PubMed

Access Microbiol. 2023 Jun 29;5(6):acmi000432. doi: 10.1099/acmi.0.000432. eCollection 2023.ABSTRACTObjective. The present study was carried out to establish the chemical profile of the methanolic extract of Polyalthia longifolia stem bark and investigate its antibacterial property against some human pathogenic bacteria. Methods. The extract was analysed using liquid and gas chromatography coupled to mass spectrometry. Antibacterial activity of P. longifolia extract against some human pathogenic bacteria was screened using the AlamarBlue method, and MIC and MBC were determined. Results and Conclusion. Liquid chromatography-mass spectrometry (LC-MS) revealed the presence of 21 compounds among which 12 were identified. Gas chromatography-mass spectrometry (GC-MS) allowed identification of 26 compounds, the three major ones being the following: cis vaccenic acid (17.79 %), 3-ethyl-3-hydroxyandrostan-17-one (13.80 %) and copaiferic acid B (12.82 %). P. longifolia extract was active against Gram-positive bacteria with MIC ranging from 1 to 2 mg ml-1 and MBC from 2 to 6 mg ml-1. This study demonstrated the bactericidal effect of the methanolic extract of Polyalthia longifolia stem bark against some human pathogenic bacteria, including methicillin-resistant S. aureus . This effect could be related to the presence in the extract of a broad diversity of well-known compounds with established pharmacological properties. These results support the ethnomedicinal use of P. longifolia stem bark in Cameroon for the management of methicillin-resistant S. aureus (MRSA)-related infections.PMID:37424570 | PMC:PMC10323783 | DOI:10.1099/acmi.0.000432

Access Microbiol. 2023 Jun 28;5(6):acmi000535.v5. doi: 10.1099/acmi.0.000535.v5. eCollection 2023.ABSTRACTClitoria ternatea flowers are rich in anthocyanins and possess various biological activities. Specifically, the antibacterial mechanism of action of C. ternatea anthocyanins remains unknown and was investigated in Escherichia coli . A time-kill assay was used to assess the antibacterial activity and the metabolic perturbations in E. coli were investigated utilizing liquid chromatography-mass spectrometry (LC-MS)-based metabolomics. Pathway analyses were carried out for metabolites showing ≥2-fold changes. The anthocyanin fraction remarkably reduced the growth of E. coli at 4 h by 95.8 and 99.9 % at minimum inhibitory concentration (MIC) and 2× MIC, respectively. The anthocyanin fraction (MIC) had a bacteriostatic effect and was shown to have perturbed glycerophospholipids (1-acyl-sn-glycero-3-phosphoethanolamine, phosphatidylglycerol, diacylglycerol and cardiolipin), amino acids (valine, tyrosine and isoleucine) and energy (ubiquinone and NAD) metabolites at 1 and 4 h. This study demonstrated significant metabolic perturbations of the glycerophospholipid, amino acid and energy metabolism, with these being the key pathways involved in the bacteriostatic activity of anthocyanins from C. ternatea, which may have promise as bacteriostatic agents for E. coli -related infections.PMID:37424541 | PMC:PMC10323780 | DOI:10.1099/acmi.0.000535.v5

Biotechnol Bioeng. 2023 Jul 10. doi: 10.1002/bit.28494. Online ahead of print.ABSTRACTHuman macrophages are innate immune cells with diverse, functionally distinct phenotypes, namely, pro-inflammatory M1 and anti-inflammatory M2 macrophages. Both are involved in multiple physiological and pathological processes, including would healing, infection, and cancer. However, the metabolic differences between these phenotypes are largely unexplored at single-cell resolution. To address this knowledge gap, an untargeted live single-cell mass spectrometry-based metabolomic profiling coupled with a machine-learning data analysis approach was developed to investigate the metabolic profile of each phenotype at the single-cell level. Results show that M1 and M2 macrophages have distinct metabolic profiles, with differential levels of fatty acyls, glycerophospholipids, and sterol lipids, which are important components of plasma membrane and involved in multiple biological processes. Furthermore, we could discern several putatively annotated molecules that contribute to inflammatory response of macrophages. The combination of random forest and live single-cell metabolomics provided an in-depth profile of the metabolome of primary human M1 and M2 macrophages at the single-cell level for the first time, which will pave the way for future studies targeting the differentiation of other immune cells.PMID:37424521 | DOI:10.1002/bit.28494

