PubMed

Front Immunol. 2024 Sep 27;15:1469500. doi: 10.3389/fimmu.2024.1469500. eCollection 2024.ABSTRACTINTRODUCTION: Kidney transplantation is the optimal treatment for end-stage kidney disease; however, premature allograft loss remains a serious issue. While many high-throughput omics studies have analyzed patient allograft biospecimens, integration of these datasets is challenging, which represents a considerable barrier to advancing our understanding of the mechanisms of allograft loss.METHODS: To facilitate integration, we have created a curated database containing all open-access high-throughput datasets from human kidney transplant studies, termed NephroDIP (Nephrology Data Integration Portal). PubMed was searched for high-throughput transcriptomic, proteomic, single nucleotide variant, metabolomic, and epigenomic studies in kidney transplantation, which yielded 9,964 studies.RESULTS: From these, 134 studies with available data detailing 260 comparisons and 83,262 molecules were included in NephroDIP v1.0. To illustrate the capabilities of NephroDIP, we have used the database to identify common gene, protein, and microRNA networks that are disrupted in patients with chronic antibody-mediated rejection, the most important cause of late allograft loss. We have also explored the role of an immunomodulatory protein galectin-1 (LGALS1), along with its interactors and transcriptional regulators, in kidney allograft injury. We highlight the pathways enriched among LGALS1 interactors and transcriptional regulators in kidney fibrosis and during immunosuppression.DISCUSSION: NephroDIP is an open access data portal that facilitates data visualization and will help provide new insights into existing kidney transplant data through integration of distinct studies and modules (https://ophid.utoronto.ca/NephroDIP).PMID:39399491 | PMC:PMC11466753 | DOI:10.3389/fimmu.2024.1469500

FASEB Bioadv. 2024 Aug 19;6(9):337-350. doi: 10.1096/fba.2024-00060. eCollection 2024 Sep.ABSTRACTStimulation of mammalian cells with inflammatory inducers such as lipopolysaccharide (LPS) leads to alterations in activity of central cellular metabolic pathways. Interestingly, these metabolic changes seem to be important for subsequent release of pro-inflammatory cytokines. This has become particularly clear for enzymes of tricarboxylic acid (TCA) cycle such as succinate dehydrogenase (SDH). LPS leads to inhibition of SDH activity and accumulation of succinate to enhance the LPS-induced formation of IL-1β. If enzymes involved in beta-oxidation of fatty acids are important for sufficient responses to LPS is currently not clear. Using cells from various patients with inborn long-chain fatty acid oxidation disorders (lcFAOD), we report that disease-causing deleterious variants of Electron Transfer Flavoprotein Dehydrogenase (ETFDH) and of Very Long Chain Acyl-CoA Dehydrogenase (ACADVL), both cause insufficient inflammatory responses to stimulation with LPS. The insufficiencies included reduced TLR4 expression levels, impaired TLR4 signaling, and reduced or absent induction of pro-inflammatory cytokines such as IL-6. The insufficient responses to LPS were reproduced in cells from healthy controls by targeted loss-of-function of either ETFDH or ACADVL, supporting that the deleterious ETFDH and ACADVL variants cause the attenuated responses to LPS. ETFDH and ACADVL encode two distinct enzymes both involved in fatty acid beta-oxidation, and patients with these deficiencies cannot sufficiently metabolize long-chain fatty acids. We report that genes important for beta-oxidation of long-chain fatty acids are also important for inflammatory responses to an acute immunogen trigger like LPS, which may have important implications for understanding infection and other metabolic stress induced disease pathology in lcFAODs.PMID:39399475 | PMC:PMC11467727 | DOI:10.1096/fba.2024-00060

