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

Bayesian Simultaneous Factorization and Prediction Using Multi-Omic Data

Mon, 01/07/2024 - 12:00
Comput Stat Data Anal. 2024 Sep;197:107974. doi: 10.1016/j.csda.2024.107974. Epub 2024 Apr 30.ABSTRACTIntegrative factorization methods for multi-omic data estimate factors explaining biological variation. Factors can be treated as covariates to predict an outcome and the factorization can be used to impute missing values. However, no available methods provide a comprehensive framework for statistical inference and uncertainty quantification for these tasks. A novel framework, Bayesian Simultaneous Factorization (BSF), is proposed to decompose multi-omics variation into joint and individual structures simultaneously within a probabilistic framework. BSF uses conjugate normal priors and the posterior mode of this model can be estimated by solving a structured nuclear norm-penalized objective that also achieves rank selection and motivates the choice of hyperparameters. BSF is then extended to simultaneously predict a continuous or binary phenotype while estimating latent factors, termed Bayesian Simultaneous Factorization and Prediction (BSFP). BSF and BSFP accommodate concurrent imputation, i.e., imputation during the model-fitting process, and full posterior inference for missing data, including "blockwise" missingness. It is shown via simulation that BSFP is competitive in recovering latent variation structure, and demonstrate the importance of accounting for uncertainty in the estimated factorization within the predictive model. The imputation performance of BSF is examined via simulation under missing-at-random and missing-not-at-random assumptions. Finally, BSFP is used to predict lung function based on the bronchoalveolar lavage metabolome and proteome from a study of HIV-associated obstructive lung disease, revealing multi-omic patterns related to lung function decline and a cluster of patients with obstructive lung disease driven by shared metabolomic and proteomic abundance patterns.PMID:38947282 | PMC:PMC11210674 | DOI:10.1016/j.csda.2024.107974

Alzheimer's disease CSF biomarkers correlate with early pathology and alterations in neuronal and glial gene expression

Mon, 01/07/2024 - 12:00
medRxiv [Preprint]. 2024 Jun 13:2024.06.11.24308706. doi: 10.1101/2024.06.11.24308706.ABSTRACTINTRODUCTION: Normal pressure hydrocephalus (NPH) patients undergoing cortical shunting frequently show early AD pathology on cortical biopsy, which is predictive of progression to clinical AD. The objective of this study was to use samples from this cohort to identify CSF biomarkers for AD-related CNS pathophysiologic changes using tissue and fluids with early pathology, free of post-mortem artifact.METHODS: We analyzed Simoa, proteomic, and metabolomic CSF data from 81 patients with previously documented pathologic and transcriptomic changes.RESULTS: AD pathology on biopsy correlates with CSF β-amyloid-40/42, neurofilament light chain (NfL), and phospho-tau-181(p-tau181)/β-amyloid-42, while several gene expression modules correlate with NfL. Proteomic analysis highlights 7 core proteins that correlate with pathology and gene expression changes on biopsy, and metabolomic analysis of CSF identifies disease-relevant groups that correlate with biopsy data..DISCUSSION: As additional biomarkers are added to AD diagnostic panels, our work provides insight into the CNS pathophysiology these markers are tracking.PMID:38947015 | PMC:PMC11213077 | DOI:10.1101/2024.06.11.24308706

Receptor and metabolic insights on the ability of caffeine to prevent alcohol-induced stimulation of mesolimbic dopamine transmission

Mon, 01/07/2024 - 12:00
Res Sq [Preprint]. 2024 Jun 11:rs.3.rs-4289552. doi: 10.21203/rs.3.rs-4289552/v1.ABSTRACTThe consumption of alcohol and caffeine affects the lives of billions of individuals worldwide. Although recent evidence indicates that caffeine impairs the reinforcing properties of alcohol, a characterization of its effects on alcohol-stimulated mesolimbic dopamine (DA) function was lacking. Acting as the pro-drug of salsolinol, alcohol excites DA neurons in the posterior ventral tegmental area (pVTA) and increases DA release in the nucleus accumbens shell (AcbSh). Here we show that caffeine, via antagonistic activity on A2A adenosine receptors (A2AR), prevents alcohol-dependent activation of mesolimbic DA function as assessed, in-vivo, by brain microdialysis of AcbSh DA and, in-vitro, by electrophysiological recordings of pVTA DA neuronal firing. Accordingly, while the A1R antagonist DPCPX fails to prevent the effects of alcohol on DA function, both caffeine and the A2AR antagonist SCH 58261 prevent alcohol-dependent pVTA generation of salsolinol and increase in AcbSh DA in-vivo, as well as alcohol-dependent excitation of pVTA DA neurons in-vitro. However, caffeine also prevents direct salsolinol- and morphine-stimulated DA function, suggesting that it can exert these inhibitory effects also independently from affecting alcohol-induced salsolinol formation or bioavailability. Finally, untargeted metabolomics of the pVTA showcases that caffeine antagonizes alcohol-mediated effects on molecules (e.g. phosphatidylcholines, fatty amides, carnitines) involved in lipid signaling and energy metabolism, which could represent an additional salsolinol-independent mechanism of caffeine in impairing alcohol-mediated stimulation of mesolimbic DA transmission. In conclusion, the outcomes of this study strengthen the potential of caffeine, as well as of A2AR antagonists, for future development of preventive/therapeutic strategies for alcohol use disorder.PMID:38946995 | PMC:PMC11213171 | DOI:10.21203/rs.3.rs-4289552/v1

