PubMed

PLoS One. 2023 Aug 8;18(8):e0285401. doi: 10.1371/journal.pone.0285401. eCollection 2023.ABSTRACTAlpinia oxyphylla Fructus, called Yizhi in Chinese, is the dried fruit of Alpinia oxyphylla Miquel. It has been used in traditional Chinese medicine to treat dementia and memory defects of Alzheimer's disease for many years. However, the underlying mechanism is still unclear. In this study, we used a rat Alzheimer's disease model on intrahippocampal injection of aggregated Aβ1-42 to study the effects of Alpinia oxyphylla Fructus. A brain and plasma dual-channel metabolomics approach combined with multivariate statistical analysis was further performed to determine the effects of Alpinia oxyphylla Fructus on Alzheimer's disease animals. As a result, in the Morris water maze test, Alpinia oxyphylla Fructus had a clear ability to ameliorate the impaired learning and memory of Alzheimer's disease rats. 11 differential biomarkers were detected in AD rats' brains. The compounds mainly included amino acids and phospholipids; after Alpinia oxyphylla Fructus administration, 9 regulated biomarkers were detected compared with the AD model group. In the plasma of AD rats, 29 differential biomarkers, primarily amino acids, phospholipids and fatty acids, were identified; After administration, 23 regulated biomarkers were detected. The metabolic pathways of regulated metabolites suggest that Alpinia oxyphylla Fructus ameliorates memory and learning deficits in AD rats principally by regulating amino acid metabolism, lipids metabolism, and energy metabolism. In conclusion, our results confirm and enhance our current understanding of the therapeutic effects of Alpinia oxyphylla Fructus on Alzheimer's disease. Meanwhile, our work provides new insight into the potential intervention mechanism of Alpinia oxyphylla Fructus for Alzheimer's disease treatment.PMID:37552694 | DOI:10.1371/journal.pone.0285401

Metabolomics. 2023 Aug 8;19(8):71. doi: 10.1007/s11306-023-02033-7.ABSTRACTOBJECTIVE: The objective of this study was to investigate the genetic control of polyphenol accumulation in red raspberry (Rubus idaeus L).METHODS: The levels of total anthocyanins and 37 individual polyphenol metabolites were measured over three years in a raspberry biparental mapping population. Quantitative trait loci (QTLs) for these traits were mapped onto a high-density SNP linkage map.RESULTS: At least one QTL was detected for each trait, with good consistency among the years. On four linkage groups (LG), there were major QTLs affecting several metabolites. On LG1, a QTL had large effects on anthocyanins and flavonols containing a rutinoside or rhamnose group. On LG4, a QTL had large effects on several flavonols and on LG5 and LG6 QTLs had large effects on ellagic acid derivatives. Smaller QTLs were found on LG2 and LG3.CONCLUSION: The identification of robust QTLs for key polyphenols in raspberry provides great potential for marker-assisted breeding for improved levels of potentially health beneficial components.PMID:37552331 | DOI:10.1007/s11306-023-02033-7

Blood Adv. 2023 Aug 8:bloodadvances.2023010305. doi: 10.1182/bloodadvances.2023010305. Online ahead of print.ABSTRACTAcquired T-cell dysfunction is common in chronic B-cell malignancies. Given the strong connection between T-cell metabolism and function, we investigated metabolic alterations as the basis for T-cell dysfunction induced by malignant cells. Using B-cell malignant cell lines and human PBMCs, we first established a model which recapitulates major aspects of cancer-induced T-cell dysfunction. Cell lines derived from chronic lymphocytic leukemia (PGA-1, CII, Mec-1), but not from other B-cell malignancies, altered T-cell metabolome by generating a pseudohypoxic state. T cells were retained in aerobic glycolysis and were not able to switch to OXPHOS. Moreover, T cells produced immunosuppressive adenosine that negatively affected function by dampening activation, which could be restored by blocking of adenosine receptors. Subsequently, we uncovered a similar hypoxic-like signature in autologous T cells from primary CLL samples. Pseudohypoxia was reversible upon depletion of CLL cells ex vivo and, importantly, after in vivo reduction of the leukemic burden with combination therapy (Venetoclax and Obinutuzumab), restoring T-cell function. In conclusion, we uncover a pseudohypoxic program connected with T cell dysfunction in CLL. Modulation of hypoxia and the purinergic pathway might contribute to therapeutic restoration of T-cell function.PMID:37552122 | DOI:10.1182/bloodadvances.2023010305

