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

Adults prenatally exposed to the Dutch Famine exhibit a metabolic signature associated with a broad spectrum of common diseases

Thu, 18/04/2024 - 12:00
medRxiv [Preprint]. 2024 Apr 5:2024.04.04.24305284. doi: 10.1101/2024.04.04.24305284.ABSTRACTBACKGROUND: Exposure to famine in the prenatal period is associated with an increased risk of metabolic disease, including obesity and type-2 diabetes. We employed nuclear magnetic resonance (NMR) metabolomic profiling to provide a deeper insight into the metabolic changes associated with survival of prenatal famine exposure during the Dutch Famine at the end of World War II and explore their link to disease.METHODS: NMR metabolomics data were generated from serum in 480 individuals prenatally exposed to famine (mean 58.8 years, 0.5 SD) and 464 controls (mean 57.9 years, 5.4 SD). We tested associations of prenatal famine exposure with levels of 168 individual metabolic biomarkers and compared the metabolic biomarker signature of famine exposure with those of 154 common diseases.RESULTS: Prenatal famine exposure was associated with higher concentrations of branched-chain amino acids ((iso)-leucine), aromatic amino acid (tyrosine), and glucose in later life (0.2-0.3 SD, p < 3×10 -3 ). The metabolic biomarker signature of prenatal famine exposure was positively correlated to that of incident type-2 diabetes (r = 0.77, p = 3×10 -27 ), also when re-estimating the signature of prenatal famine exposure among individuals without diabetes (r = 0.67, p = 1×10 -18 ). Remarkably, this association extended to 115 common diseases for which signatures were available (0.3 :< r :< 0.9, p < 3.2×10 -4 ). Correlations among metabolic signatures of famine exposure and disease outcomes were attenuated when the famine signature was adjusted for body mass index.CONCLUSIONS: Prenatal famine exposure is associated with a metabolic biomarker signature that strongly resembles signatures of a diverse set of diseases, an observation that can in part be attributed to a shared involvement of obesity.PMID:38633796 | PMC:PMC11023671 | DOI:10.1101/2024.04.04.24305284

Metabolomics Signatures of serotonin reuptake inhibitor (Escitalopram), serotonin norepinephrine reuptake inhibitor (Duloxetine) and Cognitive Behavior Therapy on Key Neurotransmitter Pathways in Major Depressive Disorder

Thu, 18/04/2024 - 12:00
medRxiv [Preprint]. 2024 Apr 3:2024.04.02.24304677. doi: 10.1101/2024.04.02.24304677.ABSTRACTMetabolomics provides powerful tools that can inform about heterogeneity in disease and response to treatments. In this study, we employed an electrochemistry-based targeted metabolomics platform to assess the metabolic effects of three randomly-assigned treatments: escitalopram, duloxetine, and Cognitive Behavior Therapy (CBT) in 163 treatment-naïve outpatients with major depressive disorder. Serum samples from baseline and 12 weeks post-treatment were analyzed using targeted liquid chromatography-electrochemistry for metabolites related to tryptophan, tyrosine metabolism and related pathways. Changes in metabolite concentrations related to each treatment arm were identified and compared to define metabolic signatures of exposure. In addition, association between metabolites and depressive symptom severity (assessed with the 17-item Hamilton Rating Scale for Depression [HRSD 17 ]) and anxiety symptom severity (assessed with the 14-item Hamilton Rating Scale for Anxiety [HRSA 14 ]) were evaluated, both at baseline and after 12 weeks of treatment. Significant reductions in serum serotonin level and increases in tryptophan-derived indoles that are gut bacterially derived were observed with escitalopram and duloxetine arms but not in CBT arm. These include indole-3-propionic acid (I3PA), indole-3-lactic acid (I3LA) and Indoxyl sulfate (IS), a uremic toxin. Purine-related metabolites were decreased across all arms. Different metabolites correlated with improved symptoms in the different treatment arms revealing potentially different mechanisms between response to antidepressant medications and to CBT.PMID:38633777 | PMC:PMC11023644 | DOI:10.1101/2024.04.02.24304677

Classification of grape seed residues from distillation industries in Europe according to the polyphenol composition highlights the influence of variety, geographical origin and color

Thu, 18/04/2024 - 12:00
Food Chem X. 2024 Apr 7;22:101362. doi: 10.1016/j.fochx.2024.101362. eCollection 2024 Jun 30.ABSTRACTGrape seed residues represent the raw material to produce several value-added products including polyphenol-rich extracts with nutritional and health attributes. Although the impact of variety and environmental conditions on the polyphenol composition in fresh berries is recognized, no data are available regarding grape seed residues. The chemical composition of grape seed residues from wine distilleries in France, Spain and Italy was characterized by mass spectrometry. Forty-two metabolites were identified belonging to non-galloylated and galloylated procyanidins as well as amino acids. Polyphenol concentrations in the red varieties originated from Champagne or Veneto were twice higher than in white varieties from the Loire Valley. The chemical profiles of grape seed residues were mainly classified according to the color variety with galloylated procyanidins as biomarkers of white varieties and non-galloylated procyanidins as biomarkers of red ones. The present approach might assist the selection of grape seed residues as quality raw materials for the production of polyphenol-rich extracts.PMID:38633739 | PMC:PMC11021364 | DOI:10.1016/j.fochx.2024.101362

