by the increase in malondialdehyde, antioxidant enzymes (catalase, peroxidase, and superoxide dismutase), and H2O2, especially under 1 and 10 mg·L-1. Abundances of 548 metabolites were quantified, and 291 metabolites were detected with altered levels after exposure, in which 25∼34% metabolites were up-regulated, and 32∼40% metabolites were down-regulated in metabolite expression. Metabolic pathways of the tricarboxylic acid cycle and amino acid were disrupted, in which citric acid, threonine, and adenine decreased, while amino acids (like serine, phenylalanine, histidine, etc.) increased first and then decreased with increasing PS-NPs concentrations. Moreover, PS-NPs reduced the removal efficiency of total nitrogen and phosphorus from water by U. vulgaris, bringing potential risks to aquatic ecosystems. These findings have greatly enhanced our understanding of the metabolic mechanisms and interactions of aquatic macrophytes that are heavily used in CWs in response to NPs stress, as well as the impact of NPs on CWs functioning.PMID:36371921 | DOI:10.1016/j.watres.2022.119339

Metabolomics. 2022 Nov 13;18(11):92. doi: 10.1007/s11306-022-01949-w.ABSTRACTINTRODUCTION: PKCδ is ubiquitously expressed in mammalian cells and its dysregulation plays a key role in the onset of several incurable diseases and metabolic disorders. However, much remains unknown about the metabolic pathways and disturbances induced by PKC deficiency, as well as the metabolic mechanisms involved.OBJECTIVES: This study aims to use metabolomics to further characterize the function of PKC from a metabolomics standpoint, by comparing the full serum metabolic profiles of PKC deficient mice to those of wild-type mice.METHODS: The serum metabolomes of PKCδ knock-out mice were compared to that of a wild-type strain using a GCxGC-TOFMS metabolomics research approach and various univariate and multivariate statistical analyses.RESULTS: Thirty-seven serum metabolite markers best describing the difference between PKCδ knock-out and wild-type mice were identified based on a PCA power value > 0.9, a t-test p-value < 0.05, or an effect size > 1. XERp prediction was also done to accurately select the metabolite markers within the 2 sample groups. Of the metabolite markers identified, 78.4% (29/37) were elevated and 48.65% of these markers were fatty acids (18/37). It is clear that a total loss of PKCδ functionality results in an inhibition of glycolysis, the TCA cycle, and steroid synthesis, accompanied by upregulation of the pentose phosphate pathway, fatty acids oxidation, cholesterol transport/storage, single carbon and sulphur-containing amino acid synthesis, branched-chain amino acids (BCAA), ketogenesis, and an increased cell signalling via N-acetylglucosamine.CONCLUSION: The charaterization of the dysregulated serum metabolites in this study, may represent an additional tool for the early detection and screening of PKCδ-deficiencies or abnormalities.PMID:36371785 | DOI:10.1007/s11306-022-01949-w

J Am Soc Mass Spectrom. 2022 Nov 13. doi: 10.1021/jasms.2c00082. Online ahead of print.ABSTRACTUltrahigh resolution mass spectrometry (UHR-MS) coupled with direct infusion (DI) electrospray ionization offers a fast solution for accurate untargeted profiling. Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers have been shown to produce a wealth of insights into complex chemical systems because they enable unambiguous molecular formula assignment even if the vast majority of signals is of unknown identity. Interlaboratory comparisons are required to apply this type of instrumentation in quality control (for food industry or pharmaceuticals), large-scale environmental studies, or clinical diagnostics. Extended comparisons employing different FT-ICR MS instruments with qualitative direct infusion analysis are scarce since the majority of detected compounds cannot be quantified. The extent to which observations can be reproduced by different laboratories remains unknown. We set up a preliminary study which encompassed a set of 17 laboratories around the globe, diverse in instrumental characteristics and applications, to analyze the same sets of extracts from commercially available standard human blood plasma and Standard Reference Material (SRM) for blood plasma (SRM1950), which were delivered at different dilutions or spiked with different concentrations of pesticides. The aim of this study was to assess the extent to which the outputs of differently tuned FT-ICR mass spectrometers, with different technical specifications, are comparable for setting the frames of a future DI-FT-ICR MS ring trial. We concluded that a cluster of five laboratories, with diverse instrumental characteristics, showed comparable and representative performance across all experiments, setting a reference to be used in a future ring trial on blood plasma.PMID:36371691 | DOI:10.1021/jasms.2c00082