J Neurotrauma. 2023 Aug 8. doi: 10.1089/neu.2023.0046. Online ahead of print.ABSTRACTMild traumatic brain injury (mTBI) accounts for 70% to 90% of all TBI cases. Lipid metabolites have important roles in plasma membrane biogenesis, function, and cell signaling. As TBI can compromise plasma membrane integrity and alter brain cell function, we sought to identify circulating phospholipids alterations after mTBI, and determine if these changes were associated with clinical outcomes. Patients with mTBI (GCS≥13 and loss of consciousness <30 min) were recruited. A total of 84 mTBI subjects were enrolled after admission to a level I trauma center, with the majority having evidence of traumatic intracranial hemorrhage on brain computed tomography (CT). Plasma samples collected within 24 hours of injury with 32 mTBI subjects returning at 3 months after injury for a second plasma sample to be collected. Thirty-five healthy volunteers were enrolled as controls and had a one-time blood draw. Lipid metabolomics was performed on plasma samples from each subject. Fold change of selected lipid metabolites was determined. Multivariable regression models were created to test associations between lipid metabolites and discharge and 6-month Glasgow Outcomes Scale-Extended (GOSE) outcomes [dichotomized between 'good' (GOSE≥7) and 'bad' (GOSE≤6) functional outcomes]. Plasma levels of 31 lipid metabolites were significantly associated with discharge GOSE using univariate models; three of these metabolites were significantly increased, while 14 were significantly decreased in subjects with good outcomes compared to subjects with poor outcomes. In multivariable logistic regression models, higher circulating levels of the lysophospholipids (LPL) 1-linoleoyl-GPC (18:2), 1-linoleoyl-GPE (18:2), and 1-linolenoyl-GPC (18:3) were associated with both good discharge GOSE [OR 12.2 (95%CI 3.35, 58.3), P=5.23x10-4; OR 9.43 (95%CI 2.87, 39.6), P=7.26x10-4; and OR 5.26 (95%CI 1.99, 16.7), P=2.04x10-3, respectively] and 6-month [OR 4.67 (95%CI 1.49, 17.7), P=0.013; OR 2.93 (95%CI 1.11, 8.87), P=0.039; and OR 2.57 (95%CI 1.08, 7.11), P=0.046, respectively]. Compared with healthy volunteers, circulating levels of these three LPLs were decreased early after injury and had normalized by 3-months after injury. Logistic regression models to predict functional outcomes were created by adding each of the above 3 LPLs to a baseline model that included age and sex. Including 1-linoleoyl-GPC (18:2) (8.20% improvement, P=0.009), 1-linoleoyl-GPE (18:2) (8.85% improvement, P=0.021), or 1-linolenoyl-GPC (18:3) (7.68% improvement, P=0.012), significantly improved the area under the curve (AUC) for predicting discharge outcomes compared to the baseline model. Models including 1-linoleoyl-GPC (18:2) significantly improved AUC for predicting 6-month outcomes (9.35% improvement, P=0.034). Models including principal components derived from 25 LPLs significantly improved AUC for prediction of 6-months outcomes (16.0% improvement, P=0.020). Our results demonstrate that higher plasma levels of LPLs (1-linoleoyl-GPC, 1-linoleoyl-GPE, and 1-linolenoyl-GPC) after mTBI are associated with better functional outcomes at discharge and 6 months after injury. This class of phospholipids may represent a potential therapeutic target.PMID:37551969 | DOI:10.1089/neu.2023.0046

ACS Chem Neurosci. 2023 Aug 8. doi: 10.1021/acschemneuro.3c00350. Online ahead of print.ABSTRACTMany mechanisms have been proposed to explain acute antidepressant drug-induced activation of TrkB neurotrophin receptors, but several questions remain. In a series of pharmacological experiments, we observed that TrkB activation induced by antidepressants and several other drugs correlated with sedation, and most importantly, coinciding hypothermia. Untargeted metabolomics of pharmacologically dissimilar TrkB activating treatments revealed effects on shared bioenergetic targets involved in adenosine triphosphate (ATP) breakdown and synthesis, demonstrating a common perturbation in metabolic activity. Both activation of TrkB signaling and hypothermia were recapitulated by administration of inhibitors of glucose and lipid metabolism, supporting a close relationship between metabolic inhibition and neurotrophic signaling. Drug-induced TrkB phosphorylation was independent of electroencephalography slow-wave activity and remained unaltered in knock-in mice with the brain-derived neurotrophic factor (BDNF) Val66Met allele, which have impaired activity-dependent BDNF release, alluding to an activation mechanism independent from BDNF and neuronal activity. Instead, we demonstrated that the active maintenance of body temperature prevents activation of TrkB and other targets associated with antidepressants, including p70S6 kinase downstream of the mammalian target of rapamycin (mTOR) and glycogen synthase kinase 3β (GSK3β). Increased TrkB, GSK3β, and p70S6K phosphorylation was also observed during recovery sleep following sleep deprivation, when a physiological temperature drop is known to occur. Our results suggest that the changes in bioenergetics and thermoregulation are causally connected to TrkB activation and may act as physiological regulators of signaling processes involved in neuronal plasticity.PMID:37551888 | DOI:10.1021/acschemneuro.3c00350