Genomes and secondary metabolomes of Streptomyces spp. isolated from Leontopodium nivale ssp. alpinum

Mon, 01/07/2024 - 12:00
Front Microbiol. 2024 Jun 14;15:1408479. doi: 10.3389/fmicb.2024.1408479. eCollection 2024.ABSTRACTBacterial endophytes dwelling in medicinal plants represent an as yet underexplored source of bioactive natural products with the potential to be developed into drugs against various human diseases. For the first time, several Streptomyces spp. were isolated from the rare and endangered traditional medicinal plant Leontopodium nivale ssp. alpinum, also known as Edelweiss. In the search for novel natural products, nine endophytic Streptomyces spp. from Edelweiss were investigated via genome sequencing and analysis, followed by fermentation in different media and investigation of secondary metabolomes. A total of 214 secondary metabolite biosynthetic gene clusters (BGCs), of which 35 are presumably unique, were identified by the bioinformatics tool antiSMASH in the genomes of these isolates. LC-MS analyses of the secondary metabolomes of these isolates revealed their potential to produce both known and presumably novel secondary metabolites, whereby most of the identified molecules could be linked to their cognate BGCs. This work sets the stage for further investigation of endophytic streptomycetes from Edelweiss aimed at the discovery and characterization of novel bioactive natural products.PMID:38946903 | PMC:PMC11212599 | DOI:10.3389/fmicb.2024.1408479

Characterization of disease-specific alterations in metabolites and effects of mesenchymal stromal cells on dystrophic muscles

Mon, 01/07/2024 - 12:00
Front Cell Dev Biol. 2024 Jun 14;12:1363541. doi: 10.3389/fcell.2024.1363541. eCollection 2024.ABSTRACTINTRODUCTION: Duchenne muscular dystrophy (DMD) is a genetic disorder caused by mutations in the dystrophin-encoding gene that leads to muscle necrosis and degeneration with chronic inflammation during growth, resulting in progressive generalized weakness of the skeletal and cardiac muscles. We previously demonstrated the therapeutic effects of systemic administration of dental pulp mesenchymal stromal cells (DPSCs) in a DMD animal model. We showed preservation of long-term muscle function and slowing of disease progression. However, little is known regarding the effects of cell therapy on the metabolic abnormalities in DMD. Therefore, here, we aimed to investigate the mechanisms underlying the immunosuppressive effects of DPSCs and their influence on DMD metabolism.METHODS: A comprehensive metabolomics-based approach was employed, and an ingenuity pathway analysis was performed to identify dystrophy-specific metabolomic impairments in the mdx mice to assess the therapeutic response to our established systemic DPSC-mediated cell therapy approach.RESULTS AND DISCUSSION: We identified DMD-specific impairments in metabolites and their responses to systemic DPSC treatment. Our results demonstrate the feasibility of the metabolomics-based approach and provide insights into the therapeutic effects of DPSCs in DMD. Our findings could help to identify molecular marker targets for therapeutic intervention and predict long-term therapeutic efficacy.PMID:38946797 | PMC:PMC11211584 | DOI:10.3389/fcell.2024.1363541