Cell Biosci. 2022 Nov 12;12(1):183. doi: 10.1186/s13578-022-00919-y.ABSTRACTBACKGROUND: Exploiting cancer metabolism during nutrient availability holds immense potential for the clinical and therapeutic benefits of hepatocellular carcinoma (HCC) patients. Dietary methionine is a metabolic dependence of cancer development, but how the signal transduction integrates methionine status to achieve the physiological demand of cancer cells remains unknown.METHODS: Low or high levels of dietary methionine was fed to mouse models with patient-derived xenograft or diethyl-nitrosamine induced liver cancer. RNA sequence and metabolomics were performed to reveal the profound effect of methionine restriction on gene expression and metabolite changes. Immunostaining, sphere formation assays, in vivo tumourigenicity, migration and self-renewal ability were conducted to demonstrate the efficacy of methionine restriction and sorafenib.RESULTS: We discovered that mTORC1-c-Myc-SIRT4 axis was abnormally regulated in a methionine-dependent manner and affected the HCC progression. c-Myc rewires methionine metabolism through TRIM32 mediated degradation of SIRT4, which regulates MAT2A activity by ADP-ribosylation on amino acid residue glutamic acid 111. MAT2A is a key enzyme to generate S-adenosylmethionine (SAM). Loss of SIRT4 activates MAT2A, thereby increasing SAM level and dynamically regulating gene expression, which triggers the high proliferation rate of tumour cells. SIRT4 exerts its tumour suppressive function with targeted therapy (sorafenib) by affecting methionine, redox and nucleotide metabolism.CONCLUSIONS: These findings establish a novel characterization of the signaling transduction and the metabolic consequences of dietary methionine restriction in malignant liver tissue of mice. mTORC1, c-Myc, SIRT4 and ADP ribosylation site of MAT2A are promising clinical and therapeutic targets for the HCC treatment.PMID:36371321 | DOI:10.1186/s13578-022-00919-y

J Adv Res. 2022 Nov 9:S2090-1232(22)00251-X. doi: 10.1016/j.jare.2022.11.003. Online ahead of print.ABSTRACTINTRODUCTION: Currently, revealing how to prevent and control hyperuricemia has become an essential public health issue. Sulforaphane hasawiderangeofapplications in the management of hyperuricemia.OBJECTIVE: The study objective was to verify the uric acid-lowering effects and the regulation of the gut-kidney axis mediated by sulforaphane and identify host-microbial co-metabolites in hyperuricemia.METHODS: A hyperuricemia model was established by administering feedstuffs with 4% potassium oxonate and 20% yeast. Forty male Sprague-Dawley rats were randomly divided into the normal control, hyperuricemia, allopurinol, and sulforaphane groups. Animals were treated by oral gavage for six consecutive weeks, and then phenotypic parameters, metabolomic profiling, and metagenomicsequencing were performed.RESULTS: Sulforaphane could lower uric acid by decreasing urate synthesis and increasing renal urate excretion in hyperuricemic rats (P＜0.05). We identified succinic acid and oxoglutaric acid as critical host-gut microbiome co-metabolites. Moreover, sulforaphane improved the diversity of microbial ecosystems and functions, as well as metabolic control of the kidney. Notably, sulforaphane exerted its renoprotective effect through epigenetic modification of Nrf2 and interaction between gut microbiota and epigenetic modification in hyperuricemic rats.CONCLUSION: We revealed that sulforaphane could ameliorate the progression of hyperuricemia by reprogramming the gut microbiome and metabolome. Our findings may provide a good means for efficiently preventing and treating hyperuricemia.PMID:36371056 | DOI:10.1016/j.jare.2022.11.003