Environ Toxicol. 2023 Aug 8. doi: 10.1002/tox.23926. Online ahead of print.ABSTRACTInflammatory microenvironment may take a promoting role in lung tumorigenesis. However, the molecular characteristics underlying inflammation-related lung cancer remains unknown. In this work, the inflammation-related lung tumorigenesis mouse model was established by treated with B(a)P (1 mg/mouse, once a week for 4 weeks), followed by LPS (2.5 μg/mouse, once every 3 weeks for five times), the mice were sacrificed 30 weeks after exposure. TMT-labeled quantitative proteomics and untargeted metabolomics were used to interrogate differentially expressed proteins and metabolites in different mouse cancer tissues, followed by integrated crosstalk between proteomics and metabolomics through Spearman's correlation analysis. The result showed that compared with the control group, 103 proteins and 37 metabolites in B(a)P/LPS group were identified as significantly altered. By searching KEGG pathway database, proteomics pathways such as Leishmaniasis, Asthma and Intestinal immune network for IgA production, metabolomics pathways such as Vascular smooth muscle contraction, Linoleic acid metabolism and cGMP-PKG signaling pathway were enriched. A total of 22 pathways were enriched after conjoint analysis of the proteomic and metabolomics, and purine metabolism pathway, the unique metabolism-related pathway, which included significantly altered protein (adenylate cyclase 4, ADCY4) and metabolites (L-Glutamine, guanosine monophosphate (GMP), adenosine and guanosine) was found. Results suggested purine metabolism may contribute to the inflammation-related lung tumorigenesis, which may provide novel clues for the therapeutic strategies of inflammation-related lung cancer.PMID:37551664 | DOI:10.1002/tox.23926

J Zhejiang Univ Sci B. 2023 Aug 15;24(8):734-748. doi: 10.1631/jzus.B2200439.ABSTRACTA growing body of evidence has linked the gut microbiota to liver metabolism. The manipulation of intestinal microflora has been considered as a promising avenue to promote liver health. However, the effects of Lactobacillus gasseri LA39, a potential probiotic, on liver metabolism remain unclear. Accumulating studies have investigated the proteomic profile for mining the host biological events affected by microbes, and used the germ-free (GF) mouse model to evaluate host-microbe interaction. Here, we explored the effects of L. gasseri LA39 gavage on the protein expression profiles of the liver of GF mice. Our results showed that a total of 128 proteins were upregulated, whereas a total of 123 proteins were downregulated by treatment with L. gasseri LA39. Further bioinformatics analyses suggested that the primary bile acid (BA) biosynthesis pathway in the liver was activated by L. gasseri LA39. Three differentially expressed proteins (cytochrome P450 family 27 subfamily A member 1 (CYP27A1), cytochrome P450 family 7 subfamily B member 1 (CYP7B1), and cytochrome P450 family 8 subfamily B member 1 (CYP8B1)) involved in the primary BA biosynthesis pathway were further validated by western blot assay. In addition, targeted metabolomic analyses demonstrated that serum and fecal β‍-muricholic acid (a primary BA), dehydrolithocholic acid (a secondary BA), and glycolithocholic acid-3-sulfate (a secondary BA) were significantly increased by L. gasseri LA39. Thus, our data revealed that L. gasseri LA39 activates the hepatic primary BA biosynthesis and promotes the intestinal secondary BA biotransformation. Based on these findings, we suggest that L. gasseri LA39 confers an important function in the gut‒liver axis through regulating BA metabolism.PMID:37551559 | DOI:10.1631/jzus.B2200439

