PubMed

Pharmacotherapy. 2023 Sep 29. doi: 10.1002/phar.2884. Online ahead of print.ABSTRACTAIMS: The effects of the sodium-dependent glucose transporter-2 inhibitor ipragliflozin were compared with metformin in a previous study, which revealed that ipragliflozin reduced visceral fat content by 12%; however, the underlying mechanism was unclear. Therefore, this sub-analysis aimed to compare metabolomic changes associated with ipragliflozin and metformin that may contribute to their biological effects.MATERIALS AND METHODS: In the previous study, 103 patients with type 2 diabetes were randomly assigned to receive ipragliflozin 50 mg or metformin 1000 mg daily. Of the 103 patients, 15 patients in the ipragliflozin group with the highest reduction in visceral fat areas and 15 patients in the metformin group with matching characteristics, such as age, sex, baseline A1C, baseline visceral fat area, smoking status, and concomitant medication, were selected. The clinical data were reanalyzed, and metabolomic analysis of serum samples collected before and 24 weeks after drug administration was performed using capillary electrophoresis time-of-flight mass spectrometry.RESULTS: The reduction in the mean visceral fat area after 24 weeks of treatment was significantly larger (P=0.002) in the ipragliflozin group (-19.8%) than in the metformin group (-2.5%), as were the subcutaneous fat area and body weight. The A1C and blood glucose levels decreased in both groups. Glutamic pyruvic oxaloacetic transaminase, γ-glutamyl transferase, uric acid, and triglyceride levels decreased in the ipragliflozin group. Low-density lipoprotein cholesterol level decreased in the metformin group. After ipragliflozin administration, N2 -phenylacetylglutamine, inosine, guanosine, and 1-methyladenosine levels increased, whereas galactosamine, glucosamine, 11-aminoundecanoic acid, morpholine, and choline levels decreased. After metformin administration, metformin, hypotaurine, methionine, methyl-2-oxovaleric acid, 3-nitrotyrosine, and cyclohexylamine levels increased, whereas citrulline, octanoic acid, indole-3-acetaldehyde, and hexanoic acid levels decreased.CONCLUSIONS: Metabolites that may affect visceral fat reduction were detected in the ipragliflozin group. Studies are required to further elucidate the underlying mechanisms.PMID:37772313 | DOI:10.1002/phar.2884

Front Pediatr. 2023 Sep 12;11:1250731. doi: 10.3389/fped.2023.1250731. eCollection 2023.ABSTRACTBACKGROUND: Physical activity (PA) provides health benefits across the lifespan and improves many established cardiovascular risk factors that have a significant impact on overall mortality. However, discrepancies between self-reported and device-based measures of PA make it difficult to obtain consistent results regarding PA and its health effects. Moreover, PA may produce different health effects depending on the type, intensity, duration, and frequency of activities and individual factors such as age, sex, body weight, early life conditions/exposures, etc. Appropriate biomarkers relating the degree of PA level with its effects on health, especially in children and adolescents, are required and missing. The main objective of the INTEGRActiv study is to identify novel useful integrative biomarkers of PA and its effects on the body health in children and adolescents, who represent an important target population to address personalized interventions to improve future metabolic health.METHODS/DESIGN: The study is structured in two phases. First, biomarkers of PA and health will be identified at baseline in a core cohort of 180 volunteers, distributed into two age groups: prepubertal (n = 90), and postpubertal adolescents (n = 90). Each group will include three subgroups (n = 30) with subjects of normal weight, overweight, and obesity, respectively. Identification of new biomarkers will be achieved by combining physical measures (PA and cardiorespiratory and muscular fitness, anthropometry) and molecular measures (cardiovascular risk factors, endocrine markers, cytokines and circulating miRNA in plasma, gene expression profile in blood cells, and metabolomics profiling in plasma). In the second phase, an educational intervention and its follow-up will be carried out in a subgroup of these subjects (60 volunteers), as a first validation step of the identified biomarkers.DISCUSSION: The INTEGRActiv study is expected to provide the definition of PA and health-related biomarkers (PA-health biomarkers) in childhood and adolescence. It will allow us to relate biomarkers to factors such as age, sex, body weight, sleep behavior, dietary factors, and pubertal status and to identify how these factors quantitatively affect the biomarkers' responses. Taken together, the INTEGRActiv study approach is expected to help monitor the efficacy of interventions aimed to improve the quality of life of children/adolescents through physical activity.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, Identifier NCT05907785.PMID:37772038 | PMC:PMC10522911 | DOI:10.3389/fped.2023.1250731