Sex Differences in the Blood Metabolome During Acute Response to Ischemic Stroke

Mon, 01/07/2024 - 12:00
J Womens Health (Larchmt). 2024 Jul 1. doi: 10.1089/jwh.2023.1133. Online ahead of print.ABSTRACTIntroduction: Females suffer greater lifetime risk of stroke and greater morbidity and mortality from stroke compared with males. This study's objective was to identify differences in metabolomic profiling of females and males with stroke and which differences were associated with neurological outcome. Methods: Females and males with acute ischemic stroke enrolled in the Emergency Medicine Specimen Bank at a comprehensive stroke center provided whole blood samples upon arrival for mass spectrometry-based metabolomics. We used descriptive statistics to characterize the cohort. A linear regression model was fit for individual metabolites to determine differences in relative abundance between males and females while controlling for covariates (age, race/ethnicity, postmenopausal status, cardiovascular risk factors, depression, time between sample collection and last known well, and initial National Institutes of Health Stroke Scale [NIHSS] score). For each differentially expressed metabolite, a linear regression model was fit to determine the association between the metabolite and NIHSS at 24 hours after admission while controlling for the covariates and acute treatments. Results: After adjusting for covariates, eight metabolites differed in females and males with a stroke. These included amino acids or their metabolites (proline and tryptophan), nucleotides (guanosine diphosphate [GDP], and inosine-3',5'-cyclic monophosphate), citrate, dehydroascorbate, choline, and acylcarnitine-(5-OH). GDP and dehydroascorbate were significantly associated with 24-hour NIHSS (p = 0.0991). Conclusions: Few metabolites were differentially abundant in blood after a stroke when comparing females with males and controlling for confounders, but the interactions between biological sex and GDP, as well as biological sex and dehydroascorbate, were associated with 24-hour neurological function. This has important implications for future studies that evaluate the therapeutic potential of these metabolites in ischemic stroke.PMID:38946610 | DOI:10.1089/jwh.2023.1133

Metabolomics analyses reveal the crucial role of ERK in regulating metabolic pathways associated with the proliferation of human cutaneous T-cell lymphoma cells treated with Glabridin

Mon, 01/07/2024 - 12:00
Cell Prolif. 2024 Jun 30:e13701. doi: 10.1111/cpr.13701. Online ahead of print.ABSTRACTCutaneous T-cell lymphomas (CTC) are a heterogeneous group of T-cell lymphoproliferative malignancies of the skin with limited treatment options, increased resistance and remission. Metabolic reprogramming is vital in orchestrating the uncontrolled growth and proliferation of cancer cells. Importantly, deregulated signalling plays a significant role in metabolic reprogramming. Considering the crucial role of metabolic reprogramming in cancer-cell growth and proliferation, target identification and the development of novel and multi-targeting agents are imperative. The present study explores the underlying mechanisms and metabolic signalling pathways associated with Glabridin mediated anti-cancer actions in CTCL. Our results show that Glabridin significantly inhibits the growth of CTCL cells through induction of programmed cell death (PCD) such as apoptosis, autophagy and necrosis. Interestingly, results further show that Glabridin induces PCD in CTCL cells by targeting MAPK signalling pathways, particularly the activation of ERK. Further, Glabridin also sensitized CTCL cells to the anti-cancer drug, bortezomib. Importantly, LC-MS-based metabolomics analyses further showed that Glabridin targeted multiple metabolites and metabolic pathways intricately involved in cancer cell growth and proliferation in an ERK-dependent fashion. Overall, our findings revealed that Glabridin induces PCD and attenuates the expression of regulatory proteins and metabolites involved in orchestrating the uncontrolled proliferation of CTCL cells through ERK activation. Therefore, Glabridin possesses important features of an ideal anti-cancer agent.PMID:38946222 | DOI:10.1111/cpr.13701

An insight into trichomes-deficiency and trichomes-rich black teas by comparative metabolomics: The impact of oxidized trichomes on metabolic profiles and infusion color

Sun, 30/06/2024 - 12:00
Food Res Int. 2024 Aug;190:114638. doi: 10.1016/j.foodres.2024.114638. Epub 2024 Jun 13.ABSTRACTTea trichomes were regarded as an essential evaluation index for reflecting tea flavor quality in terms of aroma and influence on infusion color. This study reveals the impact of golden oxidized trichomes on the color, volatile and non-volatile metabolites of black teas through comparative metabolomics combined quantitative analysis on hongbiluo (trichomes-deficiency black teas), hongjinluo (trichomes-rich black teas), and trichomes (from hongjinluo). Forty-six volatile components were detected using headspace solid-phase microextraction gas chromatography-mass spectrometry, while the results suggested that the contribution of trichomes to black teas is limited. A total of 60 marker non-volatile compounds were identified, including catechins, catechin oxidation products, flavonoid glycosides, organic acids, hydrolysable tannins and amino acids. Notably, p-coumaroyl-kaempferol glucosides, and catechin dimers demonstrated high levels in independent trichomes and showed a positive correlation with the brightness and yellow hue of black tea infusions, specifically kaempferol 3-O-di-(p-coumaroyl)-hexoside. Furthermore, results from fractional extraction analysis of separated trichomes provided that N-ethyl-2-pyrrolidinone-substituted epicatechin gallates, acylated kaempferol glycosides, and chromogenic catechins dimers, such as theaflavins, were primary color contributors in oxidized trichomes. Especially, we found that epicatechin gallate (ECG) and its derivates, 3'-O-methyl-ECG and N-ethyl-2-pyrrolidinone-substituted ECG, highly accumulated in trichomes, which may be associated with the varieties of hongbiluo and hongjinluo black teas. Eventually, addition tests were applied to verify the color contribution of trichome mixtures. Our findings employed comprehensive information revealing that golden oxidized trichomes contributed significantly to the brightness and yellow hue of black tea infusion, but their contribution to the aroma and metabolic profile is limited. These findings may contribute to the effective modulation of the infusion color during black tea production by regulating the proportion of tea trichomes or screening trichomes-rich or deficiency varieties.PMID:38945627 | DOI:10.1016/j.foodres.2024.114638

