PubMed

bioRxiv. 2023 Jun 26:2023.06.23.546277. doi: 10.1101/2023.06.23.546277. Preprint.ABSTRACTAutism spectrum disorder (ASD) is a neurodevelopmental disorder with various proposed environmental risk factors and a rapidly increasing prevalence. Mounting evidence suggests a potential role of vitamin D deficiency in ASD pathogenesis, though causal mechanisms remain largely unknown. Here, we investigate the impact of vitamin D on child neurodevelopment through an integrative network approach that combines metabolomic profiles, clinical traits, and neurodevelopmental data from a pediatric cohort. Our results show that vitamin D deficiency is associated with changes in the metabolic networks of tryptophan, linoleic, and fatty acid metabolism. These changes correlate with distinct ASD-related outcomes, including delayed communication skills and respiratory dysfunctions. Additionally, our analysis suggests the kynurenine and serotonin sub-pathways might mediate the effect of vitamin D on early childhood communication development. Altogether, our findings provide metabolome-wide insights into the potential of vitamin D as a therapeutic option for ASD and other communication disorders.PMID:37425858 | PMC:PMC10327084 | DOI:10.1101/2023.06.23.546277

medRxiv. 2023 Jun 29:2023.06.26.23291676. doi: 10.1101/2023.06.26.23291676. Preprint.ABSTRACTMuch of the high mortality in tuberculosis meningitis (TBM) is attributable to excessive inflammation, making it imperative to identify targets for host-directed therapies that reduce pathologic inflammation and mortality. In this study, we investigate how cytokines and metabolites in the cerebral spinal fluid (CSF) associate with TBM at diagnosis and during TBM treatment. At diagnosis, TBM patients demonstrate significant increases versus controls of cytokines and chemokines that promote inflammation and cell migration including IL-17A, IL-2, TNFα, IFNγ, and IL-1β. Inflammatory immune signaling was strongly correlated with immunomodulatory metabolites including kynurenine, lactic acid, carnitine, tryptophan, and itaconate. Inflammatory immunometabolic networks were only partially reversed with two months of effective TBM treatment and remained significantly different versus control CSF. Together, these data highlight a critical role for host metabolism in regulating the inflammatory response to TBM and indicate the timeline for restoration of immune homeostasis in the CSF is prolonged.PMID:37425849 | PMC:PMC10327257 | DOI:10.1101/2023.06.26.23291676

medRxiv. 2023 Jun 29:2023.06.26.23291721. doi: 10.1101/2023.06.26.23291721. Preprint.ABSTRACTMetabolites are small molecules that are useful for estimating disease risk and elucidating disease biology. Nevertheless, their causal effects on human diseases have not been evaluated comprehensively. We performed two-sample Mendelian randomization to systematically infer the causal effects of 1,099 plasma metabolites measured in 6,136 Finnish men from the METSIM study on risk of 2,099 binary disease endpoints measured in 309,154 Finnish individuals from FinnGen. We identified evidence for 282 causal effects of 70 metabolites on 183 disease endpoints (FDR<1%). We found 25 metabolites with potential causal effects across multiple disease domains, including ascorbic acid 2-sulfate affecting 26 disease endpoints in 12 disease domains. Our study suggests that N-acetyl-2-aminooctanoate and glycocholenate sulfate affect risk of atrial fibrillation through two distinct metabolic pathways and that N-methylpipecolate may mediate the causal effect of N6, N6-dimethyllysine on anxious personality disorder. This study highlights the broad causal impact of plasma metabolites and widespread metabolic connections across diseases.PMID:37425837 | PMC:PMC10327254 | DOI:10.1101/2023.06.26.23291721