Front Vet Sci. 2023 Sep 12;10:1281834. doi: 10.3389/fvets.2023.1281834. eCollection 2023.ABSTRACT[This corrects the article DOI: 10.3389/fvets.2021.687922.].PMID:37771944 | PMC:PMC10524247 | DOI:10.3389/fvets.2023.1281834

Chemometr Intell Lab Syst. 2023 Sep 15;240:104861. doi: 10.1016/j.chemolab.2023.104861. Epub 2023 Jun 1.ABSTRACTWe present metabolite identification software in the form of R Shiny. Metabolite identification by mass spectral matching in gas chromatography (GC-MS)-based untargeted metabolomics can be done by using the easy-to-use software. Various similarity measures are given and toy example using graphical user interface is presented.PMID:37771843 | PMC:PMC10538253 | DOI:10.1016/j.chemolab.2023.104861

Front Cell Infect Microbiol. 2023 Sep 12;13:1225991. doi: 10.3389/fcimb.2023.1225991. eCollection 2023.ABSTRACTBACKGROUND: Sarcopenia is a common complication in patients undergoing maintenance hemodialysis (MHD). Growing evidence suggests a close relationship between the gut microbiota and skeletal muscle. However, research on gut microbiota in patients with sarcopenia undergoing MHD (MS) remains scarce. To bridge this knowledge gap, we aimed to evaluate the pathogenic influence of gut microbiota in the skeletal muscle of patients with MS, to clarify the causal association between gut microbiota and skeletal muscle symptoms in patients with MS and identify the potential mechanisms underlying this causal association.METHODS: Fecal samples were collected from 10 patients with MS and 10 patients without MS (MNS). Bacteria were extracted from these samples for transplantation. Mice (n=42) were randomly divided into three groups and, after antibiotic treatment, fecal microbiota transplantation (FMT) was performed once a day for 3 weeks. Skeletal muscle and fecal samples from the mice were collected for 16S rRNA gene sequencing and for histological, real-time PCR, and metabolomic analyses.RESULTS: Mice colonized with gut microbiota from MS patients exhibited notable decreases in muscle function and muscle mass, compared with FMT from patients with MNS. Moreover, 16S rRNA sequencing revealed that the colonization of MS gut microbiota reduced the abundance of Akkermansia in the mouse intestines. Metabolome analysis revealed that seven metabolic pathways were notably disrupted in mice transplanted with MS microbiota.CONCLUSION: This study established a connection between skeletal muscle and the gut microbiota of patients with MS, implying that disruption of the gut microbiota may be a driving factor in the development of skeletal muscle disorders in patients undergoing MHD. This finding lays the foundation for understanding the pathogenesis and potential treatment methods for sarcopenia in patients undergoing MHD.PMID:37771694 | PMC:PMC10523162 | DOI:10.3389/fcimb.2023.1225991