The effect of different drying temperatures on flavonoid glycosides in white tea: A targeted metabolomics, molecular docking, and simulated reaction study

Sun, 30/06/2024 - 12:00
Food Res Int. 2024 Aug;190:114634. doi: 10.1016/j.foodres.2024.114634. Epub 2024 Jun 10.ABSTRACTDrying is an important stage used to improve the quality of white tea (WT). However, the effect of the drying temperature on the key taste compounds in WT remains unclear. In this study, targeted metabolomics, molecular docking, and a simulated reaction were used to investigate the transformation mechanism of flavonoid glycosides (FGs) in WT during drying at 60, 80, and 100 °C and its impact on taste. There were 45 differential FGs in WT at three drying temperatures. Compared with the withering samples for 48 h, the total FGs contents at three drying temperatures showed a decreasing trend, with quercetin-3-O-galactoside and kaempferol-3-O-glucoside showing the most degradation. These results were confirmed via a simulated drying reaction of FGs standards. Drying at 80 and 100 °C contributed to the formation of flavonoid-C-glycosides, but only trace amounts of these compounds were observed. In addition, nine key taste FGs were selected using dose-over-threshold values. These FGs regulated the taste of WT, mainly by binding to taste receptors via hydrogen bond, hydrophobic and electrostatic interactions. Finally, the taste acceptability of WT dried at 60 °C was found to be the highest, as this method could properly reduce the contents of FGs, weaken the bitterness and astringency, and retain the sweet and umami taste. This study revealed for the first time the transformation mechanism of sensory-active FGs affected by drying temperature, which provides a novel perspective for the analysis of the formation mechanism of the unique flavor of WT and the optimization of this process.PMID:38945623 | DOI:10.1016/j.foodres.2024.114634

Dietary intake of a MFGM/EV-rich concentrate promotes accretion of very long odd-chain sphingolipids and increases lipid metabolic turnover at the whole-body level

Sun, 30/06/2024 - 12:00
Food Res Int. 2024 Aug;190:114601. doi: 10.1016/j.foodres.2024.114601. Epub 2024 Jun 4.ABSTRACTLipids from cow milk fat globule membranes (MFGMs) and extracellular vesicles (EVs) are considered beneficial for neurodevelopment, cognitive maintenance and human health in general. Nevertheless, it is largely unknown whether intake of infant formulas and medical nutrition products rich in these particles promote accretion of specific lipids and whether this affects metabolic homeostasis. To address this, we carried out a 16-week dietary intervention study where mice were supplemented with a MFGM/EV-rich concentrate, a control diet supplemented with a whey protein concentrate and devoid of milk lipids, or regular chow. Assessment of commonly used markers of metabolic health, including body weight, glucose intolerance and liver microanatomy, demonstrated no differences across the dietary regimes. In contrast, in-depth lipidomic analysis revealed accretion of milk-derived very long odd-chain sphingomyelins and ceramides in blood plasma and multiple tissues of mice fed the MFGM/EV diet. Furthermore, lipidomic flux analysis uncovered that mice fed the MFGM/EV diet have increased lipid metabolic turnover at the whole-body level. These findings help fill a long-lasting knowledge gap between the intake of MFGM/EV-containing foods and the health-promoting effects of their lipid constituents. In addition, the findings suggest that dietary sphingomyelins or ceramide-breakdown products with very long-chains can be used as structural components of cellular membranes, lipoprotein particles and signaling molecules that modulate metabolic homeostasis and health.PMID:38945615 | DOI:10.1016/j.foodres.2024.114601

Effect of radio frequency roasting on the lipid profile of peanut oil and the mechanism of lipids transformation: Revealed by untargeted lipidomics approach