Aptly chosen, effectively emphasizing the action and mechanism of antimycin A<sub>1</sub>

Thu, 18/04/2024 - 12:00
Front Microbiol. 2024 Apr 3;15:1371850. doi: 10.3389/fmicb.2024.1371850. eCollection 2024.ABSTRACTRhizoctonia solani Kühn, a plant pathogenic fungus that can cause diseases in multiple plant species is considered one of the common and destructive pathogens in many crops. This study investigated the action of antimycin A1, which was isolated from Streptomyces AHF-20 found in the rhizosphere soil of an ancient banyan tree, on Rhizoctonia solani and its mechanism. The inhibitory effect of antimycin A1 on R. solani was assessed using the comparative growth rate method. The results revealed that antimycin A1 exhibited a 92.55% inhibition rate against R. solani at a concentration of 26.66 μg/mL, with an EC50 value of 1.25 μg/mL. To observe the impact of antimycin A1 on mycelial morphology and ultrastructure, the fungal mycelium was treated with 6.66 μg/mL antimycin A1, and scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were employed. SEM analysis demonstrated that antimycin A1 caused mycelial morphology to become stripped, rough, and folded. The mycelium experienced severe distortion and breakage, with incomplete or locally enlarged ends, shortened branches, and reduced numbers. TEM observation revealed thickened cell walls, indistinct organelle boundaries, swollen mitochondria, exosmotic substances in vesicles, slow vesicle fusion, and cavitation. Real-time quantitative PCR and enzyme activity assays were conducted to further investigate the impact of antimycin A1 on mitochondria. The physiological and biochemical results indicated that antimycin A1 inhibited complexes III and IV of the mitochondrial electron transport chain. RT-PCR analysis demonstrated that antimycin A1 controlled the synthesis of relevant enzymes by suppressing the transcription levels of ATP6, ATP8, COX3, QCR6, CytB, ND1, and ND3 genes in mitochondria. Additionally, a metabolomic analysis revealed that antimycin A1 significantly impacted 12 metabolic pathways. These pathways likely experienced alterations in their metabolite profiles due to the inhibitory effects of antimycin A1. Consequently, the findings of this research contribute to the potential development of novel fungicides.PMID:38633707 | PMC:PMC11021728 | DOI:10.3389/fmicb.2024.1371850

Impact of <em>Pediococcus acidilactici</em> GLP06 supplementation on gut microbes and metabolites in adult beagles: a comparative analysis

Thu, 18/04/2024 - 12:00
Front Microbiol. 2024 Apr 3;15:1369402. doi: 10.3389/fmicb.2024.1369402. eCollection 2024.ABSTRACTThere is growing interest in the potential health benefits of probiotics for both humans and animals. The study aimed to investigate the effects of feeding the canine-derived probiotic Pediococcus acidilactici GLP06 to adult beagles by analysing the microbiome and metabolome. Twenty-four healthy adult beagles were randomly assigned to four groups. The CK group received a standard diet, while the three probiotic groups, the LG group (2 × 108 CFU/day/dog), MG group (2 × 109 CFU/day/dog), and HG group (2 × 1010 CFU/day/dog), received the standard diet supplemented with varying amounts of probiotics. The results show that, compared to the CK group, total antioxidant capacity was significantly increased in the MG and HG groups (p < 0.05), and superoxide dismutase and catalase were significantly increased in the HG group (p < 0.05). Compared to the CK group, malondialdehyde and blood urea nitrogen content were significantly decreased in the MG and HG groups (p < 0.05). Additionally, secretory immunoglobulin A activity was significantly increased in the HG group compared to the CK and LG groups (p < 0.05), and immunoglobulin G activity was significantly increased in the HG group compared to the CK, LG, and MG groups (p < 0.05). In addition, compared with the CK group, the abundance of Faecalitalea and Collinsella increased in the LG group, and the relative abundance of Tyzzerella and Parasutterella increased in the MG group. The α diversity and the relative abundances of beneficial bacteria (Faecalibacterium, Lachnospiraceae_NK4A1316, and Ruminococcaceae_UCG-005) were higher in the HG group than in the CK group. Furthermore, acetic acid content was significantly increased in the HG group compared to the CK, LG, and MG groups (p < 0.05). Butyric acid, isobutyric acid, and the total SCFA content were significantly increased in the HG group compared to the CK group (p < 0.05). Moreover, metabolome analysis revealed 111 upregulated and 171 downregulated metabolites in the HG group. In conclusion, this study presents evidence that supplementing with P. acidilactici GLP06 can have a positive impact on antioxidant activity, immunoproteins, SCFAs, and gut microbiota in adult beagles. These findings highlight the potential of probiotics as a dietary intervention to enhance gut health and overall wellbeing in companion animals.PMID:38633690 | PMC:PMC11021720 | DOI:10.3389/fmicb.2024.1369402

