PubMed

New Phytol. 2023 Dec 20. doi: 10.1111/nph.19490. Online ahead of print.ABSTRACTBy modifying the biotic and abiotic properties of the soil, plants create soil legacies that can affect vegetation dynamics through plant-soil feedbacks (PSF). PSF are generally attributed to reciprocal effects of plants and soil biota, but these interactions can also drive changes in the identity, diversity and abundance of soil metabolites, leading to more or less persistent soil chemical legacies whose role in mediating PSF has rarely been considered. These chemical legacies may interact with microbial or nutrient legacies to affect species coexistence. Given the ecological importance of chemical interactions between plants and other organisms, a better understanding of soil chemical legacies is needed in community ecology. In this Viewpoint, we aim to: highlight the importance of belowground chemical interactions for PSF; define and integrate soil chemical legacies into PSF research by clarifying how the soil metabolome can contribute to PSF; discuss how functional traits can help predict these plant-soil interactions; propose an experimental approach to quantify plant responses to the soil solution metabolome; and describe a testable framework relying on root economics and seed dispersal traits to predict how plant species affect the soil metabolome and how they could respond to soil chemical legacies.PMID:38124274 | DOI:10.1111/nph.19490

Rapid Commun Mass Spectrom. 2024 Jan 30;38(2):e9670. doi: 10.1002/rcm.9670.ABSTRACTRATIONALE: Multicellular tumor spheroids (MCTSs) that reconstitute the metabolic characteristics of in vivo tumor tissue may facilitate the discovery of molecular biomarkers and effective anticancer therapies. However, little is known about how cancer cells adapt their metabolic changes in complex three-dimensional (3D) microenvironments. Here, using the two-dimensional (2D) cell model as control, the metabolic phenotypes of glioma U87MG multicellular tumor spheroids were systematically investigated based on static metabolomics and dynamic fluxomics analysis.METHODS: A liquid chromatography-mass spectrometry-based global metabolomics and lipidomics approach was adopted to survey the cellular samples from 2D and 3D culture systems, revealing marked molecular differences between them. Then, by means of metabolomic pathway analysis, the metabolic pathways altered in glioma MCTSs were found using 13 C6 -glucose as a tracer to map the metabolic flux of glycolysis, the tricarboxylic acid (TCA) cycle, de novo nucleotide synthesis, and de novo lipid biosynthesis in the MCTS model.RESULTS: We found nine metabolic pathways as well as glycerolipid, glycerophospholipid and sphingolipid metabolism to be predominantly altered in glioma MCTSs. The reduced nucleotide metabolism, amino acid metabolism and glutathione metabolism indicated an overall lower cellular activity in MCTSs. Through dynamic fluxomics analysis in the MCTS model, we found that cells cultured in MCTSs exhibited increased glycolysis activity and de novo lipid biosynthesis activity, and decreased the TCA cycle and de novo purine nucleotide biosynthesis activity.CONCLUSIONS: Our study highlights specific, altered biochemical pathways in MCTSs, emphasizing dysregulation of energy metabolism and lipid metabolism, and offering novel insight into metabolic events in glioma MCTSs.PMID:38124173 | DOI:10.1002/rcm.9670

BMC Bioinformatics. 2023 Dec 20;24(1):489. doi: 10.1186/s12859-023-05598-1.ABSTRACTBACKGROUND: Plate design is a necessary and time-consuming operation for GC/LC-MS-based sample preparation. The implementation of the inter-batch balancing algorithm and the intra-batch randomization algorithm can have a significant impact on the final results. For researchers without programming skills, a stable and efficient online service for plate design is necessary.RESULTS: Here we describe InjectionDesign, a free online plate design service focused on GC/LC-MS-based multi-omics experiment design. It offers the ability to separate the position design from the sequence design, making the output more compatible with the requirements of a modern mass spectrometer-based laboratory. In addition, it has implemented an optimized block randomization algorithm, which can be better applied to sample stratification with block randomization for an unbalanced distribution. It is easy to use, with built-in support for common instrument models and quick export to a worksheet.CONCLUSIONS: InjectionDesign is an open-source project based on Java. Researchers can get the source code for the project from Github: https://github.com/CSi-Studio/InjectionDesign . A free web service is also provided: http://www.injection.design .PMID:38124029 | DOI:10.1186/s12859-023-05598-1