PeerJ. 2024 Oct 8;12:e18194. doi: 10.7717/peerj.18194. eCollection 2024.ABSTRACTBACKGROUND: Polycystic ovary syndrome (PCOS) is the most common metabolic disorder and reproductive endocrine disease, posing an elevated risk to women of reproductive age. Although metabolism differences in serum, amniotic fluid and urine have been documented in PCOS, there remains a paucity of evidence for vaginal fluid. This study aimed to identify the metabolic characteristics and potential biomarkers of PCOS in Chinese women of reproductive age.METHODS: We involved ten newly diagnosed PCOS women who attended gynecology at Zhongda Hospital and matched them with ten healthy controls who conducted health check-up programs at Gulou Maternal and Child Health Center in Nanjing, China from January 1st, 2019 to July 31st, 2020. Non-targeted metabolomics based on ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was applied to differentially screen vaginal metabolites between PCOS group and healthy controls. Principal component analysis (PCA), orthogonal partial least-squares discriminant analysis (OPLS-DA) and enrichment analysis were used to observe differences, search for potential biomarkers and enrich related pathways.RESULTS: Among the 20 participants, a total of 195 different metabolites were detected between PCOS group and healthy control group. PCOS and control groups were effectively separated by vaginal fluid. Lipids and lipid-like molecules constituted the majority of differential metabolites. Notably, dopamine exhibited an increased trend in PCOS group and emerged as the most significant differential metabolite, suggesting its potential as a biomarker for identifying PCOS. The application of UHPLC-MS/MS based vaginal metabolomics methods showed significant differences between PCOS and non-PCOS healthy control groups, especially linoleic acid metabolism disorder. Most differential metabolites were enriched in pathways associated with linoleic acid metabolism, phenylalanine metabolism, tyrosine metabolism, nicotinate and nicotinamide metabolism or arachidonic acid metabolism.CONCLUSIONS: In this pilot investigation, significant metabolomics differences could be obtained between PCOS and healthy control groups. For PCOS women of reproductive age, vaginal metabolism is a more economical, convenient and harmless alternative to provide careful personalized health diagnosis and potential targets for therapeutic intervention.PMID:39399434 | PMC:PMC11468964 | DOI:10.7717/peerj.18194

One Health. 2024 Sep 24;19:100902. doi: 10.1016/j.onehlt.2024.100902. eCollection 2024 Dec.ABSTRACTTo provide some glimpses on the possibility of shaping the human gut microbiome (GM) through probiotic exchange with natural ecosystems, here we explored the impact of 15 days of daily interaction with horses on the GM of 10 urban-living Italian children. Specifically, the children were in close contact with the horses in an "educational farm", where they spent almost 10 h/day interacting with the animals. The children's GM was assessed before and after the horse interaction using metabarcoding sequencing and shotgun metagenomics, along with the horses' skin, oral and fecal microbiomes. Targeted metabolomic analysis for GM-produced beneficial metabolites (i.e., short-chain fatty acids) in the children's feces was also performed. Interaction with horses facilitated the acquisition of health-related traits in the children's GM, such as increased diversity, enhanced butyrate production and an increase in several health-promoting species considered to be next-generation probiotics. Among these, the butyrate producers Facecalibacterium prausnitzii and F. duncaniae and a species belonging to the order Christensenellales. Interaction with horses was also associated with increased proportions of Eggerthella lenta, Gordonibacter pamelae and G. urolithinfaciens, GM components known to play a role in the bioconversion of dietary plant polyphenols into beneficial metabolites. Notably, no increase in potentially harmful traits, including toxin genes, was observed. Overall, our pilot study provides some insights on the existence of possible health-promoting exchanges between children and horses microbiomes. It lays the groundwork for an implemented and more systematic enrollment effort to explore the full complexity of human GM rewilding through exchange with natural ecosystems, aligning with the One Health approach.PMID:39399231 | PMC:PMC11470462 | DOI:10.1016/j.onehlt.2024.100902

Drug Des Devel Ther. 2024 Oct 9;18:4527-4528. doi: 10.2147/DDDT.S497570. eCollection 2024.NO ABSTRACTPMID:39399127 | PMC:PMC11471113 | DOI:10.2147/DDDT.S497570