Sun, 30/06/2024 - 12:00
Food Res Int. 2024 Aug;190:114592. doi: 10.1016/j.foodres.2024.114592. Epub 2024 Jun 2.ABSTRACTRadio frequency (RF) heating has been proved an alternative roasting method for peanuts, which could effectively degrade aflatoxins and possesses the advantages of greater heating efficiency and penetration depth. This study aimed to investigate the influences of RF roasting on the lipid profile of peanut oil under 150 °C target temperature with varied peanut moisture contents (8.29 % and 20 %) and holding times (0, 7.5, and 15 min), using ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS)-based lipidomics. In total, 2587 lipid species from 35 subclasses were identified. After roasting, the contents of sterol lipid (ST) and subclasses of glycerophospholipids (GPs) and glycoglycerolipids increased significantly, while fatty acid (FA), Oxidized (Ox-) FA, cholesterol (CE), and all subclasses of glycerolipids (GLs) decreased, and 1084 differential lipids were screened. The highest ST and lowest CE contents in peanut oil were achieved by medium roasting (7.5 min). The raise in moisture content of peanut simply affected a few GPs subclasses adversely. Compared with hot air (HA) roasting, RF decelerated lipid oxidation, showing higher levels of diacylglycerol, triacylglycerol and FA, with no additional negative impact and only 69 exclusive differential lipids. During RF roasting, hydrolysis and oxidation of fatty acyl chains into secondary oxides were the central behaviors of lipids transformation. This study could provide insights into the lipid changes and transformation mechanism of peanut oil by RF roasting processing.PMID:38945611 | DOI:10.1016/j.foodres.2024.114592

Polystyrene microplastics exposure reduces meat quality and disturbs skeletal muscle angiogenesis via thrombospondin 1

Sun, 30/06/2024 - 12:00
Food Res Int. 2024 Aug;190:114581. doi: 10.1016/j.foodres.2024.114581. Epub 2024 Jun 1.ABSTRACTMicroplastics (MPs) pose a significant threat to livestock health. Yet, the roles of polystyrene MPs (PS-MPs) on meat quality and skeletal muscle development in pigs have not been fully determined. To investigate the effect of PS-MPs on skeletal muscle, piglets were given diets supplementation with 0 mg/kg (CON group), 75 mg/kg (75 mg/kg PS-MPs group), and 150 mg/kg PS-MPs (150 mg/kg PS-MPs group), respectively. The results indicated that the average daily gain (ADG) of piglets in the 150 mg/kg PS-MPs group was significantly lower than that in the CON group. No significant differences were observed in the final body weight and ADG between the CON group and the 75 mg/kg PS-MPs group. Piglets in the 150 mg/kg PS-MPs group exhibited decreased meat redness index and type I muscle fiber density. Metabolomic analysis revealed that the contents of meat flavor compounds carnosine, beta-alanine, palmitic acid, and niacinamide in muscle were lower in the 150 mg/kg PS-MPs group than in the CON group. Additionally, piglets subjected to 150 mg/kg PS-MPs exhibited impaired muscle angiogenesis. Further analysis indicated that PS-MPs exposure up-regulated thrombospondin 1 (THBS1) expression by inhibiting THBS1 mRNA and protein degradation, thereby disrupting skeletal muscle angiogenesis. These findings indicate that PS-MPs exposure adversely affects meat quality and hinders skeletal muscle angiogenesis in pigs, providing deeper insights into the detrimental effects of PS-MPs on meat quality and skeletal muscle development.PMID:38945601 | DOI:10.1016/j.foodres.2024.114581

Unveiling the synthesis of aromatic compounds in sauce-flavor Daqu from the functional microorganisms to enzymes

Sun, 30/06/2024 - 12:00
Food Res Int. 2024 Aug;190:114628. doi: 10.1016/j.foodres.2024.114628. Epub 2024 Jun 13.ABSTRACTAromatic compounds serve as the primary source of floral and fruity aromas in sauce-flavor (Maotai flavor) baijiu, constituting the skeleton components of its flavor profile. Nevertheless, the formation mechanism of these compounds and key aroma-producing enzymes in sauce-flavor Daqu (fermentation agent, SFD) remain elusive. Here, we combined metagenomics, metaproteomics, metabolomics, and key enzyme activity to verify the biosynthesis pathway of aromatic compounds and to identify key enzymes, genes, and characteristic microorganisms in SFD. The results showed that the later period of fermentation was critical for the generation of aromatic compounds in SFD. In-situ verification was conducted on the potential key enzymes and profiles in various metabolites, providing comprehensive evidence for the main synthetic pathways of aromatic compounds in SFD. Notably, our results showed that primary amine oxidase (PrAO) and aldehyde dehydrogenase (ALDH) emerged as two key enzymes promoting aromatic compound synthesis. Additionally, two potential key functional genes regulating aromatics generation were identified during SFD fermentation through correlation analysis between proteins and relevant metabolites, coupled with in vitro amplification test. Furthermore, original functional strains (Aspergillus flavus-C10 and Aspergillus niger-IN2) exhibiting high PrAO and ALDH production were successfully isolated from SFD, thus validating the results of metagenomics and metaproteomics analyses. This study comprehensively elucidates the pathway of aromatic compound formation in SFD at the genetic, proteomic, enzymatic, and metabolomic levels, providing new ideas for the investigation of key flavor substances in baijiu. Additionally, these findings offer valuable insights into the regulatory mechanisms of aromatic compounds generation.PMID:38945581 | DOI:10.1016/j.foodres.2024.114628