Front Plant Sci. 2023 Sep 13;14:1244020. doi: 10.3389/fpls.2023.1244020. eCollection 2023.ABSTRACTLignin, a component of plant cell walls, possesses significant research potential as a renewable energy source to replace carbon-based products and as a notable pollutant in papermaking processes. The monolignol biosynthetic pathway has been elucidated and it is known that not all monolignol genes influence the total lignin content. However, it remains unclear which monolignol genes are more closely related to the total lignin content and which potential genes influence the total lignin content. In this study, we present a combination of t-test, differential gene expression analysis, correlation analysis, and weighted gene co-expression network analysis to identify genes that regulate the total lignin content by utilizing multi-omics data from transgenic knockdowns of the monolignol genes that includes data related to the transcriptome, proteome, and total lignin content. Firstly, it was discovered that enzymes from the PtrPAL, Ptr4CL, PtrC3H, and PtrC4H gene families are more strongly correlated with the total lignin content. Additionally, the co-downregulation of three genes, PtrC3H3, PtrC4H1, and PtrC4H2, had the greatest impact on the total lignin content. Secondly, GO and KEGG analysis of lignin-related modules revealed that the total lignin content is not only influenced by monolignol genes, but also closely related to genes involved in the "glutathione metabolic process", "cellular modified amino acid metabolic process" and "carbohydrate catabolic process" pathways. Finally, the cinnamyl alcohol dehydrogenase genes CAD1, CADL3, and CADL8 emerged as potential contributors to total lignin content. The genes HYR1 (UDP-glycosyltransferase superfamily protein) and UGT71B1 (UDP-glucosyltransferase), exhibiting a close relationship with coumarin, have the potential to influence total lignin content by regulating coumarin metabolism. Additionally, the monolignol genes PtrC3H3, PtrC4H1, and PtrC4H2, which belong to the cytochrome P450 genes, may have a significant impact on the total lignin content. Overall, this study establishes connections between gene expression levels and total lignin content, effectively identifying genes that have a significant impact on total lignin content and offering novel perspectives for future lignin research endeavours.PMID:37771490 | PMC:PMC10525687 | DOI:10.3389/fpls.2023.1244020

Front Plant Sci. 2023 Sep 12;14:1227507. doi: 10.3389/fpls.2023.1227507. eCollection 2023.ABSTRACTPinellia ternata (Thunb.) Breit. (Araceae), a significant medicinal plant, has been used to treat various diseases for centuries. Terahertz radiation (THZ) is located between microwaves and infrared rays on the electromagnetic spectrum. THZ possesses low single-photon energy and a spectral fingerprint, but its effects on plant growth have not yet been investigated. The study's primary objective was to examine the transcriptome and metabolome databases of the SY line to provide a new perspective for identifying genes associated with resistance and growth promotion and comprehending the underlying molecular mechanism. Variations in the biological characteristics of P. ternata grown under control and experimental conditions were analyzed to determine the effect of THZ. Compared with the control group, phenotypic variables such as leaf length, petiole length, number of leaves, leaf petiole diameter, and proliferation coefficient exhibited significant differences. P. ternata response to THZ was analyzed regarding the effects of various coercions on root exudation. The experimental group contained considerably more sugar alcohol than the control group. The transcriptome analysis revealed 1,695 differentially expressed genes (DEGs), including 509 upregulated and 1,186 downregulated genes. In the KEGG-enriched plant hormone signaling pathway, there were 19 differentially expressed genes, 13 of which were downregulated and six of which were upregulated. In the metabolomic analysis, approximately 416 metabolites were uncovered. There were 112 DEMs that were downregulated, whereas 148 were upregulated. The P. ternata leaves displayed significant differences in phytohormone metabolites, specifically in brassinolide (BR) and abscisic acid (ABA). The rise in BR triggers alterations in internal plant hormones, resulting in faster growth and development of P. ternata. Our findings demonstrated a link between THZ and several metabolic pathway processes, which will enhance our understanding of P. ternata mechanisms.PMID:37771489 | PMC:PMC10522861 | DOI:10.3389/fpls.2023.1227507

Front Plant Sci. 2023 Sep 12;14:1218594. doi: 10.3389/fpls.2023.1218594. eCollection 2023.ABSTRACTINTRODUCTION: Melilotus officinalis is a Leguminosae with relevant applications in medicine and soil recovery. This study reports the application of Melilotus officinalis plants in soil recovery and as a source of bioactive compounds.METHODS: Plants were cultivated in semiarid soil under four different fertilizer treatments, urban waste compost at 10 t/ha and 20 t/ha, inorganic fertilizer and a control (no fertilizer). Agronomic properties of soil (pH, EC, soil respiration, C content, macro- and microelements) were analyzed before and after treatment. Also, germination, biomass, element contents, and physiological response were evaluated. Metabolite composition of plants was analyzed through Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS).RESULTS AND DISCUSSION: Results showed a significant enhancement of the soil microbial activity in planted soils amended with compost, though there were no other clear effects on the soil physicochemical and chemical characteristics during the short experimental period. An improvement in M. officinalis germination and growth was observed in soils with compost amendment. Metabolite composition of plants was analyzed through Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Principal Component and Agglomerative Hierarchical Clustering models suggest that there is a clear separation of the metabolome of four groups of plants grown under different soil treatments. The five most important discriminative metabolites (annotated) were oleamide, palmitic acid, stearic acid, 3-hydroxy-cis-5-octenoylcarnitine, and 6-hydroxynon-7- enoylcarnitine. This study provides information on how the metabolome of Melilotus might be altered by fertilizer application in poor soil regions. These metabolome changes might have repercussions for the application of this plant in medicine and pharmacology. The results support the profitability of Melilotus officinalis cultivation for bioactive compounds production in association with soil recovery practices.PMID:37771488 | PMC:PMC10523325 | DOI:10.3389/fpls.2023.1218594