medRxiv [Preprint]. 2024 Sep 24:2024.09.24.24313672. doi: 10.1101/2024.09.24.24313672.ABSTRACTInflammation is a critical component of chronic diseases, aging progression, and lifespan. Omics signatures may characterize inflammation status beyond blood biomarkers. We leveraged genetics (Polygenic-Risk-Score; PRS), metabolomics (Metabolomic-Risk-Score; MRS), and epigenetics (Epigenetic-Risk-Score; ERS) to build multi-omics-multi-marker risk scores for inflammation status represented by the level of circulating C-reactive protein (CRP), interleukin 6 (IL6), and tumor necrosis factor alpha (TNFa). We found that multi-omics risk-scores generally outperformed single-omics risk scores in prediction of all-cause mortality in the Canadian Longitudinal Study on Aging. Compared with circulating inflammation biomarkers, some multi-omics risk scores had a higher HR for all cause-mortality when including both score and circulating IL6 in the same model (1-SD IL6 MRS-ERS: HR=1.77 [1.15-2.72] vs. 1-SD circulating IL6 HR=1.11 [0.75,1.66]; 1-SD IL6 PRS-MRS: HR=1.32 [1.21,1.45] vs. 1-SD circulating IL6 HR=1.31 [1.12, 1.53]; 1-SD PRS-MRS-ERS: HR=1.62 [1.04, 2.53] vs. 1-SD circulating IL6: HR=1.16 [0.77, 1.74]). In the Nurses' Health Study (NHS), NHS II, and Health Professional Follow-up Study with available omics, 1-SD of IL6 PRS and 1-SD IL6 PRS-MRS had HR=1.13 [1.00,1.27] and HR=1.13 [1.01,1.27], among individuals >65years without mutual adjustment of the score and circulating IL6. Our study demonstrated that some multi-omics scores for inflammation markers may characterize important inflammation burden for an individual beyond those represented by blood biomarkers and improve our prediction capability for aging process and lifespan.PMID:39399025 | PMC:PMC11469340 | DOI:10.1101/2024.09.24.24313672

Food Chem X. 2024 Sep 21;24:101851. doi: 10.1016/j.fochx.2024.101851. eCollection 2024 Dec 30.ABSTRACTShengmuxiang (SMX), an important aroma in Jiang-flavor base baijiu, significantly influences the quality of the product. This study employed untargeted metabolomics combined with sensomics to explore the key compounds responsible for SMX. Results indicated that SMX samples had higher intensities of green and woody-like odors compare to control samples. A total of 87 aroma compounds were identified by headspace solid phase microextraction combined with gas chromatography-mass spectrometry technology. Based on the variable projection importance, PCA and OPLS-DA were employed to identify 22 potential marker compounds. Quantitative results combined with hierarchical cluster and OAV analysis revealed that 9 aroma compounds (OAV > 1) had high concentrations in SMX samples. Aroma recombination and omission experiments further indicated that acetaldehyde and acetal were the key compounds responsible for the characteristic aroma of SMX in Jiang-flavor base baijiu. These findings provide valuable insights into the distinct aroma profile of SMX and offer a basis for quality control of Jiang-flavor base baijiu.PMID:39398868 | PMC:PMC11470176 | DOI:10.1016/j.fochx.2024.101851

Phenomics. 2024 Mar 10;4(3):227-233. doi: 10.1007/s43657-023-00123-z. eCollection 2024 Jun.ABSTRACTThis research was to reveal the key factors in the progression of osteoarthritis (OA) using non-targeted metabolomics and to find targeted therapies for patients with OA. Twenty-two patients with knee OA scheduled for total knee arthroplasty were divided into two groups: Kellgren-Lawrence (KL) grade 3 (n = 16) and grade 4 (n = 6), according to plain X-rays of the knee. After the operation, the cartilages of femur samples were analyzed using non-targeted metabolomics. When compared with grade 3 patients, the levels of choline, 2-propylpiperidine, rhamnose, and monomethyl glutaric acid were higher; while 1-methylhistamine, sphingomyelin (SM) (d18:1/14:0), zeranol, 3- (4-hydroxyphenyl)-1-propanol, 5-aminopentanamide, dihydrouracil, 2-hydroxypyridine, and 3-amino-2-piperidone were lower in grade 4 patients. Furthermore, some metabolic pathways were found to be significantly different in two groups such as the pantothenate and coenzyme A (CoA) biosynthesis pathway, the glycerophospholipid metabolism pathway, histidine metabolism pathway, lysine degradation pathway, glycine, serine and threonine metabolism pathway, fructose and mannose metabolism pathway, the pyrimidine metabolism pathway, and beta-alanine metabolism pathway. This work used non-targeted metabolomics and screened out differential metabolites and metabolic pathways, providing a reliable theoretical basis for further study of specific markers and their specific pathways in the progression of OA.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43657-023-00123-z.PMID:39398425 | PMC:PMC11466919 | DOI:10.1007/s43657-023-00123-z