Environ Pollut. 2022 Nov 9:120635. doi: 10.1016/j.envpol.2022.120635. Online ahead of print.ABSTRACTDue to the wide application of plastic products in human life, microplastic pollution in water has recently attracted more attention. Many studies have revealed the size-dependent toxicity of microplastics. Here, we investigated the toxicological effects of polystyrene microplastics (PS-MPs) on the white leg shrimp, Litopenaeus vannamei, a profitable aquaculture species, using a comprehensive histomorphological, microbiome, and metabolomic approach to verify whether smaller particles are more toxic than larger particles. L. vannamei were experimentally exposed to water containing PS-MPs of four sizes (0.1, 1.0, 5.0, and 20.0 μm) for 24 h at 10 mg/L (acute experiment) and 12 d at 1 mg/L (subchronic experiment). After 24 h of acute exposure, PS-MP accumulation in shrimp indicated that the ingestion and egestion of PS-MPs had a size-dependent effect, and smaller particles were more bioavailable. The tissue morphological results of subchronic experiments showed that, for the guts and gills, the smaller sizes of the PS-MPs exhibited greater damage. In addition, 16 S rRNA gene amplicon sequencing showed that the alpha diversity was higher under larger PS-MP exposure. Correlated with changes in intestinal bacteria, we found a greater enrichment of metabolic pathways in hemolymph proteins and metabolites in larger PS-MP groups, such as "arginine and proline metabolism", "protein digestion and absorption", "lysine degradation". Interestingly, the activity or content of biomarkers of oxidative stress showed a peak at 1 μm and 5 μm. Under specific sizes of PS-MPs, the abundance of the pathogen Vibrio and probiotic bacteria Rhodobacter (5-μm) and Bacillus and Halomonas (1-μm) were simultaneously enriched. Our results indicated that PS-MP exposure can cause size-dependent damage to shrimp, yet specific particle size can be influential differently in regard to some research indicators. Therefore, it can enhance our comprehensive understanding of the impacts of microplastics on shrimp health and suggests that specific particle size should be considered when assessing the size-dependent toxicity of microplastics.PMID:36370970 | DOI:10.1016/j.envpol.2022.120635

Environ Pollut. 2022 Nov 9:120626. doi: 10.1016/j.envpol.2022.120626. Online ahead of print.ABSTRACTModern agriculture depends highly on pesticides and pharmaceutical preparations, so controlling exposure to these substances in the feed and food chain is essential. This article presents the first study on residues of a broad spectrum of pesticides and veterinary drugs in the diets of dairy cattle. One hundred and two representative samples of the complete diets, including basal feed rations and additional fed concentrate, were collected in three Austrian provinces (Styria, Lower and Upper Austria) in 2019 and 2020. The samples were tested for >700 pesticides, veterinary drugs and related metabolites using a validated method based on liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS). In total, 16 residues (13 pesticides and three veterinary drug residues) were detected. > 90% of the diets contained pesticide residues and <10% veterinary drug residues, whereas banned pesticides were not found. The most frequent pesticide residues were fluopyram (62%), piperonyl butoxide (39%) and diethyltoluamide (35%). The following pesticides exceed the default EU maximum residue level (MRL) (10 μg kg-1) for products exclusively used for animal feed production: Benzovindiflupyr (proportion of samples > MRLs: 1%), bixafen (2%), fluopyram (6%), ipconazole (1%) and tebuconazole (3%). Three residues (dinitrocarbanilide, monensin and nicarbazin) of veterinary drugs were identified, all below the MRLs. Over 60% of the evaluated samples contained mixtures of two to six residues/sample. Only one pesticide (diethyltoluamide) presented a significant difference among regions, with higher concentrations in Upper Austria. Brewery's spent grains were the dietary ingredient that showed the strongest correlation to pesticide residues. These findings evidence the realistic scenario of highly occurrent low doses of pesticides cocktails in the feed/food chain, which may affect the animal, human and environmental health. Since the risk assessments are based on single pesticides, the potential synergistic effect of co-occurring chemicals ("cocktail effect") requires further investigations.PMID:36370968 | DOI:10.1016/j.envpol.2022.120626