J Alzheimers Dis. 2023 Jul 7. doi: 10.3233/JAD-230291. Online ahead of print.ABSTRACTBACKGROUND: Characterizing the periodontal status of patients with Alzheimer's disease (AD), investigating differences in salivary metabolism between patients with and without AD under the same periodontal conditions, and understanding how it is related to oral flora are critical.OBJECTIVE: We aimed to examine the periodontal condition of patients with AD and to screen salivary metabolic biomarkers from the saliva of individuals with and without AD with matched periodontal conditions. Furthermore, we aimed to explore the possible relationship between salivary metabolic changes and oral flora.METHODS: In total, 79 individuals were recruited into the experiment for periodontal analysis. Especially, 30 saliva samples from the AD group and 30 from healthy controls (HCs) with matched periodontal conditions were selected for metabolomic analysis. The random-forest algorithm was used to detect candidate biomarkers. Among these, 19 AD saliva and 19 HC samples were selected to investigate the microbiological factors influencing the alterations in saliva metabolism in patients with AD.RESULTS: The plaque index and bleeding on probing were considerably higher in the AD group. Further, Cis-3-(1-carboxy-ethyl)-3,5-cyclohexadiene-1,2-diol, dodecanoic acid, genipic acid, and N, N-dimethylthanolamine N-oxide were determined as candidate biomarkers, based on the area under the curve (AUC) value (AUC = 0.95). The results of oral-flora sequencing showed that dysbacteriosis may be a reason for the differences in AD saliva metabolism.CONCLUSION: Dysregulation of the proportion of specific bacterial flora in saliva plays a vital role in metabolic changes in AD. These results will contribute to further improving the AD saliva biomarker system.PMID:37424468 | DOI:10.3233/JAD-230291

Gut Microbes. 2023 Jan-Dec;15(1):2233149. doi: 10.1080/19490976.2023.2233149.ABSTRACTIntestinal stem cells (ISCs) are critical for the development and rapid turnover of intestinal epithelium. The regulatory effects of gut microbiota and their metabolites on ISCs stemness remain elusive. Fucose has been demonstrated to mediate host-microbe interactions in the intestine. However, the association between fucose, gut bacteria, and ISCs stemness remains unclear. To investigate the effects of fucose on ISCs-mediated intestinal epithelial cells (IECs) development, we administered fucose to 4-week-old mice for 4 weeks. ISCs stemness, IECs proliferation, and differentiation were examined. Variations in gut microbes and metabolism were detected using 16S rDNA sequencing and metabolomic analysis. Fucose was added to the bacterial culture medium to further study its effects on metabolism. Crypts were isolated from the mouse ileum for organoids culture in vitro to evaluate the effects of metabolites and the underlying mechanism. The results showed that fucose accelerated ISCs proliferation and secretory lineage differentiation in mice, whereas antibiotics eliminated these effects. The composition and functions of gut bacteria were altered by fucose treatment, while significant increases in Akkermansia and propanoate metabolism were noted. Propionic acid and propionate have been shown to promote organoid development. Fucose fermentation increases the production of propionic acid in Akkermansia muciniphila and enhances its ability to increase the stemness of ISCs. Moreover, ileal contents from fucose-treated mice promoted organoid development in a Gpr41/Gpr43-dependent manner. Fucose administration activates the Wnt signaling pathway in ISCs, and Wnt inhibitors suppress the effects of fucose. We conclude that fucose accelerates ISC-mediated intestinal epithelial development by promoting Akkermansia-related propanoate metabolism. These findings provide new insights into the promotion of gut homeostasis and the application potential of fucose as a prebiotic.PMID:37424378 | DOI:10.1080/19490976.2023.2233149