Metabolomics of Mice with Type 2 Diabetes and Nonalcoholic Fatty Liver Treated by Acupuncture

Thu, 18/04/2024 - 12:00
Int J Endocrinol. 2024 Apr 10;2024:5568337. doi: 10.1155/2024/5568337. eCollection 2024.ABSTRACTINTRODUCTION: To investigate the effects of acupuncture on endogenous metabolites in the liver of type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD) mice-based metabolomics.METHODS: Proton nuclear magnetic resonance (1H-NMR) metabolomics combined with multivariate statistical analysis and univariate analysis were used to analyze the changes of endogenous metabolites in the liver of mice in each group and to provide new clinical ideas for acupuncture in the treatment of glycolipid metabolism disorders caused by T2DM and NAFLD.RESULTS: After 4 weeks of continuous treatment, fasting blood glucose (FBG), insulin (INS), total cholesterol (TC), and triglyceride (TG) decreased significantly in mice in the acupuncture treatment group (ATG), and the content of liver glycogen increased significantly. Based on 1H-NMR metabolomic analysis, a total of 47 metabolites were identified in the liver of T2DM with NAFLD mice, of which eight metabolites: UDP-N-acetylglucosamine, adenosine, glutamate, isoleucine, ATP, 3-hydroxybutyric acid, NADP+, and leucine were significantly altered by acupuncture treatment. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, it is found that acupuncture has an intervention effect on five metabolic pathways, mainly involving amino acid metabolism, energy metabolism, and oxidative stress.CONCLUSION: Our study shows that acupuncture can regulate the liver metabolism mode of T2DM in NAFLD mice. It can reduce blood glucose and lipid accumulation in the liver, and these findings provide a new idea and theoretical basis for acupuncture in the treatment of diseases related to glucose and lipid metabolism.PMID:38633528 | PMC:PMC11023731 | DOI:10.1155/2024/5568337

Silicon nanoparticles <em>vs</em> trace elements toxicity: <em>Modus operandi</em> and its omics bases

Thu, 18/04/2024 - 12:00
Front Plant Sci. 2024 Apr 3;15:1377964. doi: 10.3389/fpls.2024.1377964. eCollection 2024.ABSTRACTPhytotoxicity of trace elements (commonly misunderstood as 'heavy metals') includes impairment of functional groups of enzymes, photo-assembly, redox homeostasis, and nutrient status in higher plants. Silicon nanoparticles (SiNPs) can ameliorate trace element toxicity. We discuss SiNPs response against several essential (such as Cu, Ni, Mn, Mo, and Zn) and non-essential (including Cd, Pb, Hg, Al, Cr, Sb, Se, and As) trace elements. SiNPs hinder root uptake and transport of trace elements as the first line of defence. SiNPs charge plant antioxidant defence against trace elements-induced oxidative stress. The enrolment of SiNPs in gene expressions was also noticed on many occasions. These genes are associated with several anatomical and physiological phenomena, such as cell wall composition, photosynthesis, and metal uptake and transport. On this note, we dedicate the later sections of this review to support an enhanced understanding of SiNPs influence on the metabolomic, proteomic, and genomic profile of plants under trace elements toxicity.PMID:38633451 | PMC:PMC11021597 | DOI:10.3389/fpls.2024.1377964

Exploration of exogenous chlorogenic acid as a potential plant stimulant: enhancing physiochemical properties in <em>Lonicera japonica</em>