Free Radic Biol Med. 2022 Nov 9:S0891-5849(22)00969-8. doi: 10.1016/j.freeradbiomed.2022.11.007. Online ahead of print.ABSTRACTBACKGROUND: The joint influence of metabolic patterns on bone fragility has been rarely evaluated. We assessed the prospective association of plasma metabolic patterns with incident osteoporosis-related bone fractures in the Hortega Study participants. Redox balance plays a key role in bone metabolism. We also assessed differential associations in participant subgroups by redox-related metal exposure levels and candidate genetic variants.MATERIAL AND METHODS: In 467 participants older than 50 years from the Hortega Study, a representative sample from a region in Spain, we estimated metabolic principal components (mPC) for 54 plasma metabolites from NMR-spectrometry. BMD was calculated in the right calcaneus using Peripheral Instantaneous X-ray Imaging system. Metals biomarkers were measured in plasma by AAS and in urine by HPLC-ICPMS. Redox-related SNPs (N = 341) were measured by oligo-ligation assay.RESULTS: The prospective association with incident bone fractures was inverse for mPC1 (non-essential and essential amino acids, including branched-chain, and bacterial co-metabolites, including isobutyrate, trimethylamines and phenylpropionate, versus fatty acids and VLDL) and mPC4 (HDL), but positive for mPC2 (essential amino acids, including aromatic, and bacterial co-metabolites, including isopropanol and methanol). Participants with decreased selenium and increased antimony, arsenic and, suggestively, cadmium exposures showed higher mPC2-associated bone fractures risk. Genetic variants annotated to 19 genes, with the strongest evidence for NCF4, NOX4 and XDH, showed differential metabolic-related bone fractures risk.CONCLUSIONS: Bone was influenced by metabolic patterns associated to amino acids, microbiota co-metabolism and lipid metabolism. Carriers of redox-related variants may benefit from metabolic interventions to prevent the bone frailty consequences based on their antimony, arsenic, selenium, and, possibly, cadmium, exposure levels.PMID:36370960 | DOI:10.1016/j.freeradbiomed.2022.11.007

J Hepatol. 2022 Nov 9:S0168-8278(22)03288-3. doi: 10.1016/j.jhep.2022.10.031. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Acute liver failure (ALF) is a life-threatening disease characterised by high-grade inflammation and immunoparesis with a high incidence of death from sepsis. Here, we aimed to describe the metabolic dysregulation in ALF and determine whether systemic immune responses are modulated via the lysophosphatidylcholine(LPC)-autotaxin(ATX)-lysophosphatidylcholinic acid (LPA) pathway.METHODS: 96 ALF patients, 71 healthy controls (HC), 104 patients with cirrhosis and 31 septic patients were recruited. The pathways of interest were identified based on multivariate statistical analysis of proton nuclear magnetic resonance (1HNMR) spectroscopy, untargeted ultraperformance liquid chromatography-mass spectrometry (UPLC-MS)-based lipidomics and validated with a targeted metabolomics panel. Peripheral blood mononuclear cells were cultured with LPA 16:0, 18:0, 18:1, and their immune checkpoint surface expression was assessed by flow cytometry. LPA receptor (LPAR) transcript-level expression of monocytes was investigated and the effect of LPAR antagonism was also examined in vitro.RESULTS: LPC 16:0 was found highly discriminant between ALF and HC. There was an increase in ATX and LPA in ALF compared to HC and sepsis. LPCs 16:0, 18:0 and 18:1 were reduced in ALF patients with poor prognosis. Treatment of monocytes with LPA 16:0 increased their PD-L1 expression and reduced CD155, CD163, MerTK levels, without effect on T and NK/CD56+T cells immune checkpoints. LPAR1 and 3 antagonism in culture reversed the LPA effect on monocyte expression of MerTK and CD163. MerTK and CD163, but not LPARs genes, were differently expressed and upregulated in monocytes from ALF patients compared to controls.CONCLUSION: Reduced amounts of LPCs are biomarkers of poor prognosis in patients with ALF. The LPC-ATX-LPA axis appears to modulate innate immune response in ALF via LPAR1 and LPAR3. Further investigations are required to identify novel therapeutic agents targeting these receptors.IMPACT AND IMPLICATIONS: Liver disease is the 5th leading cause of death in the UK and rising in incidence. Acute liver failure occurs on the background of normal liver function and mostly in young adults. Acute admissions to hospital and intensive care units are rising in the UK and worldwide. We identified a metabolic signature of acute liver failure and investigated the immunometabolic role of the Lysophosphatdylcholine(LPC)-Autotaxin (ATX)-Lysophosphatidylcholinic acid (LPA) pathway in order to find a mechanistic explanation for monocyte behaviour and find possible therapeutic target(s) to modulate the systemic immune response in ALF. At present, no selective immune based therapies exist. We were able to modulate monocyte phenotype and function in vitro and aim to extend findings to murine models of ALF before could apply this treatment to patients. Future therapies may be based on the enhancement of resolution through metabolic modulation and therefore the role of specific lipids in this pathway require elucidation and the relative merits of ATX inhibition, LPAR blockade or lipid-based therapies answered. This application aims to make a step change in meeting this knowledge gap and definitively elucidate these immune-metabolic pathways using an experimental medicine approach, thus finding the most effective therapeutic targets.PMID:36370949 | DOI:10.1016/j.jhep.2022.10.031