Anal Chem. 2024 Oct 14. doi: 10.1021/acs.analchem.4c03724. Online ahead of print.ABSTRACTA pivotal challenge in metabolite research is the structural annotation of metabolites from tandem mass spectrometry (MS/MS) data. The integration of artificial intelligence (AI) has revolutionized the interpretation of MS data, facilitating the identification of elusive metabolites within the metabolomics landscape. Innovative methodologies are primarily focusing on transforming MS/MS spectra or molecular structures into a unified modality to enable similarity-based comparison and interpretation. In this work, we present CMSSP, a novel Contrastive Mass Spectra-Structure Pretraining framework designed for metabolite annotation. The primary objective of CMSSP is to establish a representation space that facilitates a direct comparison between MS/MS spectra and molecular structures, transcending the limitations of distinct modalities. The evaluation on two benchmark test sets demonstrates the efficacy of the approach. CMSSP achieved a remarkable enhancement in annotation accuracy, outperforming the state-of-the-art methods by a significant margin. Specifically, it improved the top-1 accuracy by 30% on the CASMI 2017 data set and realized a 16% increase in top-10 accuracy on an independent test set. Moreover, the model displayed superior identification accuracy across all seven chemical categories, showcasing its robustness and versatility. Finally, the MS/MS data of 30 metabolites from Glycyrrhiza glabra were analyzed, achieving top-1 and top-3 accuracies of 86.7 and 100%, respectively. The CMSSP model serves as a potent tool for the dissection and interpretation of intricate MS/MS data, propelling the field toward more accurate and efficient metabolite annotation. This not only augments the analytical capabilities of metabolomics but also paves the way for future discoveries in understanding of complex biological systems.PMID:39397774 | DOI:10.1021/acs.analchem.4c03724

Gut Microbes. 2024 Jan-Dec;16(1):2412669. doi: 10.1080/19490976.2024.2412669. Epub 2024 Oct 14.ABSTRACTGut microbiota-derived metabolites play a pivotal role in the maintenance of intestinal immune homeostasis. Here, we demonstrate that the human commensal Clostridium sporogenes possesses a specific metabolic fingerprint, consisting predominantly of the tryptophan catabolite indole-3-propionic acid (IPA), the branched-chain acids (BCFAs) isobutyrate and isovalerate and the short-chain fatty acids (SCFAs) acetate and propionate. Mono-colonization of germ-free mice with C. sporogenes (CS mice) affected colonic mucosal immune cell phenotypes, including up-regulation of Il22 gene expression, and increased abundance of transcriptionally active colonic tuft cells and Foxp3+ regulatory T cells (Tregs). In DSS-induced colitis, conventional mice suffered severe inflammation accompanied by loss of colonic crypts. These symptoms were absent in CS mice. In conventional, but not CS mice, bulk RNAseq analysis of the colon revealed an increase in inflammatory and Th17-related gene signatures. C. sporogenes-derived IPA reduced IL-17A protein expression by suppressing mTOR activity and by altering ribosome-related pathways in Th17 cells. Additionally, BCFAs and SCFAs generated by C. sporogenes enhanced the activity of Tregs and increased the production of IL-22, which led to protection from colitis. Collectively, we identified C. sporogenes as a therapeutically relevant probiotic bacterium that might be employed in patients with inflammatory bowel disease (IBD).PMID:39397690 | DOI:10.1080/19490976.2024.2412669

Brief Bioinform. 2024 Sep 23;25(6):bbae498. doi: 10.1093/bib/bbae498.ABSTRACTMetabolite profiling is a powerful approach for the clinical diagnosis of complex diseases, ranging from cardiometabolic diseases, cancer, and cognitive disorders to respiratory pathologies and conditions that involve dysregulated metabolism. Because of the importance of systems-level interpretation, many methods have been developed to identify biologically significant pathways using metabolomics data. In this review, we first describe a complete metabolomics workflow (sample preparation, data acquisition, pre-processing, downstream analysis, etc.). We then comprehensively review 24 approaches capable of performing functional analysis, including those that combine metabolomics data with other types of data to investigate the disease-relevant changes at multiple omics layers. We discuss their availability, implementation, capability for pre-processing and quality control, supported omics types, embedded databases, pathway analysis methodologies, and integration techniques. We also provide a rating and evaluation of each software, focusing on their key technique, software accessibility, documentation, and user-friendliness. Following our guideline, life scientists can easily choose a suitable method depending on method rating, available data, input format, and method category. More importantly, we highlight outstanding challenges and potential solutions that need to be addressed by future research. To further assist users in executing the reviewed methods, we provide wrappers of the software packages at https://github.com/tinnlab/metabolite-pathway-review-docker.PMID:39397425 | DOI:10.1093/bib/bbae498