bioRxiv. 2023 Jun 30:2023.06.30.546730. doi: 10.1101/2023.06.30.546730. Preprint.ABSTRACTPartial reprogramming by cyclic short-term expression of Yamanaka factors holds promise for shifting cells to younger states and consequently delaying the onset of many diseases of aging. However, the delivery of transgenes and potential risk of teratoma formation present challenges for in vivo applications. Recent advances include the use of cocktails of compounds to reprogram somatic cells, but the characteristics and mechanisms of partial cellular reprogramming by chemicals remain unclear. Here, we report a multi-omics characterization of partial chemical reprogramming in fibroblasts from young and aged mice. We measured the effects of partial chemical reprogramming on the epigenome, transcriptome, proteome, phosphoproteome, and metabolome. At the transcriptome, proteome, and phosphoproteome levels, we saw widescale changes induced by this treatment, with the most notable signature being an upregulation of mitochondrial oxidative phosphorylation. Furthermore, at the metabolome level, we observed a reduction in the accumulation of aging-related metabolites. Using both transcriptomic and epigenetic clock-based analyses, we show that partial chemical reprogramming reduces the biological age of mouse fibroblasts. We demonstrate that these changes have functional impacts, as evidenced by changes in cellular respiration and mitochondrial membrane potential. Taken together, these results illuminate the potential for chemical reprogramming reagents to rejuvenate aged biological systems, and warrant further investigation into adapting these approaches for in vivo age reversal.PMID:37425825 | PMC:PMC10327104 | DOI:10.1101/2023.06.30.546730

medRxiv. 2023 Jun 27:2023.06.21.23291103. doi: 10.1101/2023.06.21.23291103. Preprint.ABSTRACTRATIONALE: Arterial and venous cardiovascular conditions, such as coronary artery disease (CAD), peripheral artery disease (PAD), and venous thromboembolism (VTE), are genetically correlated. Interrogating distinct and overlapping mechanisms may shed new light on disease mechanisms.OBJECTIVE: In this study, we aimed to: identify and compare (1) epidemiologic and (2) causal, genetic relationships between metabolites and CAD, PAD, and VTE.METHODS: We used metabolomic data from 95,402 individuals in the UK Biobank, excluding individuals with prevalent cardiovascular disease. Logistic regression models adjusted for age, sex, genotyping array, first five principal components of ancestry, and statin use estimated the epidemiologic associations of 249 metabolites with incident CAD, PAD, or VTE. Bidirectional two-sample Mendelian randomization (MR) estimated the causal effects between metabolites and cardiovascular phenotypes using genome-wide association summary statistics for metabolites (N = 118,466 from UK Biobank), CAD (N = 184,305 from CARDIoGRAMplusC4D 2015), PAD (N = 243,060 from Million Veterans Project) and VTE (N = 650,119 from Million Veterans Project). Multivariable MR (MVMR) was performed in subsequent analyses.RESULTS: We found that 194, 111, and 69 metabolites were epidemiologically associated (P < 0.001) with CAD, PAD, and VTE, respectively. Metabolomic profiles exhibited variable similarity between disease pairs: CAD and PAD (N = 100 shared associations, R 2 = 0.499), CAD and VTE (N = 68, R 2 = 0.455), and PAD and VTE (N = 54, R 2 = 0.752). MR revealed 28 metabolites that increased risk for both CAD and PAD and 2 metabolites that increased risk for CAD but decreased risk for VTE. Despite strong epidemiologic overlap, no metabolites had a shared genetic relationship between PAD and VTE. MVMR revealed several metabolites with shared causal effects on CAD and PAD related to cholesterol content within very-low-density lipoprotein particles.CONCLUSIONS: While common arterial and venous conditions are associated with overlapping metabolomic profiles, MR prioritized the role of remnant cholesterol in arterial diseases but not venous thrombosis.PMID:37425786 | PMC:PMC10327201 | DOI:10.1101/2023.06.21.23291103

bioRxiv. 2023 Jun 29:2023.06.26.546628. doi: 10.1101/2023.06.26.546628. Preprint.ABSTRACTCombined multi-omics analysis of proteomics, polar metabolomics, and lipidomics requires separate liquid chromatography-mass spectrometry (LC-MS) platforms for each omics layer. This requirement for different platforms limits throughput and increases costs, preventing the application of mass spectrometry-based multi-omics to large scale drug discovery or clinical cohorts. Here, we present an innovative strategy for simultaneous multi-omics analysis by direct infusion (SMAD) using one single injection without liquid chromatography. SMAD allows quantification of over 9,000 metabolite m/z features and over 1,300 proteins from the same sample in less than five minutes. We validated the efficiency and reliability of this method and then present two practical applications: mouse macrophage M1/M2 polarization and high throughput drug screening in human 293T cells. Finally, we demonstrate relationships between proteomic and metabolomic data are discovered by machine learning.PMID:37425781 | PMC:PMC10326973 | DOI:10.1101/2023.06.26.546628