Bioresour Technol. 2022 Nov 9:128301. doi: 10.1016/j.biortech.2022.128301. Online ahead of print.ABSTRACTMicroalgae cannot meet the bait demand for aquaculture due to light intensity limitation and other disadvantageous conditions. This research selected 6 mixotrophic microalgae, and the optimal strains and organic carbon were screened. The results showed that Thalassiosira pseudonana and Chlorella sp. are suitable for mixotrophic culture. The maximum cell density of Thalassiosira pseudonana was found to be 1.67 times than that of the photoautotrophic group when glycerol was added. The maximum cell density of Chlorella sp. with acetic acid was 1.69 times than that of the photoautotrophic group. When the concentration of acetic acid was 5.0 g·L-1 and the concentration of KNO3 was 0.2 g·L-1, the maximum biomass of Chlorella sp. could reach 3.54×107 cells·mL-1; the maximum biomass of Thalassiosira pseudonana was 5.53×106 cells·mL-1 with 10.0 g·L-1 glycerol and 0.2 g·L-1 KNO3. Metabolomic analysis further revealed that mixotrophic bait microalgae could promote the accumulation of lipids and amino acids.PMID:36370937 | DOI:10.1016/j.biortech.2022.128301

J Nutr Biochem. 2022 Nov 9:109214. doi: 10.1016/j.jnutbio.2022.109214. Online ahead of print.ABSTRACTObservational study indicated that folic acid (FA) supplementation may protect against tuberculosis-drug-induced liver injury (TBLI). The aim is to investigate the effect and mechanism of FA on TBLI in rats. Liver injury was induced by a daily gavage of isoniazid (INH) and rifampicin (RIF) in the model and FA groups. Rats in the FA group were also treated with 2.5 mg/kg body weight FA. Rats in the control group were not treated. Eight rats were used in each group. The severity of liver injury was measured by the serum levels of hepatic enzymes and histological score. The metabolites in serum and liver tissues were analyzed by HPLC-Q-TOF-MS/MS. FA treatment significantly reduced alanine aminotransferase and liver necrosis. Seventy-nine differential metabolites in the serum and liver tissues were identified among the three groups. N-acylethanolamines, INH and RIF metabolites, phosphatidylcholines, lysophosphatidylcholines, monoglycerides, diglycerides and bile acids were regulated by FA treatment, involving key metabolic pathways, such as N-acylethanolamine metabolism, INH and RIF metabolism, liver regeneration, inflammation alleviation and bile acid metabolism. RT-PCR and western blotting results confirmed the altered N-acylethanolamine metabolism and improved drug metabolism by FA. In conclusion, FA was protective against TBLI, which may be related to the regulation of N-acylethanolamine metabolism and drug detoxification by FA.PMID:36370928 | DOI:10.1016/j.jnutbio.2022.109214