Comb Chem High Throughput Screen. 2023 Jul 7. doi: 10.2174/1386207326666230707110651. Online ahead of print.ABSTRACTBACKGROUND: An endophytic fungal strain Penicillium crustosum was isolated from the seagrass Posidonia oceanica and investigated to identify its antimicrobial constituents and characterize its metabolome composition. The ethyl acetate extract of this fungus exhibited antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) as well as an anti-quorum sensing effect against Pseudomonas aeruginosa.METHODS: The crude extract was profiled by UHPLC-HRMS/MS and the dereplication was assisted by feature-based molecular networking. As a result, more than twenty compounds were annotated in this fungus. To rapidly identify the active compounds, the enriched extract was fractionated by semi-preparative HPLC-UV applying a chromatographic gradient transfer and dry load sample introduction to maximise resolution. The collected fractions were profiled by 1H-NMR and UHPLC-HRMS.RESULTS: The use of molecular networking-assisted UHPLC-HRMS/MS dereplication allowed preliminary identification of over 20 compounds present in the ethyl acetate extract of P. crustosum. The chromatographic approach significantly accelerated the isolation of the majority of compounds present in the active extract. The one-step fractionation allowed the isolation and identification of eight compounds (1-8).CONCLUSION: This study led to the unambiguous identification of eight known secondary metabolites as well as the determination of their antibacterial properties.PMID:37424340 | DOI:10.2174/1386207326666230707110651

Gut Microbes. 2023 Jan-Dec;15(1):2231596. doi: 10.1080/19490976.2023.2231596.ABSTRACTThe gut microbiota is involved in the production of numerous metabolites that maintain host wellbeing. The assembly of the gut microbiome is highly dynamic, and influenced by many postnatal factors, moreover, little is known about the development of the gut metabolome. We showed that geography has an important influence on the microbiome dynamics in the first year of life based on two independent cohorts from China and Sweden. Major compositional differences since birth were the high relative abundance of Bacteroides in the Swedish cohort and Streptococcus in the Chinese cohort. We analyzed the development of the fecal metabolome in the first year of life in the Chinese cohort. Lipid metabolism, especially acylcarnitines and bile acids, was the most abundant metabolic pathway in the newborn gut. Delivery mode and feeding induced particular differences in the gut metabolome since birth. In contrast to C-section newborns, medium- and long-chain acylcarnitines were abundant at newborn age only in vaginally delivered infants, associated by the presence of bacteria such as Bacteroides vulgatus and Parabacteroides merdae. Our data provide a basis for understanding the maturation of the fecal metabolome and the metabolic role of gut microbiota in infancy.PMID:37424334 | DOI:10.1080/19490976.2023.2231596

Biomed Environ Sci. 2023 Jun 20;36(6):537-541. doi: 10.3967/bes2023.065.NO ABSTRACTPMID:37424247 | DOI:10.3967/bes2023.065

Immunol Rev. 2023 Jul 9. doi: 10.1111/imr.13235. Online ahead of print.ABSTRACTFerroptosis is a form of iron-dependent regulated cell death characterized by the accumulation of toxic lipid peroxides, particularly in the plasma membrane, leading to lytic cell death. While it plays a crucial role in maintaining the overall health and proper functioning of multicellular organisms, it can also contribute to tissue damage and pathological conditions. Although ferroptotic damage is generally recognized as an immunostimulatory process associated with the release of damage-associated molecular patterns (DAMPs), the occurrence of ferroptosis in immune cells or the release of immunosuppressive molecules can result in immune tolerance. Consequently, there is ongoing exploration of targeting the upstream signals or the machinery of ferroptosis to therapeutically enhance or inhibit the immune response. In addition to introducing the core molecular mechanisms of ferroptosis, we will focus on the immune characteristics of ferroptosis in pathological conditions, particularly in the context of infection, sterile inflammation, and tumor immunity.PMID:37424139 | DOI:10.1111/imr.13235

Mol Nutr Food Res. 2023 Jul 9:e2200883. doi: 10.1002/mnfr.202200883. Online ahead of print.ABSTRACTSCOPE: Soybean 7S globulin (β-conglycinin), a major soybean storage protein, has been demonstrated to exert remarkable triglyceride (TG) and cholesterol-lowering effects, yet the underlying mechanism remains controversial.METHODS AND RESULTS: A comparative investigation is performed to assess the contribution of different structural domains of soybean 7S globulin, including core region (CR) and extension region (ER) domains, to biological effects of soybean 7S globulin using a high-fat diet rat model. The results show that ER domain mainly contributes to the serum TG-lowering effect of soybean 7S globulin, but not for CR domain. Metabolomics analysis reveals that oral administration of ER peptides obviously influences the metabolic profiling of serum bile acids (BAs), as well as significantly increased the fecal excretion of total BAs. Meanwhile, ER peptides supplementation reshapes the composition of gut microbiota and impacts the gut microbiota-dependent biotransformation of BAs which indicate by a significantly increased secondary BAs concentration in fecal samples. These results highlight that TG-lowering effects of ER peptides mainly stem from their modulation of BAs homeostasis.CONCLUSION: Oral administration of ER peptides can effectively lower serum TG level by regulating BAs metabolism. ER peptides have potential to be used as a candidate pharmaceutical for the intervention of dyslipidemia.PMID:37423975 | DOI:10.1002/mnfr.202200883