Front Plant Sci. 2023 Sep 13;14:1205725. doi: 10.3389/fpls.2023.1205725. eCollection 2023.ABSTRACTAntibacterial resistance poses a significant global threat, necessitating the discovery of new therapeutic agents. Plants are a valuable source of secondary metabolites with demonstrated anticancer and antibacterial properties. In this study, we reveal that Melastoma dodecandrum exhibits both bacteriostatic and bactericidal effects against Pseudomonas aeruginosa and Staphylococcus aureus. Treatment with plant extracts results in membrane damage and a reduction in P.aeruginosa swimming and swarming motility. A comparative analysis of bacterial transcriptomes exposed to M.dodecandrum extracts and four distinct antibiotics indicates that the extracts may trigger similar transcriptomic responses as triclosan, a fatty acid synthesis inhibitor. Activity-guided fractionation suggests that the antibacterial activity is not attributable to hydrolyzable tannins, but to unidentified minor compounds. Additionally, we identified 104 specialized metabolic pathways and demonstrated a high level of transcriptional coordination between these biosynthetic pathways and phytohormones, highlighting potential regulatory mechanisms of antibacterial metabolites in M.dodecandrum.PMID:37771487 | PMC:PMC10525717 | DOI:10.3389/fpls.2023.1205725

Front Oncol. 2023 Sep 12;13:1190706. doi: 10.3389/fonc.2023.1190706. eCollection 2023.ABSTRACTOBJECTIVE: To profile the serum metabolites and metabolic pathways in colorectal cancer (CRC) patients associated with spleen-deficiency and qi-stagnation syndrome (SDQSS) or damp-heat syndrome (DHS).METHODS: From May 2020 to January 2021, CRC patients diagnosed with traditional Chinese medicine (TCM) syndromes of SDQSS or DHS were enrolled. The clinicopathological data of the SDQSS and DHS groups were compared. The serum samples were analyzed by liquid chromatography-mass spectrometry (LC-MS). The variable importance in the projection >1, fold change ≥3 or ≤0.333, and P value ≤0.05 were used to identify differential metabolites between the two groups. Furthermore, areas under the receiver operating characteristic (ROC) curve > 0.9 were applied to select biomarkers with good predictive performance. The enrichment metabolic pathways were searched through the database of Kyoto Encyclopedia of Genes and Genomes.RESULTS: 60 CRC patients were included (30 SDQSS and 30 DHS). The level of alanine aminotransferase was marginally significantly higher in the DHS group than the SDQSS group (P = 0.051). The other baseline clinicopathological characteristics were all comparable between the two groups. 23 differential serum metabolites were identified, among which 16 were significantly up-regulated and 7 were significantly down-regulated in the SDQSS group compared with the DHS group. ROC curve analysis showed that (S)-3-methyl-2-oxopentanoic acid, neocembrene, 1-aminocyclopropanecarboxylic acid, 3-methyl-3-hydroxypentanedioate, and nicotine were symbolic differential metabolites with higher predictive power. The top five enrichment signalling pathways were valine, leucine and isoleucine biosynthesis; lysosome; nicotine addiction; fructose and mannose metabolism; and pertussis.CONCLUSION: Our study identifies the differential metabolites and characteristic metabolic pathways among CRC patients with SDQSS or DHS, offering the possibility of accurate and objective syndrome differentiation and TCM treatment for CRC patients.PMID:37771438 | PMC:PMC10523394 | DOI:10.3389/fonc.2023.1190706