Thu, 18/04/2024 - 12:00
Physiol Mol Biol Plants. 2024 Mar;30(3):453-466. doi: 10.1007/s12298-024-01435-8. Epub 2024 Mar 20.ABSTRACTIn this study, we applied exogenous chlorogenic acid (CGA) to Lonicera japonica (L. japonica) leaves via foliar sprays every Monday, Wednesday, and Friday for a period of 12 months. Our continuous monitoring over this period revealed a consistent increase in flavonoid levels from the second to the tenth month following the commencement of CGA treatment. This was accompanied by a notable upregulation in the expression of four secondary metabolite-related enzyme genes: LjPAL1, LjPAL2, LjPAL3, and LjISY1. Concurrently, there was a significant enhancement in the total activity of the enzyme phenylalanine ammonia-lyase. The total antioxidant capacity of the plants also showed a marked increase from the third to the seventh month post-treatment initiation, subsequently stabilizing. This increase was also reflected in the elevated activities of key antioxidant enzymes: peroxidase, polyphenol oxidase, and superoxide dismutase. Furthermore, the treatment notably enhanced various indicators of nutrient growth, such as total protein content, total sugar content, and leaf area. Notably, the relative expression of LjTF1, a kind of BZIP transcription factor gene known for its extensive regulatory effects, showed a significant and sustained increase after the start of exogenous CGA treatment. Subsequent metabolomic analysis revealed significant changes in L. japonica metabolites. Specifically, 172 differentially expressed metabolites (DEMs) showed a notable increase (Fold > 1), predominantly in pathways related to nutrient metabolism such as carbohydrate, amino acid, and energy metabolism. Notably, some of the highly expressed DEMs (Fold > 4) are key antioxidants and medicinal components in L. japonica. The experimental findings were in alignment with the metabolomics analysis, indicating that exogenous CGA can act as a stimulant for L. japonica. It promotes the significant accumulation of certain secondary metabolites, enhances nutritive growth, and boosts the plant's total antioxidant capacity.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-024-01435-8.PMID:38633274 | PMC:PMC11018593 | DOI:10.1007/s12298-024-01435-8

Boosting the immunogenicity of the CoronaVac SARS-CoV-2 inactivated vaccine with Huoxiang Suling Shuanghua Decoction: a randomized, double-blind, placebo-controlled study

Thu, 18/04/2024 - 12:00
Front Immunol. 2024 Apr 3;15:1298471. doi: 10.3389/fimmu.2024.1298471. eCollection 2024.ABSTRACTINTRODUCTION: In light of the public health burden of the COVID-19 pandemic, boosting the safety and immunogenicity of COVID-19 vaccines is of great concern. Numerous Traditional Chinese medicine (TCM) preparations have shown to beneficially modulate immunity. Based on pilot experiments in mice that showed that supplementation with Huoxiang Suling Shuanghua Decoction (HSSD) significantly enhances serum anti-RBD IgG titers after inoculation with recombinant SARS-CoV-2 S-RBD protein, we conducted this randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the potential immunogenicity boosting effect of oral HSSD after a third homologous immunization with Sinovac's CoronaVac SARS-CoV-2 (CVS) inactivated vaccine.METHODS: A total of 70 participants were randomly assigned (1:1 ratio) to receive a third dose of CVS vaccination and either oral placebo or oral HSSD for 7 days. Safety aspects were assessed by recording local and systemic adverse events, and by blood and urine biochemistry and liver and kidney function tests. Main outcomes evaluated included serum anti-RBD IgG titer, T lymphocyte subsets, serum IgG and IgM levels, complement components (C3 and C4), and serum cytokines (IL-6 and IFN-γ). In addition, metabolomics technology was used to analyze differential metabolite expression after supplementation with HSSD.RESULTS: Following a third CVS vaccination, significantly increased serum anti-RBD IgG titer, reduced serum IL-6 levels, increased serum IgG, IgM, and C3 and C4 levels, and improved cellular immunity, evidenced by reduce balance deviations in the distribution of lymphocyte subsets, was observed in the HSSD group compared with the placebo group. No serious adverse events were recorded in either group. Serum metabolomics results suggested that the mechanisms by which HSSD boosted the immunogenicity of the CVS vaccine are related to differential regulation of purine metabolism, vitamin B6 metabolism, folate biosynthesis, arginine and proline metabolism, and steroid hormone biosynthesis.CONCLUSION: Oral HSSD boosts the immunogenicity of the CVS vaccine in young and adult individuals. This trial provides clinical reference for evaluation of TCM immunomodulators to improve the immune response to COVID-19 vaccines.PMID:38633263 | PMC:PMC11021573 | DOI:10.3389/fimmu.2024.1298471