Metabolomics comparison of four varieties apple with different browning characters in response to pretreatment during pulp processing

Sun, 30/06/2024 - 12:00
Food Res Int. 2024 Aug;190:114600. doi: 10.1016/j.foodres.2024.114600. Epub 2024 Jun 6.ABSTRACTBrowning commonly appeared in apple processing, which varied in different apple varieties. Present work investigated the metabolomics of four varieties apple of Yataka, Gala, Sansa, and Fuji, which possessed different browning characteristics and related enzymes. Sansa as browning insensitive apple variety, exhibited the least chroma change with the lowest PPO activity and the highest SOD activity among the four apple varieties. Browning inhibition pretreatment increased the activity of SOD and PAL and decreased PPO and POD activity. In addition, metabolomic variances among the four apple varieties (FC), their browning pulp (BR) and browning inhibition pulp (CM) were compared. And the key metabolites were in-depth analyzed to match the relevant KEGG pathways and speculated metabolic networks. There were 487, 644, and 494 significant differential metabolites detected in FC, BR and CM, which were consisted of lipids, benzenoids, phenylpropanoids, organheterocyclic compounds, organic acids, nucleosides, accounting for 23 %, 11 %, 15 %, 16 %, 11 % of the total metabolites. The differential metabolites were matched with 39, 49, and 36 KEGG pathways in FC, BR, and CM, respectively, in which other secondary metabolites biosynthesis metabolism was the most significant in FC, lipid metabolism was the most significant in BR and CM, and energy metabolism was markedly annotated in CM. Notably, Sansa displayed the highest number of differential metabolites in both its BR (484) and CM (342). The BR of Sansa was characterized by flavonoid biosynthesis, while the other three apple varieties were associated with α-linolenic acid metabolism. Furthermore, in browning sensitive apple varieties, the flavonoid and phenylpropanoid biosynthesis pathway was significantly activated by browning inhibition pretreatment. Phenolic compounds, lipids, sugars, organic acids, nucleotides, and adenosine were regulated differently in the four apple varieties, potentially serving as key regulatory sites. Overall, this work provides novel insight for browning prevention in different apple varieties.PMID:38945570 | DOI:10.1016/j.foodres.2024.114600

Aloe vera and tea polyphenols composite coating delays passion fruit senescence by promoting phenolic and flavonoid accumulation

Sun, 30/06/2024 - 12:00
Food Res Int. 2024 Aug;190:114594. doi: 10.1016/j.foodres.2024.114594. Epub 2024 Jun 5.ABSTRACTPassion fruits are highly perishable during postharvest storage and transportation, prompting the exploration of natural preservatives. This study investigates the synergistic effects of Aloe vera (ALV) and tea polyphenols (TP) coatings on quality retention, ripening modulation, and associated regulatory mechanisms in stored "golden" passion fruit (Passiflora spp.) at 10 °C. The application of a composite coating comprising 40 % ALV and 0.1 g/L TP led to notable improvements in fruit preservation over a 28-day storage period. At the day of 28, quantitatively, the ALV + TP treatment reduced weight loss by 41.60 %, shrinkage index by 28.13 %, and decay index by 50 %, significantly outperforming the control and individual treatments; the treated fruits exhibited enhanced firmness, reduced ethylene production, and the respiration peak was delayed about 6 days. Metabolomic analysis revealed pronounced alterations in key metabolic pathways, notably phenylpropanoid and flavonoid biosynthesis. Specifically, significant increases in metabolites such as phenolic acids (Feruloylmalic acid and Acropyrone) and flavonoids (Okanin-4'-O-glucoside, Apigenin-8-C-Arabinoside, Quercetin-3-O- (2'-O-galloyl) galactoside, and Catechin callate) were observed. Concurrently, transcript levels of key biosynthetic genes including cinnamate 4-hydroxylase (PeC4H), 4-coumarate-coenzyme a ligase (PeC4L), hydroxycinnamoyl transferase (PeHCT) and flavonol synthase (PeFLS) were significantly up-regulated by ALV + TP coating, indicating a robust activation of these pathways. The findings underscore the effectiveness of the ALV + TP composite coating as an environmentally friendly strategy for enhancing postharvest quality by promoting the accumulation of beneficial phenolic acids and flavonoids in passion fruits.PMID:38945568 | DOI:10.1016/j.foodres.2024.114594

Seasonal dynamics of the microbiota and nutritional composition in bee bread from Apis cerana and Apis mellifera colonies