J Mol Cell Biol. 2023 Sep 28:mjad060. doi: 10.1093/jmcb/mjad060. Online ahead of print.ABSTRACTNon-alcoholic steatohepatitis (NASH) is a condition that progresses from non-alcoholic fatty liver disease (NAFLD) and is characterized by hepatic fat accumulation, inflammation, and fibrosis. It has the potential to lead to cirrhosis and liver cancer, with currently no effective pharmacological treatment available. In this study, we investigate the therapeutic potential of targeting ceruloplasmin (Cp), a copper-containing protein predominantly secreted by hepatocytes, for treating NASH. Our result show that hepatic Cp was remarkedly upregulated in individuals with NASH and the mouse NASH model. Hepatocyte-specific Cp ablation effectively attenuates the onset of dietary-induced NASH by decreasing lipid accumulation, curbing inflammation, mitigating fibrosis and ameliorating liver damage. By employing transcriptomics and metabolomics approaches, we have discovered that hepatic deletion of Cp brings about the remarkable restoration of NASH by profoundly influencing bile acid metabolism. Hepatic deletion of Cp effectively remodels bile acid metabolism by upregulating Cyp7a1 and Cyp8b1, which subsequently leads to enhanced bile acid synthesis and notable alterations in bile acid profiles. In conclusion, our studies elucidate the crucial involvement of Cp in NASH, highlighting its significance as a promising therapeutic target for the treatment of this disease.PMID:37771074 | DOI:10.1093/jmcb/mjad060

Brief Bioinform. 2023 Sep 22;24(6):bbad325. doi: 10.1093/bib/bbad325.ABSTRACTA microbial community maintains its ecological dynamics via metabolite crosstalk. Hence, knowledge of the metabolome, alongside its populace, would help us understand the functionality of a community and also predict how it will change in atypical conditions. Methods that employ low-cost metagenomic sequencing data can predict the metabolic potential of a community, that is, its ability to produce or utilize specific metabolites. These, in turn, can potentially serve as markers of biochemical pathways that are associated with different communities. We developed MMIP (Microbiome Metabolome Integration Platform), a web-based analytical and predictive tool that can be used to compare the taxonomic content, diversity variation and the metabolic potential between two sets of microbial communities from targeted amplicon sequencing data. MMIP is capable of highlighting statistically significant taxonomic, enzymatic and metabolic attributes as well as learning-based features associated with one group in comparison with another. Furthermore, MMIP can predict linkages among species or groups of microbes in the community, specific enzyme profiles, compounds or metabolites associated with such a group of organisms. With MMIP, we aim to provide a user-friendly, online web server for performing key microbiome-associated analyses of targeted amplicon sequencing data, predicting metabolite signature, and using learning-based linkage analysis, without the need for initial metabolomic analysis, and thereby helping in hypothesis generation.PMID:37771003 | DOI:10.1093/bib/bbad325

Mutat Res Genet Toxicol Environ Mutagen. 2023 Oct;891:503681. doi: 10.1016/j.mrgentox.2023.503681. Epub 2023 Aug 18.ABSTRACTGenotoxicity is an important information that should be included in human biomonitoring programmes. However, the usually applied cytogenetic assays are laborious and time-consuming, reason why it is critical to develop rapid and economic new methods. The aim of this study was to evaluate if the molecular profile of frozen whole blood, acquired by Fourier Transform Infrared (FTIR) spectroscopy, allows to assess genotoxicity in occupational exposure to antineoplastic drugs, as obtained by the cytokinesis-block micronucleus assay. For that purpose, 92 samples of peripheral blood were studied: 46 samples from hospital professionals occupationally exposed to antineoplastic drugs and 46 samples from workers in academia without exposure (controls). It was first evaluated the metabolome from frozen whole blood by methanol precipitation of macromolecules as haemoglobin, followed by centrifugation. The metabolome molecular profile resulted in 3 ratios of spectral bands, significantly different between the exposed and non-exposed group (p < 0.01) and a spectral principal component-linear discriminant analysis (PCA-LDA) model enabling to predict genotoxicity from exposure with 73 % accuracy. After optimization of the dilution degree and solution used, it was possible to obtain a higher number of significant ratios of spectral bands, i.e., 10 ratios significantly different (p < 0.001), highlighting the high sensitivity and specificity of the method. Indeed, the PCA-LDA model, based on the molecular profile of whole blood, enabled to predict genotoxicity from the exposure with an accuracy, sensitivity, and specificity of 92 %, 93 % and 91 %, respectively. All these parameters were achieved based on 1 μL of frozen whole blood, in a high-throughput mode, i.e., based on the simultaneous analysis of 92 samples, in a simple and economic mode. In summary, it can be conclude that this method presents a very promising potential for high-dimension screening of exposure to genotoxic substances.PMID:37770138 | DOI:10.1016/j.mrgentox.2023.503681