Plant Pathol J. 2024 Oct;40(5):559-567. doi: 10.5423/PPJ.NT.06.2024.0087. Epub 2024 Oct 1.ABSTRACTContinuous use of synthetic fungicides has led to explosive emergence of fungicide-resistant microbes. Therefore, there are urgent needs for environmentally friendly antimicrobial agents with novel modes of action. This study investigated endolichenic fungi (ELF) as a source of antimicrobial compounds against various plant pathogens. We utilized an One Strain MAny Compounds (OSMAC) approach to enhance the chemical diversity of fourteen ELF. This involved cultivation of ELF in four growth media and subsequently assessing antimicrobial activities of culture extracts. Nearly half of the culture extracts exhibited antimicrobial activity against a Gram-positive bacterium, but showed minimal activity against Gram-negative bacteria tested. Notably, culture extracts from two ELF, Chaetomium globosum and Nodulisporium sp., demonstrated significant inhibitory effects against plant pathogenic fungi. LC-MS/MS-based metabolome profiling confirmed the presence of known bioactive compounds like cyclic dipeptides and chaetoglobosins. These findings highlight the effectiveness of combining OSMAC and metabolomics for identifying antimicrobial agents for agricultural use.PMID:39397309 | DOI:10.5423/PPJ.NT.06.2024.0087

Metabolomics. 2024 Oct 13;20(6):117. doi: 10.1007/s11306-024-02173-4.ABSTRACTINTRODUCTION: Large variations in fatty and amino acid natural 2H/1H ratios in reference with solvent water point to the active involvement of compartmental, inter- and intramolecular deuterium disequilibrium in adaptive biology. Yet, the human deutenome is an untapped area of energy metabolism and health in humans.OBJECTIVES: The purpose of this scoping review is to examine health effects through deuterium homeostasis using deuterium-depleted water and/or a deuterium-depleted diet. We also aim to reveal health effects of nutritional, metabolic and exercise ketosis, i.e. complete mitochondrial fatty acid oxidation with the production of deuterium depleted (deupleted) metabolic water.METHODS: A protocol process approach was used to retrieve current research in deuterium depletion according to the preferred reporting items protocol for systematic reviews and meta-analyses, extension for scoping reviews with checklist (PRISMA-ScR).RESULTS: Fifteen research articles were used. All retrieved articles were heterogenous in nature and additional themes did not evolve. Deuterium depletion was found to have beneficial health effects in the following conditions: cancer prevention, cancer treatment, depression, diabetes, long-term memory, anti-aging, and sports performance. Deutenomics is actively pursued in drug research and there are biomarker roles attributed to large natural variations with adaptive significance in biology.CONCLUSION: Even with limited data, consistent deuterium depletion can be seen across all conditions reviewed. More randomized control trials are recommended to confirm cause and effect for translationally and clinically informed integrative nutrition-based medical interventions.PMID:39397213 | PMC:PMC11471703 | DOI:10.1007/s11306-024-02173-4

World J Microbiol Biotechnol. 2024 Oct 14;40(11):346. doi: 10.1007/s11274-024-04087-8.ABSTRACTPhosphate-solubilizing bacteria (PSB) can solubilize soil fixed phosphorus (P) to plant available forms. In previous studies, the mechanisms of inorganic phosphate solubilization by PSB mostly focused on the acidolysis of organic acids. Here we screened a highly efficient PSB, Advenella kashmirensis DF12, with the maximum P solubilization of 590 mg L- 1 at 6 days. In addition to its P solubilizing ability, DF12 also showed a tolerance to pH from 5 to 10 and a nitrogen fixation potential. The multiple functions of DF12 and its wide adaptability to various environmental conditions make it a promising biofertilizer candidate. The combined analysis of extracellular metabolites and intracellular metabolome data revealed that the production of organic acid (mainly gluconic acid) is not the only mechanism of P solubilized by DF12, the solubilized P content was not correlated with the gluconic acid concentration but was in a highly significant positive correlation with proton concentration, extrusion of proton during NH4+ assimilation plays a key role in phosphate solubilization. Moreover, the contribution of NH4+ assimilation to phosphorus solubilization is generally present in PSB. Therefore, we proposed that applying ammonium fertilizer in P-deficient soil is more appropriate, it can not only supplement nitrogen fertilizer, but also enhance P use efficiency, which contributes to worldwide fertilizer use reduction and efficiency improvement.PMID:39397206 | DOI:10.1007/s11274-024-04087-8