Cerebellum. 2023 Dec 20. doi: 10.1007/s12311-023-01641-2. Online ahead of print.ABSTRACTCells configure their metabolism in a synchronized and timely manner to meet their energy demands throughout development and adulthood. Transitions of developmental stages are coupled to metabolic shifts, such that glycolysis is highly active during cell proliferation, whereas oxidative phosphorylation prevails in postmitotic states. In the cerebellum, metabolic transitions are remarkable given its protracted developmental timelines. Such distinctive feature, along with its high neuronal density and metabolic demands, make the cerebellum highly vulnerable to metabolic insults. Despite the expansion of metabolomic approaches to uncover biological mechanisms, little is known about the role of metabolism on cerebellar development and maintenance. To illuminate the intricate connections between metabolism, physiology, and cerebellar disorders, we examined here the impact of metabolism on cerebellar growth, maturation, and adulthood through the lens of inborn errors of metabolism.PMID:38123901 | DOI:10.1007/s12311-023-01641-2

Sci Rep. 2023 Dec 19;13(1):22704. doi: 10.1038/s41598-023-50069-5.ABSTRACTThe consumption of fructose has increased dramaticly during the last few decades, inducing a great increase in the risk of intrahepatic lipid accumulation, hypertriglyceridemia, hyperuricemia and cancer. However, the underlying mechanism has not yet been fully elucidated. Amino acid metabolism may play an important role in the process of the diseases caused by fructose, but there is still a lack of corresponding evidence. In present study, we provide an evidence of how fructose affects amino acids metabolism in 1895 ordinary residents in Chinese community using UPLC-QqQMS based amino acid targeted metabolomics and the underlying mechanism of fructose exposure how interferes with amino acid metabolism related genes and acetylated modification of proteome in the liver of rats model. We found people with high fructose exposure had higher levels of Asa, EtN, Asp, and Glu, and lower levels of 1MHis, PEtN, Arg, Gln, GABA, Aad, Hyl and Cys. The further mechanism study displayed amino acid metabolic genes of Aspa, Cndp1, Dbt, Dmgdh, and toxic metabolites such as N-acetylethanolamines accumulation, interference of urea cycle, as well as acetylated modification of key enzymes in glutamine metabolic network and glutamine derived NEAAs synthesis pathway in liver may play important roles in fructose caused reprogramming in amino acid metabolism. This research provides novel insights of the mechanism of amino acid metabolic disorder caused by fructose and supplies new targets for clinical therapy.PMID:38123624 | DOI:10.1038/s41598-023-50069-5

Nat Commun. 2023 Dec 20;14(1):8488. doi: 10.1038/s41467-023-44035-y.ABSTRACTDespite the increasing availability of tandem mass spectrometry (MS/MS) community spectral libraries for untargeted metabolomics over the past decade, the majority of acquired MS/MS spectra remain uninterpreted. To further aid in interpreting unannotated spectra, we created a nearest neighbor suspect spectral library, consisting of 87,916 annotated MS/MS spectra derived from hundreds of millions of MS/MS spectra originating from published untargeted metabolomics experiments. Entries in this library, or "suspects," were derived from unannotated spectra that could be linked in a molecular network to an annotated spectrum. Annotations were propagated to unknowns based on structural relationships to reference molecules using MS/MS-based spectrum alignment. We demonstrate the broad relevance of the nearest neighbor suspect spectral library through representative examples of propagation-based annotation of acylcarnitines, bacterial and plant natural products, and drug metabolism. Our results also highlight how the library can help to better understand an Alzheimer's brain phenotype. The nearest neighbor suspect spectral library is openly available for download or for data analysis through the GNPS platform to help investigators hypothesize candidate structures for unknown MS/MS spectra in untargeted metabolomics data.PMID:38123557 | DOI:10.1038/s41467-023-44035-y

Nat Commun. 2023 Dec 20;14(1):8469. doi: 10.1038/s41467-023-44266-z.ABSTRACTEffective early-stage markers for predicting which patients are at risk of developing SARS-CoV-2 infection have not been fully investigated. Here, we performed comprehensive serum metabolome analysis of a total of 83 patients from two cohorts to determine that the acceleration of amino acid catabolism within 5 days from disease onset correlated with future disease severity. Increased levels of de-aminated amino acid catabolites involved in the de novo nucleotide synthesis pathway were identified as early prognostic markers that correlated with the initial viral load. We further employed mice models of SARS-CoV2-MA10 and influenza infection to demonstrate that such de-amination of amino acids and de novo synthesis of nucleotides were associated with the abnormal proliferation of airway and vascular tissue cells in the lungs during the early stages of infection. Consequently, it can be concluded that lung parenchymal tissue remodeling in the early stages of respiratory viral infections induces systemic metabolic remodeling and that the associated key amino acid catabolites are valid predictors for excessive inflammatory response in later disease stages.PMID:38123556 | DOI:10.1038/s41467-023-44266-z