Plant Physiol. 2023 Sep 28:kiad515. doi: 10.1093/plphys/kiad515. Online ahead of print.ABSTRACTTandem direct repeat (TDR)-containing proteins, present across all domains of life, play crucial roles in plant development and defense mechanisms. Previously, we identified that disruption of a bryophyte-specific protein family, SHORT-LEAF (SHLF), possessing the longest reported TDRs, is the cause of the shlf mutant phenotype in Physcomitrium patens. shlf exhibits reduced apical dominance, altered auxin distribution, and two-fold shorter leaves. However, the molecular role of SHLF was unclear due to the absence of known conserved domains. Through a series of protein domain deletion analyses, here, we demonstrate the importance of the signal peptide and the conserved TDRs and report a minimal functional protein (miniSHLF) containing the N-terminal signal peptide and first two TDRs (N-TDR1-2). We also demonstrate that SHLF behaves as a secretory protein and that the TDRs contribute to a pool of secreted peptides essential for SHLF function. Further, we identified that the mutant secretome lacks SHLF peptides, which are abundant in WT and miniSHLF secretomes. Interestingly, shlf mutants supplemented with the secretome or peptidome from WT or miniSHLF showed complete or partial phenotypic recovery. Transcriptomic and metabolomic analyses revealed that shlf displays an elevated stress response, including high ROS activity and differential accumulation of genes and metabolites involved in the phenylpropanoid pathway, which may affect auxin distribution. The TDR-specific synthetic peptide SHLFpep3 (INIINAPLQGFKIA) also rescued the mutant phenotypes, including the altered auxin distribution, in a dosage-dependent manner and restored the mutant's stress levels. Our study shows that secretory SHLF peptides derived from conserved TDRs regulate moss gametophore development.PMID:37770073 | DOI:10.1093/plphys/kiad515

Life Sci. 2023 Sep 26:122125. doi: 10.1016/j.lfs.2023.122125. Online ahead of print.ABSTRACTSarcopenia remains one of the major pathological features of type 2 diabetes (T2D), especially in older individuals. This condition describes gradual loss of muscle mass, strength, and function that reduces the overall vitality and fitness, leading to increased hospitalizations and even fatalities to those affected. Preclinical evidence indicates that dysregulated mitochondrial dynamics, together with impaired activity of the NADPH oxidase system, are the major sources of oxidative stress that drive skeletal muscle damage in T2D. While patients with T2D also display relatively higher levels of circulating inflammatory markers in the serum, including high sensitivity-C-reactive protein, interleukin-6, and tumor necrosis factor-α that are independently linked with the deterioration of muscle function and sarcopenia in T2D. In fact, beyond reporting on the pathological consequences of both oxidative stress and inflammation, the current review highlights the importance of strengthening intracellular antioxidant systems to preserve muscle mass, strength, and function in individuals with T2D.PMID:37769808 | DOI:10.1016/j.lfs.2023.122125