Zool Res. 2023 Sep 18;44(5):894-904. doi: 10.24272/j.issn.2095-8137.2023.084.ABSTRACTConjugative transfer of antibiotic resistance genes (ARGs) by plasmids is an important route for ARG dissemination. An increasing number of antibiotic and nonantibiotic compounds have been reported to aid the spread of ARGs, highlighting potential challenges for controlling this type of horizontal transfer. Development of conjugation inhibitors that block or delay the transfer of ARG-bearing plasmids is a promising strategy to control the propagation of antibiotic resistance. Although such inhibitors are rare, they typically exhibit relatively high toxicity and low efficacy in vivo and their mechanisms of action are inadequately understood. Here, we studied the effects of dihydroartemisinin (DHA), an artemisinin derivative used to treat malaria, on conjugation. DHA inhibited the conjugation of the IncI2 and IncX4 plasmids carrying the mobile colistin resistance gene ( mcr-1) by more than 160-fold in vitro in Escherichia coli, and more than two-fold (IncI2 plasmid) in vivo in a mouse model. It also suppressed the transfer of the IncX3 plasmid carrying the carbapenem resistance gene bla NDM-5 by more than two-fold in vitro. Detection of intracellular adenosine triphosphate (ATP) and proton motive force (PMF), in combination with transcriptomic and metabolomic analyses, revealed that DHA impaired the function of the electron transport chain (ETC) by inhibiting the tricarboxylic acid (TCA) cycle pathway, thereby disrupting PMF and limiting the availability of intracellular ATP for plasmid conjugative transfer. Furthermore, expression levels of genes related to conjugation and pilus generation were significantly down-regulated during DHA exposure, indicating that the transfer apparatus for conjugation may be inhibited. Our findings provide new insights into the control of antibiotic resistance and the potential use of DHA.PMID:37551137 | DOI:10.24272/j.issn.2095-8137.2023.084

Kidney Res Clin Pract. 2023 Jul;42(4):445-459. doi: 10.23876/j.krcp.22.152. Epub 2023 Jul 25.ABSTRACTBACKGROUND: As a leading cause of chronic kidney disease, clinical demand for noninvasive biomarkers of diabetic kidney disease (DKD) beyond proteinuria is increasing. Metabolomics is a popular method to identify mechanisms and biomarkers. We investigated urinary targeted metabolomics in DKD patients.METHODS: We conducted a targeted metabolomics study of 26 urinary metabolites in consecutive patients with DKD stage 1 to 5 (n = 208) and healthy controls (n = 26). The relationships between estimated glomerular filtration rate (eGFR) or urine protein-creatinine ratio (UPCR) and metabolites were evaluated. Multivariate Cox analysis was used to estimate relationships between urinary metabolites and the target outcome, end-stage renal disease (ESRD). C statistics and time-dependent receiver operating characteristics (ROC) were used to assess diagnostic validity.RESULTS: During a median 4.5 years of follow-up, 103 patients (44.0%) progressed to ESRD and 65 (27.8%) died. The median fold changes of nine metabolites belonged to monosaccharide and tricarboxylic acid (TCA) cycle metabolites tended to increase with DKD stage. Myo-inositol, choline, and citrates were correlated with eGFR and choline, while mannose and myo-inositol were correlated with UPCR. Elevated urinary monosaccharide and TCA cycle metabolites showed associations with increased morality and ESRD progression. The predictive power of ESRD progression was high, in the order of choline, myo-inositol, and citrate. Although urinary metabolites alone were less predictive than serum creatinine or UPCR, myo-inositol had additive effect with serum creatinine and UPCR. In time-dependent ROC, myo-inositol was more predictive than UPCR of 1-year ESRD progression prediction.CONCLUSION: Myo-inositol can be used as an additive biomarker of ESRD progression in DKD.PMID:37551126 | DOI:10.23876/j.krcp.22.152

Alzheimers Res Ther. 2023 Aug 7;15(1):134. doi: 10.1186/s13195-023-01278-7.ABSTRACTBACKGROUND: Obstructive sleep apnoea (OSA) has a high prevalence in patients with Alzheimer's disease (AD). Both conditions have been shown to be associated with lipid dysregulation. However, the relationship between OSA severity and alterations in lipid metabolism in the brains of patients with AD has yet to be fully elucidated. In this context, we examined the cerebrospinal fluid (CSF) lipidome of patients with suspected OSA to identify potential diagnostic biomarkers and to provide insights into the pathophysiological mechanisms underlying the effect of OSA on AD.METHODS: The study included 91 consecutive AD patients who underwent overnight polysomnography (PSG) to diagnose severe OSA (apnoea-hypopnea index ≥ 30/h). The next morning, CSF samples were collected and analysed by liquid chromatography coupled to mass spectrometry in an LC-ESI-QTOF-MS/MS platform.RESULTS: The CSF levels of 11 lipid species were significantly different between AD patients with (N = 38) and without (N = 58) severe OSA. Five lipids (including oxidized triglyceride OxTG(57:2) and four unknown lipids) were significantly correlated with specific PSG measures of OSA severity related to sleep fragmentation and hypoxemia. Our analyses revealed a 4-lipid signature (including oxidized ceramide OxCer(40:6) and three unknown lipids) that provided an accuracy of 0.80 (95% CI: 0.71-0.89) in the detection of severe OSA. These lipids increased the discriminative power of the STOP-Bang questionnaire in terms of the area under the curve (AUC) from 0.61 (0.50-0.74) to 0.85 (0.71-0.93).CONCLUSIONS: Our results reveal a CSF lipidomic fingerprint that allows the identification of AD patients with severe OSA. Our findings suggest that an increase in central nervous system lipoxidation may be the principal mechanism underlying the association between OSA and AD.PMID:37550750 | PMC:PMC10408111 | DOI:10.1186/s13195-023-01278-7