Phytochemistry. 2022 Nov 9:113508. doi: 10.1016/j.phytochem.2022.113508. Online ahead of print.ABSTRACTThe hop plant (Humulus lupulus L.) has been exploited for a long time for both its brewing and medicinal uses, due in particular to its specific chemical composition. These last years, hop cultivation that was in decline has been experiencing a renewal for several reasons, such as a craze for strongly hopped aromatic beers. In this context, the present work aims at investigating the genetic and chemical diversity of fifty wild hops collected from different locations in Northern France. These wild hops were compared to ten commercial varieties and three heirloom varieties cultivated in the same sampled geographical area. Genetic analysis relying on genome fingerprinting using 11 microsatellite markers showed a high level of diversity. A total of 56 alleles were determined with an average of 10.9 alleles per locus and assessed a significant population structure (mean pairwise FST = 0.29). Phytochemical characterization of hops was based on volatile compound analysis by HS-SPME GC-MS, quantification of the main prenylated phenolic compounds by UHPLC-UV as well as untargeted metabolomics by UHPLC-HRMS and revealed a high level of chemical diversity among the assessed wild accessions. In particular, analysis of volatile compounds revealed the presence of some minor but original compounds, such as aromadendrene, allo-aromadendrene, isoledene, β-guaiene, α-ylangene and β-pinene in some wild accessions; while analysis of phenolic compounds showed high content of β-acids in these wild accessions, up to 2.37% of colupulone. Genetic diversity of wild hops previously observed was hence supported by their chemical diversity. Sample soil analysis was also performed to get a pedological classification of these different collection sites. Results of the multivariate statistical analysis suggest that wild hops constitute a huge pool of chemical and genetic diversity of this species.PMID:36370882 | DOI:10.1016/j.phytochem.2022.113508

Chemosphere. 2022 Nov 9:137213. doi: 10.1016/j.chemosphere.2022.137213. Online ahead of print.ABSTRACTThe biosynthesis of amino acids (AAs) in plants is affected by different nitrogen (N) sources. The effects of exogenous cyanide (KCN) on the concentrations and profiles of AAs in rice seedlings was carried out in the presence of nitrate (+NO3-)/ammonium (+NH4+) or N deficiency (-N). Targeted metabolomics analysis indicated that the highest accumulation of AAs in CN--treated rice seedlings was detected in the "CN-+NH4+" treatments than in other treatments, wherein the doses of exogenous KCN did not significantly affect the total amount of AAs in rice seedlings at the same N fertilized condition. The total content of AAs in rice shoots under "CN-+NH4+" treatments was higher than other treatments, while the total content of AAs in rice roots under "CN-+NO3-" treatments was higher than other treatments. Also, the profiles of 21 AAs in CN--treated rice seedlings showed tissue-specific under different N fertilization. The relative importance index (RII) of AA was used to evaluate the importance of AAs in CN--treated rice seedlings under different N fertilization. The common AAs with higher RII values were compared between three different treatments of KCN (e.g., 0, 1, and 2 mg CN/L). Under "CN-+(-N)" treatments, Ala, Asp, Glu, Val, and Gly (Ala, Gly, Val, and Lys) were the common AAs in rice roots (shoots). Under "CN-+NO3-" treatments, Ala, Glu, Asp, Ser, and Thr (Asp, Ala, Thr, Ser, and Asn) were the common AAs with higher RII values in rice roots (shoots) between all CN- treatments. Under "CN-+NH4+" treatments, Asp, Gln, Asn, and Ala (Asp, Glu, and Thr) are the common AAs with higher RII values in rice roots (shoots) between all CN- treatments. These results suggested that using the RII to describe the change and fluctuation of AAs in rice plants may reflect the different N utilization strategies in response to exogenous CN- exposure.PMID:36370756 | DOI:10.1016/j.chemosphere.2022.137213