Immune system-related plasma extracellular vesicles in healthy aging

Thu, 18/04/2024 - 12:00
Front Immunol. 2024 Apr 3;15:1355380. doi: 10.3389/fimmu.2024.1355380. eCollection 2024.ABSTRACTOBJECTIVES: To identify age-related plasma extracellular vehicle (EVs) phenotypes in healthy adults.METHODS: EV proteomics by high-resolution mass spectrometry to evaluate EV protein stability and discover age-associated EV proteins (n=4 with 4 serial freeze-thaws each); validation by high-resolution flow cytometry and EV cytokine quantification by multiplex ELISA (n=28 healthy donors, aged 18-83 years); quantification of WI-38 fibroblast cell proliferation response to co-culture with PKH67-labeled young and old plasma EVs. The EV samples from these plasma specimens were previously characterized for bilayer structure, intra-vesicle mitochondria and cytokines, and hematopoietic cell-related surface markers.RESULTS: Compared with matched exo-EVs (EV-depleted supernatants), endo-EVs (EV-associated) had higher mean TNF-α and IL-27, lower mean IL-6, IL-11, IFN-γ, and IL-17A/F, and similar mean IL-1β, IL-21, and IL-22 concentrations. Some endo-EV and exo-EV cytokine concentrations were correlated, including TNF-α, IL-27, IL-6, IL-1β, and IFN-γ, but not IL-11, IL-17A/F, IL-21 or IL-22. Endo-EV IFN-γ and exo-EV IL-17A/F and IL-21 declined with age. By proteomics and confirmed by flow cytometry, we identified age-associated decline of fibrinogen (FGA, FGB and FGG) in EVs. Age-related EV proteins indicated predominant origins in the liver and innate immune system. WI-38 cells (>95%) internalized similar amounts of young and old plasma EVs, but cells that internalized PKH67-EVs, particularly young EVs, underwent significantly greater cell proliferation.CONCLUSION: Endo-EV and exo-EV cytokines function as different biomarkers. The observed healthy aging EV phenotype reflected a downregulation of EV fibrinogen subpopulations consistent with the absence of a pro-coagulant and pro-inflammatory condition common with age-related disease.PMID:38633262 | PMC:PMC11021711 | DOI:10.3389/fimmu.2024.1355380

Mast cells and histamine in cholangiocarcinoma: exploring overlooked avenues for enhanced patient management

Wed, 17/04/2024 - 12:00
Gut. 2024 Apr 17:gutjnl-2024-332288. doi: 10.1136/gutjnl-2024-332288. Online ahead of print.NO ABSTRACTPMID:38631898 | DOI:10.1136/gutjnl-2024-332288

Defining predictors of responsiveness to advanced therapies in Crohn's disease and ulcerative colitis: protocol for the IBD-RESPONSE and nested CD-metaRESPONSE prospective, multicentre, observational cohort study in precision medicine

Wed, 17/04/2024 - 12:00
BMJ Open. 2024 Apr 17;14(4):e073639. doi: 10.1136/bmjopen-2023-073639.ABSTRACTINTRODUCTION: Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient's quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%. A significant challenge is an inability to predict which treatment will benefit individual patients.Current understanding of IBD pathogenesis implicates complex interactions between host genetics and the gut microbiome. Most cohorts studying the gut microbiota to date have been underpowered, examined single treatments and produced heterogeneous results. Lack of cross-treatment comparisons and well-powered independent replication cohorts hampers the ability to infer real-world utility of predictive signatures.IBD-RESPONSE will use multi-omic data to create a predictive tool for treatment response. Future patient benefit may include development of biomarker-based treatment stratification or manipulation of intestinal microbial targets. IBD-RESPONSE and downstream studies have the potential to improve quality of life, reduce patient risk and reduce expenditure on ineffective treatments.METHODS AND ANALYSIS: This prospective, multicentre, observational study will identify and validate a predictive model for response to advanced IBD therapies, incorporating gut microbiome, metabolome, single-cell transcriptome, human genome, dietary and clinical data. 1325 participants commencing advanced therapies will be recruited from ~40 UK sites. Data will be collected at baseline, week 14 and week 54. The primary outcome is week 14 clinical response. Secondary outcomes include clinical remission, loss of response in week 14 responders, corticosteroid-free response/remission, time to treatment escalation and change in patient-reported outcome measures.ETHICS AND DISSEMINATION: Ethical approval was obtained from the Wales Research Ethics Committee 5 (ref: 21/WA/0228). Recruitment is ongoing. Following study completion, results will be submitted for publication in peer-reviewed journals and presented at scientific meetings. Publications will be summarised at www.ibd-response.co.uk.TRIAL REGISTRATION NUMBER: ISRCTN96296121.PMID:38631839 | DOI:10.1136/bmjopen-2023-073639

Targeted and non-targeted mass spectrometry to explore the chemical diversity of the genus Gambierdiscus in the Atlantic Ocean