Drug Metab Dispos. 2023 Aug 7:DMD-AR-2023-001358. doi: 10.1124/dmd.123.001358. Online ahead of print.ABSTRACTCytochrome P450 2D6 (CYP2D6) is involved in the metabolism of > 20% of marketed drugs. CYP2D6 expression and activity exhibit high interindividual variability and is induced during pregnancy. The farnesoid X receptor (FXR) is a transcriptional regulator of CYP2D6 that is activated by bile acids. In pregnancy, elevated plasma bile acid concentrations are associated with maternal and fetal risks. However, modest changes in bile acid concentrations may occur during healthy pregnancy thereby altering FXR signaling. A previous study demonstrated that hepatic tissue concentrations of bile acids positively correlated with the hepatic mRNA expression of CYP2D6. This study sought to characterize the plasma bile acid metabolome in healthy women (n=47) during mid-pregnancy (25-28 weeks gestation) and {greater than or equal to} 3 months postpartum, and to determine if plasma bile acids correlate with CYP2D6 activity. It is hypothesized that during pregnancy plasma bile acids would favor less hydrophobic bile acids (cholic acid vs. chenodeoxycholic acid), and that plasma concentrations of cholic acid and its conjugates would positively correlate with the urinary ratio of dextrorphan / dextromethorphan. At 25-28 weeks gestation, taurine conjugated bile acids comprised 23% of the quantified serum bile acids compared to 7% {greater than or equal to} 3 months postpartum. Taurocholic acid positively associated with the urinary ratio of dextrorphan / dextromethorphan, a biomarker of CYP2D6 activity. Collectively, these results confirm that the bile acid plasma metabolome differs between pregnancy and postpartum and provide evidence that taurocholic acid may impact CYP2D6 activity during pregnancy. Significance Statement Bile acid homeostasis is altered in pregnancy and plasma concentrations of taurocholic acid positively correlate with CYP2D6 activity. Differences between plasma and/or tissue concentrations of FXR ligands, such as bile acids, may contribute to the high interindividual variability in CYP2D6 expression and activity.PMID:37550070 | DOI:10.1124/dmd.123.001358

J Adv Res. 2023 Aug 5:S2090-1232(23)00207-2. doi: 10.1016/j.jare.2023.08.003. Online ahead of print.ABSTRACTINTRODUCTION: Auricularia auricula is a well-known traditional edible and medical fungus with high nutritional and pharmacological values, as well as metabolic and immunoregulatory properties. Nondigestible fermentable polysaccharides are identified as primary bioactive constituents of Auricularia auricula extracts. However, the exact mechanisms underlying the effects of Auricularia auricula polysaccharides (AAP) on obesity and related metabolic endpoints, including the role of the gut microbiota, remain insufficiently understood.METHODS: The effects of AAP on obesity were assessed within high-fat diet (HFD)-based mice through obesity trait analysis and metabolomic profiling. To determine the mechanistic role of the gut microbiota in observed anti-obesogenic effects AAP, faecal microbiota transplantation (FMT) and pseudo-germ-free mice model treated with antibiotics were also applied, together with 16S rRNA genomic-derived taxonomic profiling.RESULTS: High-fat diet (HFD) murine exposure to AAP thwarted weight gains, reduced fat depositing and enhanced glucose tolerance, together with upregulating thermogenesis proteomic biomarkers within adipose tissue. Serum metabolome indicated these effects were associated with changes in fatty acid metabolism. Intestine-dwelling microbial population assessments discovered that AAP selectively enhanced Papillibacter cinnamivorans, a commensal bacterium with reduced presence in HFD mice. Notably, HFD mice treated with oral formulations of P. cinnamivorans attenuated obesity, which was linked to decreased intestinal lipid transportation and hepatic thermogenesis. Mechanistically, it was demonstrated that P. cinnamivorans regulated intestinal lipids metabolism and liver thermogenesis by reducing the proinflammatory response and gut permeability in a JAK-STAT signaling-related manner.CONCLUSION: Datasets from the present study show that AAP thwarted dietary-driven obesity and metabolism-based disorders by regulating intestinal lipid transportation, a mechanism that is dependent on the gut commensal P. cinnamivorans. These results indicated AAP and P. cinnamivorans as newly identified pre- and probiotics that could serve as novel therapeutics against obesity.PMID:37549868 | DOI:10.1016/j.jare.2023.08.003