Br J Haematol. 2023 Jul 9. doi: 10.1111/bjh.18939. Online ahead of print.ABSTRACTGrowth factor independence 1 (GFI1) is a transcriptional repressor protein that plays an essential role in the differentiation of myeloid and lymphoid progenitors. We and other groups have shown that GFI1 has a dose-dependent role in the initiation, progression, and prognosis of acute myeloid leukaemia (AML) patients by inducing epigenetic changes. We now demonstrate a novel role for dose-dependent GFI1 expression in regulating metabolism in haematopoietic progenitor and leukaemic cells. Using in-vitro and ex-vivo murine models of MLL::AF9-induced human AML and extra-cellular flux assays, we now demonstrate that a lower GFI1 expression enhances oxidative phosphorylation rate via upregulation of the FOXO1- MYC axis. Our findings underscore the significance of therapeutic exploitation in GFI1-low-expressing leukaemia cells by targeting oxidative phosphorylation and glutamine metabolism.PMID:37423893 | DOI:10.1111/bjh.18939

Anal Chim Acta. 2023 Sep 8;1273:341537. doi: 10.1016/j.aca.2023.341537. Epub 2023 Jun 21.ABSTRACTDespite the advances in low-field nuclear magnetic resonance (NMR), there are limited spectroscopic applications for untargeted analysis and metabolomics. To evaluate its potential, we combined high-field and low-field NMR with chemometrics for the differentiation between virgin and refined coconut oil and for the detection of adulteration in blended samples. Although low-field NMR has less spectral resolution and sensitivity compared to high-field NMR, it was still able to achieve a differentiation between virgin and refined coconut oils, as well as between virgin coconut oil and blends, using principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and random forest techniques. These techniques were not able to distinguish between blends with different levels of adulteration; however, partial least squares regression (PLSR) enabled the quantification of adulteration levels for both NMR approaches. Given the significant benefits of low-field NMR, including economic and user-friendly analysis and fitting in an industrial environment, this study establishes the proof of concept for its utilization in the challenging scenario of coconut oil authentication. Also, this method has the potential to be used for other similar applications that involve untargeted analysis.PMID:37423668 | DOI:10.1016/j.aca.2023.341537

Anal Chim Acta. 2023 Sep 8;1273:341495. doi: 10.1016/j.aca.2023.341495. Epub 2023 Jun 6.ABSTRACTLow-field nuclear magnetic resonance (NMR) has three general modalities: spectroscopy, imaging, and relaxometry. In the last twelve years, the modality of spectroscopy, also known as benchtop NMR, compact NMR, or just low-field NMR, has undergone instrumental development due to new permanent magnetic materials and design. As a result, benchtop NMR has emerged as a powerful analytical tool for use in process analytical control (PAC). Nevertheless, the successful application of NMR devices as an analytical tool in several areas is intrinsically linked to its coupling with different chemometric methods. This review focuses on the evolution of benchtop NMR and chemometrics in chemical analysis, including applications in fuels, foods, pharmaceuticals, biochemicals, drugs, metabolomics, and polymers. The review also presents different low-resolution NMR methods for spectrum acquisition and chemometric techniques for calibration, classification, discrimination, data fusion, calibration transfer, multi-block and multi-way.PMID:37423658 | DOI:10.1016/j.aca.2023.341495