Wed, 17/04/2024 - 12:00
Phytochemistry. 2024 Apr 15:114095. doi: 10.1016/j.phytochem.2024.114095. Online ahead of print.ABSTRACTDinoflagellates of the genus Gambierdiscus have been associated with ciguatera, the most common non-bacterial fish-related intoxication in the world. Many studies report the presence of potentially toxic Gambierdiscus species along the Atlantic coasts including G. australes, G. silvae and G. excentricus. Estimates of their toxicity, as determined by bio-assays, vary substantially, both between species and strains of the same species. Therefore, there is a need for additional knowledge on the metabolite production of Gambierdiscus species and their variation to better understand species differences. Using liquid chromatography coupled to mass spectrometry, toxin and metabolomic profiles of five species of Gambierdiscus found in the Atlantic Ocean were reported. In addition, a molecular network was constructed aiming at annotating the metabolomes. Results demonstrated that G. excentricus could be discriminated from the other species based solely on the presence of MTX4 and sulfo-gambierones and that the variation in toxin content for a single strain could be up to a factor of two due to different culture conditions between laboratories. While untargeted analyses highlighted a higher variability at the metabolome level, signal correction was applied and supervised multivariate statistics performed on the untargeted data set permitted the selection of 567 features potentially useful as biomarkers for the distinction of G. excentricus, G. caribaeus, G. carolinianus, G. silvae and G. belizeanus. Further studies will be required to validate the use of these biomarkers in discriminating Gambierdiscus species. The study also provided an overview about 17 compound classes present in Gambierdiscus, however, significant improvements in annotation are still required to reach a more comprehensive knowledge of Gambierdiscus' metabolome.PMID:38631521 | DOI:10.1016/j.phytochem.2024.114095

Lactate Oxidation in Paracoccus denitrificans

Wed, 17/04/2024 - 12:00
Arch Biochem Biophys. 2024 Apr 15:109988. doi: 10.1016/j.abb.2024.109988. Online ahead of print.ABSTRACTParacoccus denitrificans has a classical cytochrome-dependent electron transport chain and two alternative oxidases. The classical transport chain is very similar to that in eukaryotic mitochondria. Thus, P. denitrificans can serve as a model of the mammalian mitochondrion that may be more tractable in elucidating mechanisms of regulation of energy production than are mitochondria. In a previous publication we reported detailed studies on respiration in P. denitrificans grown aerobically on glucose or malate. We noted that P. denitrificans has large stores of lactate under various growth conditions. This is surprising because P. denitrificans lacks an NAD+ dependent lactate dehydrogenase. The aim of this study was to investigate the mechanisms of lactate oxidation in P. denitrificans . We found that the bacterium grows well on either D-lactate or L-lactate. Growth on lactate supported a rate of maximum respiration that was equal to that of cells grown on glucose or malate. We report proteomic, metabolomic, and biochemical studies that establish that the metabolism of lactate by P. denitrificans is mediated by two non-NAD-dependent lactate dehydrogenases. One prefers D-lactate over L-lactate (D-iLDH) and the other prefers L-lactate (L-iLDH). We cloned and produced the D-iLDH and characterized it. The Km for D-lactate was 34 μM, and for L-lactate it was 3.7 mM. Pyruvate was not a substrate, rendering the reaction unidirectional with lactate being converted to pyruvate for entry into the TCA cycle. The intracellular lactate was ∼14 mM such that both isomers could be metabolized by the enzyme. The enzyme has 1 FAD per molecule and utilizes a quinone rather than NAD+ as an electron acceptor. D-iLDH provides a direct entry of lactate reducing equivalents into the cytochrome chain, potentially explaining the high respiratory capacity of P. denitrificans in the presence of lactate.PMID:38631502 | DOI:10.1016/j.abb.2024.109988

Metabolomic reveals the responses of sludge properties and microbial communities to high nitrite stress in denitrifying phosphorus removal systems

Wed, 17/04/2024 - 12:00
Environ Res. 2024 Apr 15:118924. doi: 10.1016/j.envres.2024.118924. Online ahead of print.ABSTRACTNitrite, as an electron acceptor, plays a good role in denitrifying phosphorus removal (DPR); however, high nitrite concentration has adverse affects on sludge performance. We investigated the precise mechanisms of responses of sludge to high nitrite stress, including surface characteristics, intracellular and extracellular components, microbial and metabolic responses. When the nitrite stress reached 90 mg/L, the sludge settling performance was improved, but the activated sludge was aging. FTIR and XPS analysis revealed a significant increase in the hydrophobicity of the sludge, resulting in improve settling performance. However, the intracellular carbon sources synthesis was inhibited. In addition, the components in the tightly bound extracellular polymeric substances (TB-EPS) of sludge were significantly reduced and indicated the disturb of metabolism. Notably, Exiguobacterium emerged as a new genus when face high nitrite stress that could maintaining survival in hostile environments. Moreover, metabolomic analysis demonstrated strong biological response to nitrite stress further supported above results that include the inhibited of carbohydrate and amino acid metabolism. More importantly, some lipids (PS, PA, LysoPA, LysoPC and LysoPE) were significantly upregulated that related enhanced membrane lipid remodeling. The comprehensive analyses provide novel insights into the high nitrite stress responses mechanisms in activated sludge systems.PMID:38631473 | DOI:10.1016/j.envres.2024.118924

The Association of Infant Urinary Adrenal Steroids with the Risk of Childhood Asthma Development