Clin Chim Acta. 2023 Aug 5:117507. doi: 10.1016/j.cca.2023.117507. Online ahead of print.ABSTRACTBACKGROUND: Higher levels of physical activity are related to higher 25-(OH)D levels. Total 25-(OH)D (25-(OH)DT) are routinely used in clinical practice to assess vitamin D, however novel biomarkers are currently being investigated as free 25-(OH)D (25-(OH)DF) or vitamin D metabolite ratios (VMRs). The primary aim of our study was to assess 25-(OH)DF, vitamin D metabolites and VMRs in inactive men and athletes. A secondary aim was to check whether regular physical activity influence on vitamin D metabolome. A tertiary aim was to determine the relationship between 25-(OH)DT, 25-(OH)DF, vitamin D binding protein (VDBP), vitamin D metabolites and VMRs in this cohort.METHODS: A total of 69 participants (27 inactive men, 18 indoor and 24 outdoor athletes) participated in the study. Vitamin D metabolites (25-(OH)DT, 24,25-(OH)2D3, 3-epi-25-(OH)D3, and 1,25-(OH)2D) were assessed using LC-MS/MS. The 25-(OH)DF concentration was calculated based on serum albumin and VDBP levels.RESULTS: There were no differences in vitamin D metabolites and VMRs between inactive men and between the two groups of athletes. We showed a strong relationship between 25-(OH)DT, 25-(OH)DF and 24,25-(OH)D3, 3-epi-25(OH)D3 in each group. Analysis showed that 25-(OH)DT, 25-(OH)DF inversely associated with 25-(OH)D3:24,25-(OH)2D3, 25-(OH)D3:3-epi-25-(OH)D3, 1,25-(OH)2D:24,25-(OH)2D3 ratios in inactive men and athletes (indoor and outdoor).CONCLUSIONS: On the basis of our results, we concluded that regular long-term physical activity has no effect on the concentration of vitamin D metabolites at rest. Furthermore, free vitamin D does not correlate more strongly with vitamin D metabolites and VMRs compared to total.PMID:37549820 | DOI:10.1016/j.cca.2023.117507

Food Chem. 2023 Aug 2;430:137087. doi: 10.1016/j.foodchem.2023.137087. Online ahead of print.ABSTRACTThe characterization of peach metabolites and carotenoids during canning and storage remains unclear. The present study identified 658 metabolites and 40 carotenoids in peach fruits throughout the canning and storage using ESI-MS/MS and APCI-MS/MS based metabolome approach. A total of 282 differentially accumulated metabolites were found, mainly including 78 phenolic acids, 74 lipids, 61 flavonoids. Five esterified carotenoids (rubixanthin palmitate, β-cryptoxanthin oleate, β-cryptoxanthin laurate, β-cryptoxanthin palmitate, and β-cryptoxanthin myristate) were the main peach carotenoids, with a proportion of approximately 90%, while free carotenoids accounted for 4.22-5.95% during the entire processing period. Moreover, the total carotenoid loss rates for canning and storage were 56.67% and 46.55%, respectively. Compared to the loss of free carotenoids, esterified carotenoids were more stable during storage, while canning led to a greater loss of esterified carotenoids. The results provided new insights into the maintenance of health-related phytochemicals from canning processes.PMID:37549620 | DOI:10.1016/j.foodchem.2023.137087