Cancer Lett. 2023 Jul 7:216305. doi: 10.1016/j.canlet.2023.216305. Online ahead of print.ABSTRACTAs essential modulators of transcription and translation, RNA-binding proteins (RBPs) are frequently dysregulated in cancer. Bioinformatics study reveals that the RNA-binding protein hexokinase domain component 1 (HKDC1) is overexpressed in gastric cancer (GC). As HKDC1 plays a role in lipid homeostasis in the liver and glucose metabolism in certain cancers, the exact mechanism of action of HKDC1 in GC remains largely unknown. Upregulation of HKDC1 correlates with chemoresistance and poor prognosis in GC patients. HKDC1 enhances invasion, migration and resistance to cisplatin (CDDP) in GC cells in vitro and in vivo. Comprehensive transcriptomic sequencing and metabolomic analysis reveal that HKDC1 mediates abnormal lipid metabolism in GC cells. Herein, we identify a number of HKDC1-binding endogenous RNAs in GC cells, including protein kinase, DNA-activated, catalytic subunit (PRKDC) mRNA. We further validate that PRKDC is a crucial downstream effector of HKDC1 induced-GC tumorigenesis depends on lipid metabolism. Interestingly, G3BP1, a well-known oncoprotein, can be bound by HKDC1. HKDC1 cooperates with G3BP1 to enhance the stability of PRKDC transcript. Our results reveal a novel HKDC1/G3BP1-PRKDC regulatory axis that induces GC metastasis and chemoresistance via reprogramming lipid metabolism, which may provide an effective therapeutic strategy for a subset of GC with HKDC1 overexpression.PMID:37423558 | DOI:10.1016/j.canlet.2023.216305

J Ethnopharmacol. 2023 Jul 7:116893. doi: 10.1016/j.jep.2023.116893. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Buyang Huanwu decoction (BHD), a famous traditional Chinese medicine (TCM) formula, was first recorded in Qing Dynasty physician Qingren Wang's Yi Lin Gai Cuo. BHD has been widely utilized in the treatment of patients with neurological disorders, including Parkinson's disease (PD). However, the underlying mechanism has not been fully elucidated. In particular, little is known about the role of gut microbiota.AIM OF THE STUDY: We aimed to reveal the alterations and functions of gut microbiota and its correlation with the liver metabolome in the process of improving PD with BHD.MATERIALS AND METHODS: The cecal contents were collected from PD mice treated with or without BHD. 16S rRNA gene sequencing was performed on an Illumina MiSeq-PE250 platform, and the ecological structure, dominant taxa, co-occurrence patterns, and function prediction of the gut microbial community were analyzed by multivariate statistical methods. The correlation between differential microbial communities in the gut and differentially accumulated metabolites in the liver was analyzed using Spearman's correlation analysis.RESULTS: The abundance of Butyricimonas, Christensenellaceae, Coprococcus, Peptococcaceae, Odoribacteraceae, and Roseburia was altered significantly in the model group, which was by BHD. Ten genera, namely Dorea, unclassified_Lachnospiraceae, Oscillospira, unidentified_Ruminococcaceae, unclassified_Clostridiales, unidentified_Clostridiales, Bacteroides, unclassified_Prevotellaceae, unidentified_Rikenellaceae, and unidentified_S24-7, were identified as key bacterial communities. According to the function prediction of differential genera, the mRNA surveillance pathway might be a target of BHD. Integrated analysis of gut microbiota and the liver metabolome revealed that several gut microbiota genera such as Parabacteroides, Ochrobactrum, Acinetobacter, Clostridium, and Halomonas, were positively or negatively correlated with some nervous system-related metabolites, such as L-carnitine, L-pyroglutamic acid, oleic acid, and taurine.CONCLUSIONS: Gut microbiota might be a target of BHD in the process of ameliorating PD. Our findings provide novel insight into the mechanisms underlying the effects of BHD on PD and contribute to the development of TCM.PMID:37423520 | DOI:10.1016/j.jep.2023.116893