Food Chem. 2022 Nov 2;405(Pt A):134807. doi: 10.1016/j.foodchem.2022.134807. Online ahead of print.ABSTRACTFruit of Rosa roxburghii Tratt (FRR) is widely used in functional food industry while short of metabolites research. Herein, we firstly identified 251 metabolites in FRR based on untargeted liquid chromatography-mass spectrometry (LC-MS) approach. Then, 42 differential compounds were sought out to avoid the confusing use of FRR and fruit of R. sterilis S. D. Shi (FRS), and FRR was evaluated exhibiting higher biofunction potential. Moreover, a quantitative LC-MS approach was established to determine the contents of 3 ascorbyl hexosides, and FRR with higher contents should be better source than FRS. Additionally, 17 ascorbic acid (AA) derivatives formed by conjugation of ascorbyl unit with organic acids, flavonoids, or glucuronic acid were also discovered in FRR through characteristic ions of AA and feature-based molecular networking (FBMN), enlightening that AA derivatives were not limited to ascorbyl glycosides. This study provided abundant metabolites information of FRR, laying the basis for exploitation of FRR.PMID:36370576 | DOI:10.1016/j.foodchem.2022.134807

J Ind Microbiol Biotechnol. 2022 Nov 12:kuac025. doi: 10.1093/jimb/kuac025. Online ahead of print.ABSTRACTNitrogen is a critical nutrient in beverage fermentations, influencing fermentation performance and formation of compounds that affect organoleptic properties of the product. Traditionally, most commercial wine fermentations rely on Saccharomyces cerevisiae but the potential of alternative yeasts is increasingly recognised because of the possibility to deliver innovative products and process improvements. In this regard, Saccharomyces uvarum is an attractive non-traditional yeast that, while quite closely related to S. cerevisiae, displays a different fermentative and aromatic profile. Although S. uvarum is used in cider-making and in some winemaking, better knowledge of its physiology and metabolism is required if its full potential is to be realised. To address this gap, we performed a comparative analysis of the response of S. uvarum and S. cerevisiae to 13 different sources of nitrogen, assessing key parameters such as growth, fermentation performance, the production of central carbon metabolites and aroma volatile compounds. We observed that the two species differ in the production of acetate, succinate, medium-chain fatty acids, phenylethanol, phenylethyl acetate and fusel/branched acids in ways that reflect different distribution of fluxes in the metabolic network. The integrated analysis revealed different patterns of yeast performance and activity linked to whether growth was on amino acids metabolised via the Ehrlich pathway or on amino acids and compounds assimilated through the central nitrogen core. This study highlights differences between the two yeasts and the importance that nitrogen metabolism can play in modulating the sensory profile of wine when using S. uvarum as the fermentative yeast.PMID:36370452 | DOI:10.1093/jimb/kuac025

Methods Mol Biol. 2023;2603:163-171. doi: 10.1007/978-1-0716-2863-8_13.ABSTRACTCultured primary neurons are a well-established model for the study of neuronal function. Conventional stable isotope labeling with amino acids in cell culture (SILAC) requires nearly complete metabolic labeling of proteins and therefore is difficult to apply to cultured primary neurons, which do not divide in culture. In a multiplex SILAC strategy, two different sets of heavy amino acids are used for labeling cells for the different experimental conditions. This allows for straightforward SILAC quantitation using partially labeled cells because the two cell populations are always equally labeled. When combined with bioorthogonal noncanonical amino acid tagging (BONCAT), it allows for comparative proteomic analysis of de novo protein synthesis. Here we describe protocols that utilize the multiplex SILAC labeling strategy for primary cultured neurons to study steady-state and nascent proteomes.PMID:36370278 | DOI:10.1007/978-1-0716-2863-8_13