J Hazard Mater. 2023 Jul 29;459:132193. doi: 10.1016/j.jhazmat.2023.132193. Online ahead of print.ABSTRACTPerfluorooctanoic acid (PFOA) and microcystin-LR (MCLR) are pervasive pollutants in surface waters that induce significant toxic effects on aquatic organisms. However, the combined environmental risk of PFOA and MCLR remains unclear. To assess the toxic effects of PFOA and MCLR on submerged macrophytes and biofilms, Vallisneria natans was exposed to different concentrations of PFOA and MCLR (0.01, 0.1, 1.0 and 10.0 μg L-1). Vallisneria natans was sensitive to high concentrations of MCLR (10 μg L-1): plants exposed to 10 μg L-1 of MCLR measured a biomass of 3.46 g, which was significantly lower than the 8.71 g of the control group. Additionally, antagonistic interactive effects were observed in plants exposed to combined PFOA and MCLR. Exposure to these pollutants adversely affected photosynthesis of the plants and triggered peroxidation that promoted peroxidase, superoxide dismutase and catalase activities, and increased malondialdehyde and glutathione concentrations. The total chlorophyll content was lower in the highest concentration of the combined treatment group (0.443 mg g-1) than in the control group (0.534 mg g-1). Peroxidase activity increased from 662.63 U mg-1 Pr to 1193.45 U mg-1 Pr with increasing PFOA concentrations. Metabolomics indicated that the stress tolerance of Vallisneria natans was improved via altered fatty acid metabolism, hormone metabolism and carbon metabolism. Furthermore, PFOA and MCLR influenced the abundance and structure of the microbial community in the biofilms of Vallisneria natans. The increased contents of autoinducer peptide and N-acylated homoserine lactone signaling molecules indicated that these pollutants altered the formation and function of the biofilm. These results expand our understanding of the combined effects of PFOA and MCLR in aquatic ecosystems.PMID:37549579 | DOI:10.1016/j.jhazmat.2023.132193

Plant Physiol Biochem. 2023 Jul 31;202:107923. doi: 10.1016/j.plaphy.2023.107923. Online ahead of print.ABSTRACTSeed dormancy is a critical trait that enhances plant survival by preventing seed germination at the wrong time or under unsuitable conditions. Lack of seed dormancy in rice can lead to pre-harvest sprouting on mother plants leading to reduced yield and seed quality. Although some genes have been identified, knowledge of regulation of seed dormancy is limited. Here, we characterized a weak seed dormancy mutant named weak seed dormancy 1 (wsd1) that showed a higher seed germination percentage than the wild-type following the harvest ripeness. We cloned the WSD1 encoding an aminotransferase protein using a MutMap approach. WSD1 was stably expressed after imbibition and its protein was localized in the endoplasm reticulum. A widely targeted metabolomics assay and amino acid analysis showed that WSD1 had a role in regulating homeostasis of amino acids. PAC treatment and RNA-seq analysis showed that WSD1 regulates seed dormancy by involvement in the GA biosynthesis pathway. GA1 content and expression of GA biosynthesis-related genes were increased in the wsd1 mutant compared with the wild-type. The wsd1 mutant had reduced sensitivity to ABA. Our overall results indicated that WSD1 regulates seed dormancy by balancing the ABA and GA pathways.PMID:37549571 | DOI:10.1016/j.plaphy.2023.107923

J Ovarian Res. 2023 Aug 8;16(1):156. doi: 10.1186/s13048-023-01237-8.ABSTRACTBi-directional communication between cumulus cells and the surrounded oocytes is important for the development and functions of both compartments. However, the metabolic framework in cumulus cells has not been systematically described. In the present study, cumulus cells from cumulus-oocyte complexes (COCs) at three key time points were isolated (arrested GV stage, post-hCG 0h; meiotic resumption GVBD stage, post-hCG 3h; and metaphase II stage, post-hCG 12h), and the temporal metabolomic and proteomic profiling were performed. Integrated multi-omics analysis reveals the global metabolic patterns in cumulus cells during mouse oocyte maturation. In particular, we found the active hyaluronic acid metabolism, steroid hormone synthesis, and prostaglandin E2 (PGE2) production in cumulus cells. Meanwhile, accompanying the oocyte maturation, a progressive increase in nucleotide and amino acid metabolism was detected in the surrounding cumulus cells. In sum, the data serve as a valuable resource for probing metabolism during terminal differentiation of ovarian granulosa cells, and provide the potential biomarkers for improving and predicting oocyte quality.PMID:37550748 | DOI:10.1186/s13048-023-01237-8