Sun, 30/06/2024 - 12:00
Food Res Int. 2024 Aug;190:113905. doi: 10.1016/j.foodres.2023.113905. Epub 2023 Dec 27.ABSTRACTBee bread is a product of honeybees, which collect and ferment pollen, that contains highly nutritious and easily digestible active substances. However, its nutritional composition varies significantly with fermentation strains and seasonal changes. To unveil the patterns of microbial community and nutritional component changes in bee bread across seasons, we employed high-throughput techniques to assess the diversity of bacteria and fungi in bee bread. The results indicated that the compositions of bacteria and fungi in bee bread undergo significant seasonal variation, with noticeable changes in the microbial diversity of bee bread from different bee species. Subsequently, metabolomic analysis revealed high activity of glycerophospholipid metabolism in bee bread. Furthermore, our analysis identifaied noteworthy differences in nutritional components, including pH values, sugar content, and free amino acid levels, in bee bread across different seasons.PMID:38945555 | DOI:10.1016/j.foodres.2023.113905

Phototherapy Alters the Plasma Metabolite Profile in Infants Born Preterm with Hyperbilirubinemia

Sun, 30/06/2024 - 12:00
J Pediatr. 2024 Jun 28:114175. doi: 10.1016/j.jpeds.2024.114175. Online ahead of print.ABSTRACTOBJECTIVE: To investigate the effects of gestational age (GA) and phototherapy on the plasma metabolite profile of preterm infants with neonatal hyperbilirubinemia (NHB).STUDY DESIGN: From a cohort of prospectively enrolled infants born preterm (N=92), plasma samples of very preterm (VPT; GA, 28+0 to 31+6 weeks, N =27) and moderate/late preterm (M/LPT; GA, 32+0 to 35+6 weeks, N =33) infants requiring phototherapy for NHB were collected prior to the initiation of phototherapy and 24 hours after starting phototherapy. An additional sample was collected 48 hours after starting phototherapy in a randomly selected subset (N=30; VPT N=15; M/LPT N=15). Metabolite profiles were determined using ultraperformance liquid chromatography tandem mass spectroscopy. Two-way ANCOVA was used to identify metabolites that differed between GA groups and timepoints after adjusting for total serum bilirubin (TSB) levels (FDR q-value<0.05). Top impacted pathways were identified using pathway over-representation analysis.RESULTS: Phototherapy was initiated at lower TSB (mean ± SD mg/dL) levels in VPT compared with M/LPT infants (7.3 ± 1.4 vs. 9.9 ± 1.9, p<0.01). We identified 664 metabolites that were significant for a phototherapy effect, 191 metabolites significant for GA, and 46 metabolites significant for GA x phototherapy interaction (FDR q-value<0.05). Longer duration phototherapy had a larger mean effect size (24 hours post-phototherapy: d=0.36; 48 hours post-phototherapy: d=0.43). Top pathways affected by phototherapy included membrane lipid metabolism, one-carbon metabolism, creatine biosynthesis, and oligodendrocyte differentiation.CONCLUSION: Phototherapy alters the plasma metabolite profile more than GA in preterm infants with NHB, affecting pathways related to lipid and one-carbon metabolism, energy biosynthesis, and oligodendrocyte differentiation.PMID:38945444 | DOI:10.1016/j.jpeds.2024.114175

The mechanism by which oriented polypropylene packaging alleviates postharvest 'Black Spot' in radish root (Raphanus sativus)

Sun, 30/06/2024 - 12:00
J Adv Res. 2024 Jun 28:S2090-1232(24)00263-7. doi: 10.1016/j.jare.2024.06.026. Online ahead of print.ABSTRACTINTRODUCTION: The postharvest physiological disorder known as 'black spot' in radish roots (Raphanus sativus) poses a significant challenge to quality maintenance during storage, particularly under summer conditions. The cause of this disorder, however, is poorly understood.OBJECTIVES: Characterize the underlying causes of 'black spot' disorder in radish roots and identify strategies to delay its onset.METHODS: Radish roots were placed in either polyvinyl chloride (PVC) or oriented polypropylene (OPP) packaging and stored for 4 days at 30 ℃. Appearance and physiological parameters were assessed and transcriptomic and metabolomic analyses were conducted to identify the key molecular and biochemical factors contributing to the disorder and strategies for delaying its onset and development.RESULTS: OPP packaging effectively delayed the onset of 'black spot' in radishes, potentially due to changes in phenolic and lipid metabolism. Regarding phenolic metabolism, POD and PPO activity decreased, RsCCR and RsPOD expression was downregulated, genes involved in phenols and flavonoids synthesis were upregulated and their content increased, preventing the oxidative browning of phenols and generally enhancing stress tolerance. Regarding lipid metabolism, the level of alpha-linolenic acid increased, and genes regulating cutin and wax synthesis were upregulated. Notably, high flavonoid and low ROS levels collectively inhibited RsPLA2G expression, which reduced the production of arachidonic acid, pro-inflammatory compounds (LTA4 and PGG2), and ROS, alleviating the inflammatory response and oxidative stress in radish epidermal tissues.CONCLUSION: PVC packaging enhanced the postharvest onset of 'black spot' in radishes, while OPP packaging delayed both its onset and development. Our study provides insights into the response of radishes to different packaging materials during storage, and the causes and host responses that either enhance or delay 'black spot' disorder onset. Further studies will be conducted to confirm the molecular and biochemical processes responsible for the onset and development of 'black spot' in radishes.PMID:38945295 | DOI:10.1016/j.jare.2024.06.026