medRxiv. 2023 Jul 1:2023.06.28.23291995. doi: 10.1101/2023.06.28.23291995. Preprint.ABSTRACTBACKGROUND: The influence of genetics and environment on the association of the plasma proteome with body mass index (BMI) and changes in BMI remain underexplored, and the links to other omics in these associations remain to be investigated. We characterized protein-BMI trajectory associations in adolescents and adults and how these connect to other omics layers.METHODS: Our study included two cohorts of longitudinally followed twins: FinnTwin12 ( N =651) and the Netherlands Twin Register (NTR) ( N =665). Follow-up comprised four BMI measurements over approximately 6 (NTR: 23-27 years old) to 10 years (FinnTwin12: 12-22 years old), with omics data collected at the last BMI measurement. BMI changes were calculated using latent growth curve models. Mixed-effects models were used to quantify the associations between the abundance of 439 plasma proteins with BMI at blood sampling and changes in BMI. The sources of genetic and environmental variation underlying the protein abundances were quantified using twin models, as were the associations of proteins with BMI and BMI changes. In NTR, we investigated the association of gene expression of genes encoding proteins identified in FinnTwin12 with BMI and changes in BMI. We linked identified proteins and their coding genes to plasma metabolites and polygenic risk scores (PRS) using mixed-effect models and correlation networks.RESULTS: We identified 66 and 14 proteins associated with BMI at blood sampling and changes in BMI, respectively. The average heritability of these proteins was 35%. Of the 66 BMI-protein associations, 43 and 12 showed genetic and environmental correlations, respectively, including 8 proteins showing both. Similarly, we observed 6 and 4 genetic and environmental correlations between changes in BMI and protein abundance, respectively. S100A8 gene expression was associated with BMI at blood sampling, and the PRG4 and CFI genes were associated with BMI changes. Proteins showed strong connections with many metabolites and PRSs, but we observed no multi-omics connections among gene expression and other omics layers.CONCLUSIONS: Associations between the proteome and BMI trajectories are characterized by shared genetic, environmental, and metabolic etiologies. We observed few gene-protein pairs associated with BMI or changes in BMI at the proteome and transcriptome levels.PMID:37425750 | PMC:PMC10327285 | DOI:10.1101/2023.06.28.23291995

bioRxiv. 2023 Jun 3:2023.06.03.543565. doi: 10.1101/2023.06.03.543565. Preprint.ABSTRACTChagas Disease (CD), caused by Trypanosoma cruzi (T. cruzi) protozoa, is a complicated parasitic illness with inadequate medical measures for diagnosing infection and monitoring treatment success. To address this gap, we analyzed changes in the metabolome of T. cruzi-infected mice via liquid chromatography tandem mass spectrometry analysis of clinically-accessible biofluids: saliva, urine, and plasma. Urine was the most indicative of infection status, across mouse and parasite genotypes. Metabolites perturbed by infection in the urine include kynurenate, acylcarnitines, and threonylcarbamoyladenosine. Based on these results, we sought to implement urine as a tool for assessment of CD treatment success. Strikingly, it was found that mice with parasite clearance following benznidazole antiparasitic treatment had comparable overall urine metabolome to mice that failed to clear parasites. These results match with clinical trial data in which benznidazole treatment did not improve patient outcomes in late-stage disease. Overall, this study provides insights into new small molecule-based CD diagnostic methods and a new approach to assess functional treatment response.PMID:37425694 | PMC:PMC10326868 | DOI:10.1101/2023.06.03.543565

Bioinform Adv. 2023 Apr 21;3(1):vbad053. doi: 10.1093/bioadv/vbad053. eCollection 2023.ABSTRACTSUMMARY: Computational analysis and interpretation of metabolomic profiling data remains a major challenge in translational research. Exploring metabolic biomarkers and dysregulated metabolic pathways associated with a patient phenotype could offer new opportunities for targeted therapeutic intervention. Metabolite clustering based on structural similarity has the potential to uncover common underpinnings of biological processes. To address this need, we have developed the MetChem package. MetChem is a quick and simple tool that allows to classify metabolites in structurally related modules, thus revealing their functional information.AVAILABILITYAND IMPLEMENTATION: MetChem is freely available from the R archive CRAN (http://cran.r-project.org). The software is distributed under the GNU General Public License (version 3 or later).PMID:37424942 | PMC:PMC10322652 | DOI:10.1093/bioadv/vbad053