Metabolomics. 2024 Oct 13;20(6):114. doi: 10.1007/s11306-024-02176-1.ABSTRACTINTRODUCTION: Over the past two decades, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics has experienced significant growth, playing a crucial role in various scientific disciplines. However, despite these advance-ments, metabolite identification (MetID) remains a significant challenge. To address this, stringent MetID requirements were established, emphasizing the necessity of aligning experimental data with authentic reference standards using multiple criteria. Establishing dependable methods and corresponding libraries is crucial for instilling confidence in MetID and driving further progress in metabolomics.OBJECTIVE: The EMBL-MCF 2.0 LC-MS/MS method and public library was designed to facilitate both targeted and untargeted metabolomics with exclusive focus on endogenous, polar metabolites, which are known to be challenging to analyze due to their hydrophilic nature. By accompanying spectral data with robust retention times obtained from authentic standards and low-adsorption chromatography, high confidence MetID is achieved and accessible to the metabolomics community.METHODS: The library is built on hydrophilic interaction liquid chromatography (HILIC) and state-of-the-art low adsorption LC hardware. Both high-resolution tandem mass spectra and manually optimized multiple reaction monitoring (MRM) transitions were acquired on an Orbitrap Exploris 240 and a QTRAP 6500+, respectively.RESULTS: Implementation of biocompatible HILIC has facilitated the separation of isomeric metabolites with significant enhancements in both selectivity and sensitivity. The resulting library comprises a diverse collection of more than 250 biologically relevant metabolites. The methodology was successfully applied to investigate a variety of biological matrices, with exemplary findings showcased using murine plasma samples.CONCLUSIONS: Our work has resulted in the development of the EMBL-MCF 2.0 library, a powerful resource for sensitive metabolomics analyses and high-confidence MetID. The library is freely accessible and available in the universal .msp file format under the CC-BY 4.0 license: mona.fiehnlab.ucdavis.edu https://mona.fiehnlab.ucdavis.edu/spectra/browse?query=exists(tags.text:%27EMBL-MCF_2.0_HRMS_Library%27) , EMBL-MCF 2.0 HRMS https://www.embl.org/groups/metabolomics/instrumentation-and-software/#MCF-library .PMID:39397202 | PMC:PMC11471713 | DOI:10.1007/s11306-024-02176-1

Metabolomics. 2024 Oct 13;20(6):116. doi: 10.1007/s11306-024-02181-4.ABSTRACTBACKGROUND: Dopaminergic neurons from the substantia nigra pars compacta (SNc) have a higher susceptibility to aging-related degeneration, compared to midbrain dopaminergic cells present in the ventral tegmental area (VTA); the death of dopamine neurons in the SNc results in Parkinson´s disease (PD). In addition to increased loss by aging, dopaminergic neurons from the SNc are more prone to cell death when exposed to genetic or environmental factors, that either interfere with mitochondrial function, or cause an increase of oxidative stress. The oxidation of dopamine is a contributing source of reactive oxygen species (ROS), but this production is not enough to explain the differences in susceptibility to degeneration between SNc and VTA neurons.AIM OF REVIEW: In this review we aim to highlight the intrinsic differences between SNc and VTA dopamine neurons, in terms of gene expression, calcium oscillations, bioenergetics, and ROS responses. Also, to describe the changes in the pentose phosphate pathway and the induction of apoptosis in SNc neurons during aging, as related to the development of PD.KEY SCIENTIFIC CONCEPTS OF REVIEW: Recent work showed that neurons from the SNc possess intrinsic characteristics that result in metabolic differences, related to their intricate morphology, that render them more susceptible to degeneration. In particular, these neurons have an elevated basal energy metabolism, that is required to fulfill the demands of the constant firing of action potentials, but at the same time, is associated to higher ROS production, compared to VTA cells. Finally, we discuss how mutations related to PD affect metabolic pathways, and the related mechanisms, as revealed by metabolomics.PMID:39397188 | PMC:PMC11471710 | DOI:10.1007/s11306-024-02181-4

Metabolomics. 2024 Oct 13;20(6):115. doi: 10.1007/s11306-024-02183-2.NO ABSTRACTPMID:39397170 | PMC:PMC11471698 | DOI:10.1007/s11306-024-02183-2