Neurobiol Dis. 2023 Sep 26:106312. doi: 10.1016/j.nbd.2023.106312. Online ahead of print.ABSTRACTAlzheimer's disease is the most common type of dementia in the elderly. It is a progressive degenerative disorder that may begin to develop up to 15 years before clinical symptoms appear. The identification of early biomarkers is crucial to enable a prompt diagnosis and to start effective interventions. In this work, we conducted a metabolomic study using proton Nuclear Magnetic Resonance (1H NMR) spectroscopy in serum samples from patients with neuropathologically confirmed Alzheimer's disease (AD, n = 51), mild cognitive impairment (MCI, n = 27), and cognitively healthy controls (HC, n = 50) to search for metabolites that could be used as biomarkers. Patients and controls underwent yearly clinical follow-ups for up to six years. MCI group included samples from three subgroups of subjects with different disease progression rates. The first subgroup included subjects that remained clinically stable at the MCI stage during the period of study (stable MCI, S-MCI, n = 9). The second subgroup accounted for subjects which were diagnosed with MCI at the moment of blood extraction, but progressed to clinical dementia in subsequent years (MCI-to-dementia, MCI-D, n = 14). The last subgroup was composed of subjects that had been diagnosed as dementia for the first time at the moment of sample collection (incipient dementia, Incp-D, n = 4). Partial Least Square Discriminant Analysis (PLS-DA) models were developed. Three models were obtained, one to discriminate between AD and HC samples with high sensitivity (93.75%) and specificity (94.75%), another model to discriminate between AD and MCI samples (100% sensitivity and 82.35% specificity), and a last model to discriminate HC and MCI with lower sensitivity and specificity (67% and 50%). Differences within the MCI group were further studied in an attempt to determine those MCI subjects that could develop AD-type dementia in the future. The relative concentration of metabolites, and metabolic pathways were studied. Alterations in the pathways of alanine, aspartate and glutamate metabolism, pantothenate and CoA biosynthesis, and beta-alanine metabolism, were found when HC and MCI- D patients were compared. In contrast, no pathway was found disturbed in the comparison of S-MCI with HC groups. These results highlight the potential of 1H NMR metabolomics to support the diagnosis of dementia in a less invasive way, and set a starting point for the study of potential biomarkers to identify MCI or HC subjects at risk of developing AD in the future.PMID:37769747 | DOI:10.1016/j.nbd.2023.106312

Sci Total Environ. 2023 Sep 26:167352. doi: 10.1016/j.scitotenv.2023.167352. Online ahead of print.ABSTRACTWide usage of plastic coupled with mismanagement has created a humongous environmental hazard threatening entire ecosystems. To date, the potential effects of plastic debris-induced soil nutrition substance changes and the relevant microbial metabolic behavior remain unclear. Here, we studied the effect of plastic films polyethylene and polylactic acid in differential soil environments (farmland, woodland, and wetland) for 120 days. Soil enzyme activities (urease, neutral phosphatase, and catalase) and nutrition substance (NH4+-N, available P, available K, and soil organic matter) present obvious variations in polylactic acid groups compared to polyethylene-treated samples. 16S rRNA gene sequencing indicates that several bacteria abundance such as Bacteroidales, Actinobacteriota, Nitrososphaeraceae, Pyrinomonadalcs, Muribaculaceae, exhibited obvious up-regulation or down-regulation, and simultaneously, the carbon, nitrogen, and phosphorus cycling relevant species Bryobacter, Bradyrhizobium, and Sphingomonas, expressed wider margin of down-regulation in abundance in plastic treatment soil samples. As a result, the abundance of metabolites including sugar, amino acid, and fatty acids, which may associated with nutrition substance metabolic pathways, were significantly altered in the stress of plastic. These findings provide valuable information on the environmental effects of plastics, and the relationships of subsequent nutrition substance changes and microbial metabolic behavior.PMID:37769723 | DOI:10.1016/j.scitotenv.2023.167352