Eur J Nutr. 2023 Aug 7. doi: 10.1007/s00394-023-03224-7. Online ahead of print.ABSTRACTPURPOSE: Child malnutrition is a global public health problem, but the underlying pathophysiologic mechanisms with severity remain poorly understood, and the potential biomarkers served to the clinical diagnosis are still not available. This study aimed to identify the serum metabolic characteristics of malnourished children with severity.METHODS: Fasted overnight serum samples were collected following clinical standard procedures among 275 malnourished and 199 healthy children from the Women and Children's Hospital, Xiamen University Child Health Department from July 2020 to May 2022. Nuclear magnetic resonance (NMR)-based metabolomics strategy was applied to identify the potential serum biomarkers of malnutrition from 275 malnourished children aged 4 to 84 months with mild (Mil, 199 cases), moderate (Mod, 101 cases), and severe (Sev, 7 cases) malnutrition.RESULTS: Ten, fifteen, and fifteen differential metabolites were identified from the Mil, Mod, and Sev malnutrition groups, respectively. Eight common metabolites, including increased acetoacetate, acetone, ethanol, succinate, 3-hydroxybutyrate, and decreased alanine, methionine, and N-acetyl-glycoprotein, could be the potential biomarkers for malnourished children. The altered metabolic pathways were mainly related to energy metabolism and amino acid metabolism via the network-based pathway enrichment.CONCLUSION: Eight potential biomarkers, including acetoacetate, acetone, ethanol, succinate, 3-hydroxybutyrate, alanine, methionine, and N-acetyl-glycoprotein, could characterize the child malnutrition. Child malnutrition-induced abnormal energy metabolism, impaired nutrition utilization and the reduced nutrient availability, and more metabolic disturbance will appear with the severity. Our results are valuable for further studies on the etiology and pathogenesis of malnutrition for clinical intervention and improvement.PMID:37550595 | DOI:10.1007/s00394-023-03224-7

Sci Rep. 2023 Aug 7;13(1):12772. doi: 10.1038/s41598-023-40027-6.ABSTRACTFew studies have provided data on the metabolomics characteristics of metabolic diseases such as hyperuricemia and hyperbilirubinemia in the Tibetan plateau. In the current study, we sought to investigate the serum metabolomics characteristics of hyperbilirubinemia and hyperuricemia in the Tibetan plateau, with the aim to provide a basis for further research on their pathogenesis, prevention, and treatment. The study participants were born in low-altitude areas below 1000 m and had no prior experience living in a high-altitude area before entering Golmud, Tibet (average elevation: 3000 m) and Yushu, Qinghai (average elevation: 4200 m). Thirty-four participants with hyperbilirubinemia (18 in Golmud and 16 in Yushu), 24 participants with hyperuricemia, and 22 healthy controls were enrolled. The serum samples of subjects were separated and then sent to a local tertiary hospital for biochemical examination. Serum widely targeted technology, based on the ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) platform, was used to detect serum metabolites and differential metabolites. Compared to the healthy controls, hyperbilirubinemia patients from Golmud showed 19 differential metabolites, hyperbilirubinemia patients from Yushu showed 12 differential metabolites, and hyperuricemia patients from Yushu showed 23 differential metabolites. Compared to the hyperbilirubinemia patients from Golmud that is at a low altitude, the Yushu groups had 33 different metabolites. Differential metabolites are primarily classified into amino acids and their derivatives, nucleotides and their derivatives, organic acids and their derivatives, and lipids/fatty acids. These are related to metabolic pathways such as caffeine metabolism, arachidonic acid metabolism, and tyrosine metabolism. Hyperbilirubinemia and hyperuricemia in the Tibetan plateau have unique serum metabolomics characteristics. Glycine derivatives and arachidonic acid and its derivatives were associated with plateau hyperbilirubinemia, and vanillic acid and pentadecafluorooctanoic acid were associated with plateau hyperuricemia.PMID:37550384 | DOI:10.1038/s41598-023-40027-6

ACS Appl Mater Interfaces. 2023 Aug 7. doi: 10.1021/acsami.3c04260. Online ahead of print.ABSTRACTPreterm birth (PTB) is the leading cause of infant deaths globally. Current clinical measures often fail to identify women who may deliver preterm. Therefore, accurate screening tools are imperative for early prediction of PTB. Here, we show that Raman spectroscopy is a promising tool for studying biological interfaces, and we examine differences in the maternal metabolome of the first trimester plasma of PTB patients and those that delivered at term (healthy). We identified fifteen statistically significant metabolites that are predictive of the onset of PTB. Mass spectrometry metabolomics validates the Raman findings identifying key metabolic pathways that are enriched in PTB. We also show that patient clinical information alone and protein quantification of standard inflammatory cytokines both fail to identify PTB patients. We show for the first time that synergistic integration of Raman and clinical data guided with machine learning results in an unprecedented 85.1% accuracy of risk stratification of PTB in the first trimester that is currently not possible clinically. Correlations between metabolites and clinical features highlight the body mass index and maternal age as contributors of metabolic rewiring. Our findings show that Raman spectral screening may complement current prenatal care for early prediction of PTB, and our approach can be translated to other patient-specific biological interfaces.PMID:37549133 | DOI:10.1021/acsami.3c04260