Chemosphere. 2023 Jul 7:139446. doi: 10.1016/j.chemosphere.2023.139446. Online ahead of print.ABSTRACTThe health of the aquatic ecosystem has recently been severely affected by cyanobacterial blooms brought on by eutrophication. Therefore, it is critical to develop efficient and secure methods to control dangerous cyanobacteria, such as Microcystis aeruginosa. In this research, we tested the inhibition of M. aeruginosa growth by a Scenedesmus sp. strain isolated from a culture pond. Scenedesmus sp. culture filtrate that had been lyophilized was added to M. aeruginosa, and cultivation for seven days, the cell density, chlorophyll a (Chl-a) concentration, maximum quantum yield of photosystem II (Fv/Fm), the activities of superoxide dismutase (SOD), catalase (CAT), and the concentration of malondialdehyde (MDA) and glutathione (GSH) were measured. Moreover, non-targeted metabolomics was carried out to provide light on the inhibitory mechanism in order to better understand the metabolic response. According to the results, M. aeruginosa is effectively inhibited by the lyophilized Scenedesmus sp. culture filtrate at a rate of 51.2%. Additionally, the lyophilized Scenedesmus sp. clearly inhibit the photosystem and damages the antioxidant defense system of M. aeruginosa cells, resulting in oxidative damage, which worsens membrane lipid peroxidation, according to changes in Chl-a, Fv/Fm, SOD, CAT enzyme activities and MDA, GSH. Metabolomics analysis revealed that the secondary metabolites of Scenedesmus sp. significantly interfere with the metabolism of M. aeruginosa involved in amino acid synthesis, membrane creation and oxidative stress, which is coherent with the morphology and physiology outcomes. These results demonstrate that the secondary metabolites of Scenedesmus sp. exert algal inhibition effect by breaked the membrane structure, destroyed the photosynthetic system of microalgae, inhibited amino acid synthesis, reduced antioxidant capacity, and eventually caused algal cell lysis and death. Our research provides a reliable basis for the biological control of cyanobacterial blooms on the one hand, and on other hand supply application of non-targeted metabolome on the study of microalgae allelochemicals.PMID:37423414 | DOI:10.1016/j.chemosphere.2023.139446

Life Sci. 2023 Jul 7:121912. doi: 10.1016/j.lfs.2023.121912. Online ahead of print.ABSTRACTAIMS: The present study aims to investigate the impact of the gut microbiota and serum metabolites on the regulation of liver dysfunction in PCOS.MATERIALS AND METHODS: PCOS rat models were established by treating Sprague Dawley (SD) rats with DHEA (an androgen, 60 mg/kg) and LET (a nonsteroidal aromatase inhibitor, 1 mg/kg) for 90 days. Hematoxylin and eosin staining (H&E), Western blotting, and radioimmunoassay were employed to test ovarian and liver functions. Gut microbiome and serum metabolites were assessed using 16S rRNA amplicon sequencing and non-targeted metabolomics, respectively. The association between gut microbiota and serum metabolites was examined using Spearman analysis. Finally, using HepG2 cells to investigate the function of the serum metabolite rosmarinic acid (RA).KEY FINDINGS: Both Dehydroepiandrosterone (DHEA) and letrozole (LET) treatments induced a PCOS phenotype and liver dysfunction. However, LET resulted in more severe lipid accumulation and liver cell apoptosis than DHEA. 16S rRNA sequencing and non-targeted metabolomics analysis revealed significant differences in beta diversity and serum metabolite profiles among the three groups. Furthermore, among the significantly changed metabolites, RA was found to have a significant correlation with the levels of serum aspartate transaminase (AST) and lactate dehydrogenase (LDH) and could promote HepG2 cell apoptosis.SIGNIFICANCE: Restoring gut microbiota, altering serum metabolites and/or decreasing RA may provide a new insight to treat this complication.PMID:37423380 | DOI:10.1016/j.lfs.2023.121912