Wed, 17/04/2024 - 12:00
Ann Allergy Asthma Immunol. 2024 Apr 15:S1081-1206(24)00215-1. doi: 10.1016/j.anai.2024.04.008. Online ahead of print.ABSTRACTBACKGROUND: Adrenal steroids play important roles in early life development. However, our understanding of the effects of perinatal adrenal steroids on the development of childhood asthma is incomplete.OBJECTIVE: This study aimed to evaluate the associations between early life adrenal steroid levels and childhood asthma.METHODS: Participants included INSPIRE birth cohort children with untargeted urinary metabolomics data measured during early infancy (n=264) and nasal immune mediator data measured concurrently at age 2-6 months (n=76). A total of 11 adrenal steroid compounds identified using untargeted metabolomics and 6 asthma-relevant nasal immune mediators from multiplex assays were a priori selected. Current asthma at ages 5 and 6 years was ascertained using validated questionnaires. Associations were tested using logistic and linear regression with confounders adjustment.RESULTS: Pregnenetriol disulfate (adjusted odd ratio, aOR= 0.20, 95%CI= [0.06, 0.68]) and 3a,21-dihydroxy-5b-pregnane-11,20-dione-21-glucuronide (aOR= 0.34, 95%CI= [0.14, 0.75]) were inversely associated with childhood asthma at 5 and 6 years after multiple testing adjustment. There was a significant interaction effect of pregnanediol-3-glucuronide by sex (aOR=0.11, 95%CI=[0.02, 0.51], for females) on childhood asthma. Pregnenetriol disulfate was inversely associated with GM-CSF (b=-0.45, q-value=0.05). 3a,21-dihydroxy-5b-pregnane-11,20-dione 21-glucuronide was inversely associated with IL-4 (b=-0.29, q-value=0.02), IL-5 (b=-0.35, q-value=0.006), IL-13 (b=-0.26, q-value=0.02), GM-CSF (b=-0.35, q-value=0.006), and FGF-b(b=-0.24, q-value=0.01) after multiple testing adjustment.CONCLUSION: The inverse association between adrenal steroids downstream of progesterone and 17-hydroxypregnenolone and odds of childhood asthma and nasopharyngeal Type 2 immune biomarkers suggest that increased early life adrenal steroids may suppress Type 2 inflammation and protect against the development of childhood asthma.PMID:38631429 | DOI:10.1016/j.anai.2024.04.008

Recent advances in understanding the fitness and survival mechanisms of Vibrio parahaemolyticus

Wed, 17/04/2024 - 12:00
Int J Food Microbiol. 2024 Apr 5;417:110691. doi: 10.1016/j.ijfoodmicro.2024.110691. Online ahead of print.ABSTRACTThe presence of Vibrio parahaemolyticus (Vp) in different production stages of seafood has generated negative impacts on both public health and the sustainability of the industry. To further better investigate the fitness of Vp at the phenotypical level, a great number of studies have been conducted in recent years using plate counting methods. In the meantime, with the increasing accessibility of the next generation sequencing and the advances in analytical chemistry techniques, omics-oriented biotechnologies have further advanced our knowledge in the survival and virulence mechanisms of Vp at various molecular levels. These observations provide insights to guide the development of novel prevention and control strategies and benefit the monitoring and mitigation of food safety risks associated with Vp contamination. To timely capture these recent advances, this review firstly summarizes the most recent phenotypical level studies and provide insights about the survival of Vp under important in vitro stresses and on aquatic products. After that, molecular survival mechanisms of Vp at transcriptomic and proteomic levels are summarized and discussed. Looking forward, other newer omics-biotechnology such as metabolomics and secretomics show great potential to be used for confirming the cellular responses of Vp. Powerful data mining tools from the field of machine learning and artificial intelligence, that can better utilize the omics data and solve complex problems in the processing, analysis, and interpretation of omics data, will further improve our mechanistic understanding of Vp.PMID:38631283 | DOI:10.1016/j.ijfoodmicro.2024.110691

Dietary supplementation with ellagic acid improves the growth performance, meat quality, and metabolomics profile of yellow-feathered broiler chickens