Front Endocrinol (Lausanne). 2023 Jun 22;14:1119599. doi: 10.3389/fendo.2023.1119599. eCollection 2023.ABSTRACTPURPOSE: Menopause is a risk factor for pelvic organ prolapse (POP) and is frequently associated with diminished vaginal wall support. To uncover relevant molecular mechanisms and provide potential therapeutic targets, we evaluated changes in the transcriptome and metabolome of the vaginal wall in ovariectomized rats to identify important molecular changes.METHODS: Sixteen adult female Sprague-Dawley rats were randomly assigned to either the control or menopause group. Seven months after the operation, hematoxylin and eosin (H&E) staining and Masson trichrome staining were used to observe changes in the rat vaginal wall structure. Differentially expressed genes (DEGs) and metabolites (DEMs) in the vaginal wall were detected by RNA-sequencing and LC-MS, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of DEGs and DEMs were performed.RESULTS: We verified that long-term menopause causes vaginal wall injury by H&E and Masson trichrome staining. From the multiomics analyses, 20,669 genes and 2193 metabolites were identified. Compared with the control group, 3255 DEGs were found in the vaginal wall of long-term menopausal rats. Bioinformatics analysis showed that the DEGs were mainly enriched in mechanistic pathways, including cell-cell junction, extracellular matrix, muscle tissue developments, the PI3K-Akt signaling pathway, the MAPK signaling pathway, tight junctions and the Wnt signaling pathway. Additionally, 313 DEMs were found, and they consisted mostly of amino acids and their metabolites. DEMs were also enriched in mechanistic pathways, such as glycine, serine and threonine metabolism, glycerophospholipid metabolism, gap junctions and ferroptosis. Coexpression analysis of DEGs and DEMs revealed that biosynthesis of amino acids (isocitric acid and PKM) and glycerophospholipid metabolism (1-(9Z-hexadecenoyl)-sn-glycero-3-phosphocholine and PGS1) are critical metabolic pathways, suggesting that POP induced by menopause may be associated with the regulation of these processes.CONCLUSION: The findings showed that long-term menopause greatly exacerbated vaginal wall support injury by decreasing the biosynthesis of amino acids and interfering with glycerophospholipid metabolism, which may result in POP. This study not only clarified that long-term menopause exacerbates damage to the vaginal wall but also provided insight into the potential molecular mechanisms by which long-term menopause induces POP.PMID:37424873 | PMC:PMC10324610 | DOI:10.3389/fendo.2023.1119599

MethodsX. 2023 Apr 25;10:102199. doi: 10.1016/j.mex.2023.102199. eCollection 2023.ABSTRACTThe Regions of Interest Multivariate curve Resolution (ROIMCR) methodology has gained significance for analyzing mass spectrometry data. The new SigSel package improves the ROIMCR methodology by providing a filtering step to reduce computational costs and to identify chemical compounds giving low-intensity signals. SigSel allows the visualization and assessment of ROIMCR results and filters out components resolved as interferences and background noise. This improves the analysis of complex mixtures and facilitates the identification of chemical compounds for statistical or chemometrics analysis. SigSel has been tested using metabolomics samples of mussels exposed to the sulfamethoxazole antibiotic. It begins by analyzing the data according to their charge state, eliminating signals considered background noise, and reducing the size of the datasets. In the ROIMCR analysis, the resolution of 30 ROIMCR components was achieved. After evaluating these components, 24 were ultimately selected explaining 99.05% of the total data variance. From ROIMCR results, chemical annotation is performed using different methods: •Generating a list of signals and reanalyzing them in a data-dependent analysis.•Comparing the ROIMCR resolved mass spectra to those stored in online repositories.•Searching MS signals of chemical compounds in the ROIMCR resolved spectra profiles.PMID:37424752 | PMC:PMC10326443 | DOI:10.1016/j.mex.2023.102199

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