Appl Microbiol Biotechnol. 2022 Nov 12. doi: 10.1007/s00253-022-12261-x. Online ahead of print.ABSTRACTBacterial pathogenicity is greatly affected by nutrient recognition and utilization in the host microenvironment. The characterization of enteral nutrients that promote intestinal pathogen virulence is helpful for developing new adjuvant therapies and inhibiting host damage. Ethanolamine (EA), as a major component of intestinal epithelial cells and bacterial membranes, is abundant in the intestine. Here, we provide the first demonstration that the critical human and porcine pathogen enterotoxigenic Escherichia coli (ETEC) can utilize EA as a nitrogen source, which affects its virulence phenotype. We found that compared with that in M9 medium (containing NH4Cl), EA inhibited ETEC growth to a certain extent; however, the relative expression levels of virulence-related genes, such as ltA (3.0-fold), fimH (2.9-fold), CfaD (2.6-fold), gspD (3.6-fold), and qesE (1.3-fold), increased significantly with 15 mM EA as a nitrogen source (P < 0.05), and the adhesion efficiency of ETEC to Caco-2 cells increased approximately 4.2-fold. In Caco-2 cells, the relative cell viability decreased from 74.8 to 63.4%, and the transepithelial electrical resistance (TEER) cells decreased to 74.8% with intestinal EA (4 mM). In addition, the relative expression levels of proinflammatory factors, such as TNF-α (3.2-fold), INF-γ (2.9-fold), and IL-1β (1.98-fold), in ETEC-infected Caco-2 cells were significantly upregulated (P < 0.05) under EA exposure; however, the above virulence changes were not found in ΔeutR and ΔeutB ETEC. A gas chromatography-mass spectrometry (GC-MS)-based untargeted metabolomics approach was then employed to reveal EA-induced metabolic reprogramming related to ETEC virulence. The data showed that most metabolites related to carbohydrate, aspartate and glutamate metabolism, shikimic acid metabolism, and serine metabolism in ETEC exhibited a decreasing trend with increases in the EA concentration from 0 to 15 mM, but the branched-chain amino acid (BCAA) levels in ETEC increased in a dose-dependent manner under EA exposure. Our data suggest that the intestinal EA concentration can significantly affect the virulence phenotype, metabolic profile, and pathogenicity of ETEC. KEY POINTS: • ETEC growth and virulence gene expression could be regulated by ethanolamine. • The intestinal concentration of EA promoted the damaging effect of ETEC on the host epithelial barrier. • The promoting effect of EA on ETEC toxicity may be related to BCAA metabolism.PMID:36370159 | DOI:10.1007/s00253-022-12261-x

Clin Pharmacol Ther. 2022 Nov 12. doi: 10.1002/cpt.2794. Online ahead of print.ABSTRACTIntravenous (IV) busulfan doses are often personalized to a target plasma exposure (targeted busulfan) using an individual's busulfan clearance (BuCL). We evaluated whether BuCL could be predicted by a predose plasma panel of 841 endogenous metabolomic compounds (EMCs). In this prospective cohort of 132 hematopoietic cell transplant (HCT) patients, all had samples collected immediately before to busulfan administration (preBU) and 96 had samples collected two weeks before busulfan (2-week-preBU). BuCL was significantly associated with 37 EMCs after univariate linear regression analysis and controlling for false discovery (<0.05) in the 132 preBU samples. In parallel, with preBU samples, we included all 841 EMCs in a Lasso penalized regression which selected 13 EMCs as predominantly associated with BuCL. Then, we constructed a prediction model by estimating coefficients for these 13 EMCs, along with sex, using ordinary least-squares. When the resulting linear prediction model was applied to the 2-week-preBU samples, it explained 40% of the variation in BuCL (adjusted R2 =0.40). Pathway enrichment analysis revealed 18 pathways associated with BuCL. Lysine degradation followed by Steroid Biosynthesis, which aligned with the univariate analysis, were the top two pathways. BuCL can be predicted before busulfan administration with a linear regression model of 13 EMCs. This pharmacometabolomics method should be prioritized over use of a busulfan test dose or pharmacogenomics to guide busulfan dosing. These results highlight the potential of pharmacometabolomics as a precision medicine tool to improve or replace pharmacokinetics to personalize busulfan doses.PMID:36369996 | DOI:10.1002/cpt.2794