Metabolites of blueberry roots at different developmental stages strongly shape microbial community structure and intra-kingdom interactions at the root-soil interface

Sun, 30/06/2024 - 12:00
Sci Total Environ. 2024 Jun 28:174333. doi: 10.1016/j.scitotenv.2024.174333. Online ahead of print.ABSTRACTThe rhizosphere microorganisms of blueberry plants have long coexisted with their hosts under distinctively acidic soil conditions, exerting a profound influence on host performance through mutualistic symbiotic interactions. Meanwhile, plants can regulate rhizosphere microorganisms by exerting host effects to meet the functional requirements of plant growth and development. However, it remains unknown how the developmental stages of blueberry plants affect the structure, function, and interactions of the rhizosphere microbial communities. Here, we examined bacterial communities and root metabolites at three developmental stages (flower and leaf bud development stage, fruit growth and development stage, and fruit maturation stage) of blueberry plants. The results revealed that the Shannon and Chao 1 indices as well as community composition varied significantly across all three developmental stages. The relative abundance of Actinobacteria significantly increased by 10 % (p < 0.05) from stage 1 to stage 2, whereas that of Proteobacteria decreased significantly. The co-occurrence network analysis revealed a relatively complex network with 1179 edges and 365 nodes in the stage 2. Niche breadth was highest at stage 2, while niche overlap tended to increase as the plant developed. Furthermore, the untargeted metabolome analysis revealed that the number of differential metabolites of vitamins, nucleic acids, steroids, and lipids increased between stage 1 to stage2 and stage 2 to stage 3, while those for differential metabolites of carbohydrates and peptides decreased. Significant changes in expression levels of levan, L-glutamic acid, indoleacrylic acid, oleoside 11-methyl ester, threo-syringoylglycerol, gingerglycolipid B, and bovinic acid were highly correlated with the bacterial community structure. Collectively, our study reveals that significant alterations in dominant bacterial taxa are strongly correlated with the dynamics of root metabolites. These findings lay the groundwork for developing prebiotic products to enhance the beneficial effects of root microorganisms and boosting blueberry productivity via a sustainable approach.PMID:38945231 | DOI:10.1016/j.scitotenv.2024.174333

Adverse impact of phthalate and polycyclic aromatic hydrocarbon mixtures on birth outcomes: a metabolome Exposome-Wide Association Study

Sun, 30/06/2024 - 12:00
Environ Pollut. 2024 Jun 28:124460. doi: 10.1016/j.envpol.2024.124460. Online ahead of print.ABSTRACTIt has been well-investigating that individual phthalates (PAEs) or polycyclic aromatic hydrocarbons (PAHs) affect public health. However, there is still a gap that the mixture of PAEs and PAHs impacts birth outcomes. Through innovative methods for mixtures in epidemiology, we used a metabolome Exposome-Wide Association Study (mExWAS) to evaluate and explain the association between exposure to PAEs and PAHs mixtures and birth outcomes. Exposure to a higher level of PAEs and PAHs mixture was associated with lower birth weight (maximum cumulative effect: -143.5 g) rather than gestational age. Mono(2-ethlyhexyl) phthalate (MEHP) (posterior inclusion probability, PIP =0.51), 9-hydroxyphenanthrene (9-OHPHE) (PIP =0.53), and 1-hydroxypyrene (1-OHPYR) (PIP =0.28) were identified as the most important compounds in the mixture. In mExWAS, we successfully annotated four overlapping metabolites associated with both MEHP/9-OHPHE/1-OHPYR and birth weight, including arginine, stearamide, Arg-Gln, and valine. Moreover, several lipid-related metabolism pathways, including fatty acid biosynthesis and degradation, alpha-linolenic acid, and linoleic acid metabolism, were disturbed. In summary, these findings may provide new insights into the underlying mechanisms by which PAE and PAHs affect fetal growth.PMID:38945193 | DOI:10.1016/j.envpol.2024.124460

Pages