Sci Rep. 2024 Oct 14;14(1):23959. doi: 10.1038/s41598-024-74738-1.ABSTRACTThe current study explores the effects of microwave treatment at varying wattage and durations on the phytoconstituents, antioxidant status, anti-nutritional factors (ANFs), and metabolite profiles of de-oiled rice bran. The total phenolics and flavonoids showed both increases and decreases depending on specific microwave parameters, while flavonol content consistently increased across all treated groups compared to the control. The DPPH and ABTS free radical scavenging activity, total antioxidant capacity, FRAP, CUPRAC, metal chelating activity, and ascorbic acid content were enhanced in most of the microwaved samples; however, longer microwave exposure at higher wattage led to their reduction. A treatment-specific decrease in ANFs, including condensed tannins, oxalates, and phytates, was observed. HRMS-based untargeted metabolomics identified a diverse range of primary and secondary metabolites, which clustered in a group-specific manner, indicating notable group-wise metabolite variations. Analysis of discriminating metabolites revealed no significant differences in the overall levels of phenolics, flavonoids, vitamins and cofactors, sugars, amino acids, terpenoids, fatty acids, and their derivatives among the treated groups compared to the control; however, several individual metabolites within these metabolite classes differed significantly. These findings suggest that optimized microwaving of de-oiled rice bran can enhance phytochemicals and antioxidants while improving the metabolite profile.PMID:39397141 | PMC:PMC11471765 | DOI:10.1038/s41598-024-74738-1

Sci Rep. 2024 Oct 13;14(1):23930. doi: 10.1038/s41598-024-75225-3.ABSTRACTExposure to ionizing radiation induces cellular and molecular damage leading to a cascade of events resulting in tissue and organ injury. Our study strives to characterize and validate metabolomic changes in preterminal stage (immediately prior to death) samples collected from rhesus macaques lethally irradiated with one of two different doses of radiation. Peripheral blood samples were collected pre-exposure, post-exposure, and at the preterminal stage of nonhuman primates (NHPs that did not survive exposure with 7.2 Gy or 7.6 Gy total-body radiation (LD60-80/60)). We analyzed global metabolomic alterations using ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight mass spectrometry (QTOF-MS) in serum samples collected at various timepoints in relation to radiation exposure. The goal of this study was to validate the metabolic shifts present in samples collected just prior to death, which were reported earlier in a preliminary study with a limited number of samples and a single dose of radiation. Here, we demonstrate that radiation exposure induced significant time-dependent metabolic alterations compared with pre-exposure samples. We observed significant metabolite dysregulation in animals exposed to 7.6 Gy compared to 7.2 Gy. Greater metabolic disruption was observed in the preterminal groups than all of the other post-irradiation timepoints in both cohorts. Metabolomic shifts in these preterminal groups also revealed consistent disturbances in sphingolipid metabolism, steroid hormone biosynthesis, and glycerophospholipid metabolism pathways. Overall, the sphingolipid metabolism pathway appears to be representative of the preterminal phenotype, confirming the results of our preliminary study. These results offer important and novel insights for identification and validation of biomarkers for lethality, and such observations would be valuable for triage during a radiological/nuclear mass casualty scenario.PMID:39397118 | PMC:PMC11471850 | DOI:10.1038/s41598-024-75225-3

Food Chem X. 2024 Aug 8;23:101721. doi: 10.1016/j.fochx.2024.101721. eCollection 2024 Oct 30.ABSTRACTRoasting is a key process in the production of large-leaf yellow tea (LYT). In this study, we synthesized metabolomics and electronic-tongue analysis to compare the quality of charcoal-roasted, electric-roasted and drum-roasted LYT. Charcoal-roasted LYT had the highest yellowness and redness, drum-roasted LYT had a more prominent umami and brightness, and electric roasting reduced astringency. A total of 48 metabolites were identified by metabolomics. Among these, leucocyanidin, kaempferol, luteolin-7-lactate, and apigenin-7-O-neohesperidoside might affect the brightness and yellowness. Theanine, aspartic acid, and glutamic acid contents significantly and positively correlated with umami levels, and the high retention of flavonoid glycosides and catechins in drum-roasted LYT contributed to its astringency. These findings elucidate the contribution of the roasting method to the quality of LYT and provide a theoretical basis for LYT production.PMID:39229616 | PMC:PMC11369393 | DOI:10.1016/j.fochx.2024.101721