Tree Physiol. 2023 Dec 20:tpad154. doi: 10.1093/treephys/tpad154. Online ahead of print.ABSTRACTAnthocyanins are flavonoid-like substances that play important roles in plants in adaptation to various environmental stresses. In this research, we discovered that cytokinin (CK) alone could effectively induce the anthocyanin biosynthesis in Eucalyptus and many other perennial woody plant species, but not in tobacco and Arabidopsis, suggesting a diverse role of CK in regulating anthocyanin biosynthesis in different species. Transcriptomic and metabolomic strategies were used to further clarify the specific role of CK in regulating anthocyanin biosynthesis in Eucalyptus. The results showed that 801 and 2241 genes were differentially regulated at 6 and 24 h, respectively, after CK treatment. Pathway analysis showed that most of the differentially expressed genes were categorized into pathways related to cellular metabolism or transport of metabolites, including amino acids and sugars. The metabolomic results well supported the transcriptome data, which showed that most of the differentially regulated metabolites were related to the metabolism of sugar, amino acids, and flavonoids. Moreover, CK treatment significantly induced the accumulation of sucrose in the CK-treated leaves, while sugar starvation mimicked by either defoliation or shading treatment of the basal leaves significantly reduced the sugar increase of the CK-treated leaves, and thus inhibited CK-induced anthocyanin biosynthesis. The results of in vitro experiment also suggested that CK-induced anthocyanin in Eucalyptus was sugar-dependent. Furthermore, we identified an early CK-responsive transcription factor MYB113 in Eucalyptus, the expression of which was significantly upregulated by CK treatment in Eucalyptus but inhibited in Arabidopsis. Importantly, overexpression of EgrMYB113 in the Eucalyptus hairy roots was associated with significant anthocyanin accumulation, and upregulation of most of the anthocyanin biosynthetic genes. In conclusion, our study demonstrates a key role of CK in the regulation of anthocyanin biosynthesis in Eucalyptus, providing a molecular basis for further understanding the regulatory mechanism, and diversity of hormone-regulated anthocyanin biosynthesis in different plant species.PMID:38123502 | DOI:10.1093/treephys/tpad154

Zhonghua Xin Xue Guan Bing Za Zhi. 2023 Dec 24;51(12):1247-1255. doi: 10.3760/cma.j.cn112148-20231008-00254.ABSTRACTObjective: By identifying different metabolites in the serum and clarifying the potential metabolic disorder pathways in metabolic syndrome (MS) and stable coronary artery disease patients, to evaluate the predictive value of specific metabolites based on serum metabolomics for the occurrence of MS and coronary heart disease in overweight or obese populations. Methods: This is a retrospective cross-sectional study. Patients with Metabolic Syndrome (MS group), patients with stable coronary heart disease (coronary heart disease group), and overweight or obese individuals (control group) recruited from the Central District of the First Affiliated Hospital of Zhengzhou University from 2017 to 2019 were assigned to the training set, meanwhile, the corresponding three groups of people recruited from the East District of the hospital during the same period were assigned to the validation test. The serum metabolomics profiles were determined by ultra-performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). Clinical characteristics (age, gender, body mass index (BMI), blood pressure, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), alanine aminotransferase (ALT), aspartate transaminase (AST), total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glomerular filtration rate (eGFR), creatinine (CR)) were also collected. Based on the orthogonal partial least-squares discrimination analysis (OPLS-DA) model, the significantly changed metabolites for MS and coronary artery disease patients were screened according to variable important in projection (VIP), and the receiver operating characteristic (ROC) analysis was evaluated for the risk prediction values of changed metabolites. Results: A total of 488 subjects were recruited in this study, the training set included 40 MS, 249 coronary artery disease patients and 148 controls, the validation set included 16 MS, 18 coronary artery disease patients and 17 controls. We made comparisons of the serum metabolites of coronary artery disease vs. controls, MS vs. controls, and coronary artery disease vs. MS, and a total of 22 different metabolites were identified. The disturbed metabolic pathways involved were phospholipid metabolism, amino acid metabolism, purine metabolism and other pathways. Through cross-comparisons, we identified 2 specific metabolites for MS (phosphatidylcholine (18∶1(9Z)e/20) and pipecolic acid), 4 specific metabolites for coronary artery disease (lysophosphatidylcholine (17∶0), PC(16∶0/16∶0), hypoxanthine and histidine), and 4 common metabolites both for MS and coronary artery disease (isoleucine, phenylalanine, glutathione and LysoPC(14∶0)). Based on the cut-off values from ROC curve, the predictive value of the above metabolites for the occurrence of MS in overweight or obese populations is 100%, the predictive value for the occurrence of coronary heart disease is 87.5%, and the risk predictive value for coronary heart disease in MS patients is 82.1%. Conclusions: The altered serum metabolites suggest that MS and coronary heart disease may involve multiple metabolic pathway disorders. Specific metabolites based on serum metabolomics have good predictive value for the occurrence of MS and coronary heart disease in overweight or obese populations.PMID:38123207 | DOI:10.3760/cma.j.cn112148-20231008-00254