Sci Total Environ. 2023 Jul 7:165379. doi: 10.1016/j.scitotenv.2023.165379. Online ahead of print.ABSTRACTDreissena polymorpha is a bivalve promising for biomonitoring in freshwater ecosystems thanks to its abundance and high filtration activity allowing rapid uptake of toxicants and identification of their negative effects. Nonetheless, we still lack knowledge on its molecular responses to stress under realistic scenario, e.g. multi-contamination. Carbamazepine (CBZ) and Hg are ubiquitous pollutants sharing molecular toxicity pathways, e.g. oxidative stress. A previous study in zebra mussels showed their co-exposure to cause more disturbing alterations than single exposures, but molecular toxicity pathways remained unidentified. D. polymorpha was exposed 24 h (T24) and 72 h (T72) to CBZ (6.1 ± 0.1 μg L-1), MeHg (430 ± 10 ng L-1) and the co-exposure (6.1 ± 0.1 μg L-1CBZ and 500 ± 10 ng L-1 MeHg) at concentrations representative of polluted areas (~10× EQS). RedOx system at the gene and enzyme level, the proteome and the metabolome were compared. The co-exposure resulted in 108 differential abundant proteins (DAPs), as well as 9 and 10 modulated metabolites at T24 and T72, respectively. The co-exposure specifically modulated DAPs and metabolites involved in neurotransmission, e.g. dopaminergic synapse and GABA. CBZ specifically modulated 46 DAPs involved in calcium signaling pathways and 7 amino acids at T24. MeHg specifically modulated 55 DAPs proteins involved in the cytoskeleton remodeling and hypoxia-induced factor 1 pathway, without altering the metabolome. Single and co-exposures commonly modulated proteins and metabolites involved in energy and amino acid metabolisms, response to stress and development. Concomitantly, lipid peroxidation and antioxidant activities were unchanged, supporting that D. polymorpha tolerated experimental conditions. The co-exposure was confirmed to cause more alterations than single exposures. This was attributed to the combined toxicity of CBZ and MeHg. Altogether, this study underlined the necessity to better characterize molecular toxicity pathways of multi-contamination that are not predictable on responses to single exposures, to better anticipate adverse effects in biota and improve risk assessment.PMID:37423277 | DOI:10.1016/j.scitotenv.2023.165379

Redox Biol. 2023 Jul 5;65:102808. doi: 10.1016/j.redox.2023.102808. Online ahead of print.ABSTRACTPrecision nutrition aims to deliver personalised dietary advice to individuals based on their personal genetics, metabolism and dietary/environmental exposures. Recent advances have demonstrated promise for the use of omic technologies for furthering the field of precision nutrition. Metabolomics in particular is highly attractive as measurement of metabolites can capture information on food intake, levels of bioactive compounds and the impact of diets on endogenous metabolism. These aspects contain useful information for precision nutrition. Furthermore using metabolomic profiles to identify subgroups or metabotypes is attractive for the delivery of personalised dietary advice. Combining metabolomic derived metabolites with other parameters in prediction models is also an exciting avenue for understanding and predicting response to dietary interventions. Examples include but not limited to role of one carbon metabolism and associated co-factors in blood pressure response. Overall, while evidence exists for potential in this field there are also many unanswered questions. Addressing these and clearly demonstrating that precision nutrition approaches enable adherence to healthier diets and improvements in health will be key in the near future.PMID:37423161 | DOI:10.1016/j.redox.2023.102808

Diabetes Metab Res Rev. 2023 Jul 9:e3685. doi: 10.1002/dmrr.3685. Online ahead of print.ABSTRACTAIMS/HYPOTHESIS: Inflammation is important in the development of type 2 diabetes complications. The N-glycosylation of IgG influences its role in inflammation. To date, the association of plasma IgG N-glycosylation with type 2 diabetes complications has not been extensively investigated. We hypothesised that N-glycosylation of IgG may be related to the development of complications of type 2 diabetes.METHODS: In three independent type 2 diabetes cohorts, plasma IgG N-glycosylation was measured using ultra performance liquid chromatography (DiaGene n = 1815, GenodiabMar n = 640) and mass spectrometry (Hoorn Diabetes Care Study n = 1266). We investigated the associations of IgG N-glycosylation (fucosylation, galactosylation, sialylation and bisection) with incident and prevalent nephropathy, retinopathy and macrovascular disease using Cox- and logistic regression, followed by meta-analyses. The models were adjusted for age and sex and additionally for clinical risk factors.RESULTS: IgG galactosylation was negatively associated with prevalent and incident nephropathy and macrovascular disease after adjustment for clinical risk factors. Sialylation was negatively associated with incident diabetic nephropathy after adjustment for clinical risk factors. For incident retinopathy, similar associations were found for galactosylation, adjusted for age and sex.CONCLUSIONS: We showed that IgG N-glycosylation, particularly galactosylation and to a lesser extent sialylation, is associated with a higher prevalence and future development of macro- and microvascular complications of diabetes. These findings indicate the predictive potential of IgG N-glycosylation in diabetes complications and should be analysed further in additional large cohorts to obtain the power to solidify these conclusions.PMID:37422864 | DOI:10.1002/dmrr.3685