Wed, 17/04/2024 - 12:00
Poult Sci. 2024 Mar 30;103(6):103700. doi: 10.1016/j.psj.2024.103700. Online ahead of print.ABSTRACTThe aim of this research was to explore the effects of ellagic acid (EA) on growth performance, meat quality, and metabolomics profile of broiler chickens. 240 healthy yellow-feathered broilers were randomly divided into 4 groups (6 replicates/group and 10 broilers /replicate): 1) a standard diet (CON); 2) CON+0.01% EA; 3) CON+0.02% EA; 4) CON+0.04% EA. Compared with the CON group, dietary 0.02% EA increased linearly and quadratically the ADG and lowered F/G ratio from 29 to 56 d and from 1 to 56 d of age (P < 0.05). The EA groups had higher spleen index and showed linear and quadratic improve thymus index (P < 0.05). A total of 0.02% EA linearly and quadratically increased the leg muscle percentage and quadratically increased the breast muscle percentage (P < 0.05). Compared to the control diet, 0.02% EA decreased quadratically the L* and increased a* of breast muscle at 45 min postslaughter (P < 0.05), and quadratically decreased (P < 0.05) the b* and increased linearly and quadratically (P < 0.05) drip loss. Additionally, EA improved linearly and quadratically (P < 0.05) serum total protein concentration and reduced linearly and quadratically (P < 0.05) serum blood urea nitrogen concentration. A total of 0.02% EA quadratically increased catalase activity and decreased malondialdehyde concentration in breast muscle compared with the control diet (P < 0.05). 0.02% and 0.04% EA could linearly and quadratically increase (P < 0.05) the concentrations of histidine, leucine and essential amino acids (EAA), 0.02% EA could linearly and quadratically increase (P < 0.05) the concentrations of threonine, glutamate, and flavored amino acids in breast muscle. 0.02% EA linearly and quadratically improved the C20:3n6, C22:6n3, polyunsaturated fatty acid (PUFA) concentrations, and the ratio of PUFA to saturated fatty acids (SFA), but reduced the C16:0 and the SFA concentrations in breast muscle than the CON group (P < 0.05). The EA diet linearly increased (P = 0.035) and quadratically tended (P = 0.068) to regulate the C18:2n6c concentration of breast muscle. Metabolomics showed that alanine metabolism, aspartate and glutamate metabolism, arginine and proline metabolism, taurine and hypotaurine metabolism, and glycerophospholipid metabolism were the most differentially abundant. These results showed that EA supported moderate positive effects on growth performance, meat quality, and metabolomics profile of broilers.PMID:38631231 | DOI:10.1016/j.psj.2024.103700

Multiple metabolite profiles uncover remarkable bioactive compounds and metabolic characteristics of noni fruit (Morinda citrifolia L.) at various stages of ripeness

Wed, 17/04/2024 - 12:00
Food Chem. 2024 Apr 13;450:139357. doi: 10.1016/j.foodchem.2024.139357. Online ahead of print.ABSTRACTThis study aimed to investigate the changes in physicochemical properties, bioactive compounds, and metabolic characteristics of noni fruit at different ripeness levels. The results showed that there were significant differences in physicochemical properties. HPLC analysis was conducted, revealing succinic acid, scopoletin, deacetylasperulosidic acid, and asperulosidic acid were key bioactive compounds as the fruit ripened. Additionally, 4 differentbiomarkers (isocitric acid, 4,4-thiodiphenol, lobaric acid, and octocrylene), identified using 1HNMR and LC-IT-TOF-MS, were found to have a VIP value over 1. The results from HS-GC-IMS demonstrated noteworthy that 14 volatile compounds were identified as highly discriminative features during fruit ripening. Furthermore, correlation analysis showed that different ripeness had significant effects on bioactive components and functional activities, e.g., the inhibition rate of enzyme and E. coli of noni fruit with different ripeness exceeded 90% at the last stage. This study contributes new insights into the effective utilization of bioactive ingredients in noni fruit.PMID:38631202 | DOI:10.1016/j.foodchem.2024.139357

Modulation of gut microbiota and metabolites by Flammulina velutipes polysaccharides during in vitro human fecal fermentation: Unveiling Bacteroides as a potential primary degrader

Wed, 17/04/2024 - 12:00
Food Chem. 2024 Apr 10;450:139309. doi: 10.1016/j.foodchem.2024.139309. Online ahead of print.ABSTRACTFlammulina velutipes, a widely cultivated species of edible fungus, exhibits diverse functional activities attributed to its polysaccharides. In this study, we employed an in vitro model to investigate the impact of F. velutipes polysaccharides (FVP) fermentation on gut microbiota, with a particular focus on Bacteroides. FVP fermentation resulted in the proliferation of microbiota associated with short-chain fatty acid (SCFA) metabolism and suppression of Escherichia-Shigella. Bacteroides emerged as potential primary degraders of FVP, with species-level analysis identifying the preference of B. thetaiotaomicron and B. intestinalis in FVP degradation. Metabolomics analysis revealed significant increases in hypoxanthine and 7-methyladenine contents, with histidine metabolism emerging as the most enriched pathway. B. nordii and B. xylanisolvens exhibited the most influence on amino acid and SCFA metabolism. Understanding the mechanisms by which gut microbiota metabolize FVP can provide valuable insights into the potential of FVP to promote intestinal health and disease prevention.PMID:38631200 | DOI:10.1016/j.foodchem.2024.139309

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