Sci Total Environ. 2023 Sep 26:167359. doi: 10.1016/j.scitotenv.2023.167359. Online ahead of print.ABSTRACTThe co-existence of microplastics (MPs) and antibiotics in the coastal environment poses a combined ecological risk. Single toxic effects of MPs or antibiotics on aquatic organisms have been verified, however, the exploration of their combined toxic effects remains limited. Here, foodborne polystyrene microplastics (PS-MPs, 10 μm, 0.1 % w/w in food) and waterborne tetracyclines (TC, 50 μg/L) were used to expose an estuarine fish Oryzias melastigma for four weeks. We found that the aqueous availability of TC was not significantly altered coexisting with MPs. The fish body weight gain was significantly slower in TC alone or combined groups than the control group, consistent with the lower lipid content in livers. The body length gain was significantly inhibited by the combined presence compared to the single exposure. Both exposures led to a shift of gut microbiota composition and diversity. TC and the combined group possessed similar gut microbiota which is distinct from PS-MPs and the control group. The Firmicutes/Bacteroidetes (F/B) ratio in the TC and combined groups were significantly lower compared to the control, while the PS-MPs group showed no significant impact. Metabolomic analysis of the fish liver confirmed the shift of metabolites in specific pathways after different exposures. More, a number of gut microbiota-related metabolites on lipid metabolism was perturbed, which were annotated in arachidonic acid metabolism and linoleic acid metabolism. In all, TC modulates bacterial composition in the fish gut and disturbs their liver metabolites via the gut-liver axis, which led to the slower growth of O. melastigma. More, the adverse impact was aggravated by the co-exposure to foodborne PS-MPs.PMID:37769716 | DOI:10.1016/j.scitotenv.2023.167359

J Clin Endocrinol Metab. 2023 Sep 28:dgad559. doi: 10.1210/clinem/dgad559. Online ahead of print.ABSTRACTOBJECTIVES: To describe cerebrospinal fluid (CSF) metabolomic pattern of pituitary stalk lesions.METHODS: CSF was collected from patients with different pituitary stalk lesions (germ cell tumor (GCT), n = 27; hypophysitis, n = 10; Langerhans cell histiocytosis (LCH) or Erdheim-Chester disease (ECD), n = 10) treated at Peking Union Medical College Hospital. CSF metabolome profiling was characterized through Liquid Chromatography-Mass Spectrometer (LC-MS).RESULTS: 44 metabolites were significantly different between GCT and hypophysitis patients (P < 0.05). When comparing GCT (CSF beta subunit of human chorionic gonadotrophin (β-hCG) < 5 mIU/ml) with hypophysitis patients, there were 15 differential metabolites (P < 0.05, fold change > 1.5 or < 1/1.5). All the metabolites had the AUC (area under the curve) above 0.7. Besides, 9 metabolites were significantly different between GCT and LCH + ECD patients (P < 0.05) and 7 metabolites had significant differences between GCT (CSF β-hCG < 5 mIU/ml) and LCH + ECD patients (P < 0.05, fold change > 1.5 or < 1/1.5). 6 metabolites were significantly different between hypophysitis and LCH + ECD patients (P < 0.05) and 5 of them had fold change more than 1.5 or less than 1/1.5. Three metabolites, 5-deoxydiplosporin, cloversaponin I and phytosphingosine, showed excellent capabilities to differentiate three diseases. Furthermore, we determined 67 metabolites associated with clinical test results (ρ > 0.2, P < 0.05) and 29 metabolites showed strong correlation (ρ > 0.4, P < 0.05).CONCLUSIONS: Our study is the first to systematically investigate the metabolomics of CSF in different pituitary stalk lesions. CSF metabolomics is a useful strategy for biomarker discovery.PMID:37769631 | DOI:10.1210/clinem/dgad559

Food Chem. 2023 Sep 22;435:137529. doi: 10.1016/j.foodchem.2023.137529. Online ahead of print.ABSTRACTThe production of fine-flavor cocoa represents a promising avenue to enhance socioeconomic development in Colombia and Latin America. Premium chocolate is obtained through a post-harvesting process, which relies on semi-standardized techniques. The change in the metabolic profile during cocoa processing considerably impacts flavor and nutraceutical properties of the final product. Understanding this impact considering both volatiles and non-volatile compounds is crucial for process and product re-engineering of cocoa post-harvesting. Consequently, this work studied the metabolic composition of cocoa liquor by untargeted metabolomics and lipidomics. This approach offered a comprehensive view of cocoa biochemistry, considering compounds associated with bioactivity and flavor in cocoa liquor. Their variations were traced back over the cocoa processing (i.e., drying, and roasting), highlighting their impact on flavor development and the nutraceutical properties. These results represent the basis for future studies aimed to re-engineer cocoa post-harvesting considering the variation of key flavor and bioactive compounds over processing.PMID:37769563 | DOI:10.1016/j.foodchem.2023.137529