J Cachexia Sarcopenia Muscle. 2023 Dec 20. doi: 10.1002/jcsm.13406. Online ahead of print.ABSTRACTBACKGROUND: Lipid hydroperoxides (LOOH) have been implicated in skeletal muscle atrophy with age and disuse. Lysophosphatidylcholine acyltransferase 3 (LPCAT3), an enzyme of the Lands cycle, conjugates a polyunsaturated fatty acyl chain to a lysophospholipid to form a polyunsaturated fatty acid containing phospholipid (PUFA-PL) molecule, providing substrates for LOOH propagation. Previous studies suggest that inhibition of the Lands cycle is an effective strategy to suppress LOOH. Mice with skeletal muscle-specific tamoxifen-inducible knockout of LPCAT3 (LPCAT3-MKO) were utilized to determine if muscle-specific attenuation of LOOH may alleviate muscle atrophy and weakness with disuse.METHODS: LPCAT3-MKO and control mice underwent 7 days of sham or hindlimb unloading (HU model) to study muscle mass and force-generating capacity. LOOH was assessed by quantifying 4-hydroxynonenal (4-HNE)-conjugated peptides. Quantitative PCR and lipid mass spectrometry were used to validate LPCAT3 deletion.RESULTS: Seven days of HU was sufficient to induce muscle atrophy and weakness concomitant to a ~2-fold increase in 4-HNE (P = 0.0069). Deletion of LPCAT3 reversed HU-induced increase in muscle 4-HNE (P = 0.0256). No difference was found in body mass, body composition, or caloric intake between genotypes. The soleus (SOL) and plantaris (PLANT) muscles of the LPCAT3-MKO mice experienced ~15% and ~40% less atrophy than controls, respectively. (P = 0.0011 and P = 0.0265). Type I and IIa SOL myofibers experienced a ~40% decrease in cross sectional area (CSA), which was attenuated to only 15% in the LPCAT3-MKO mice (P = 0.0170 and P = 0.0411, respectively). Strikingly, SOL muscles were fully protected and extensor digitorum longus (EDL) muscles experienced a ~35% protection from HU-induced reduction in force-generating capacity in the LPCAT3-MKO mice compared with controls (P < 0.0001 for both muscles).CONCLUSIONS: Our findings demonstrate that attenuation of skeletal muscle lipid hydroperoxides is sufficient to restore its function, in particular a protection from reduction in muscle specific force. Our findings suggest muscle lipid peroxidation contributes to atrophy and weakness induced by disuse in mice.PMID:38123161 | DOI:10.1002/jcsm.13406

Sci Total Environ. 2023 Dec 18:169351. doi: 10.1016/j.scitotenv.2023.169351. Online ahead of print.ABSTRACTTo investigate microbial communities and their contributions to carbon and nutrient cycling along water gradients can enhance our comprehension of climate change impacts on ecosystem services. Thus, we conducted an assessment of microbial communities, metagenomic functions, and metabolomic profiles within four ecosystems, i.e., desert grassland (DG), shrub-steppe (SS), forest (FO), and marsh (MA) in the Altai region of Xinjiang, China. Our results showed that soil total carbon (TC), total nitrogen, NH4+, and NO3- increased, but pH decreased with soil water gradients. Microbial abundances and richness also increased with soil moisture except the abundances of fungi and protists being lowest in MA. A shift in microbial community composition is evident along the soil moisture gradient, with Proteobacteria, Basidiomycota, and Evosea proliferating but a decline in Actinobacteria and Cercozoa. The β-diversity of microbiomes, metagenomic, and metabolomic functioning were correlated with soil moisture gradients and have significant associations with specific soil factors of TC, NH4+, and pH. Metagenomic functions associated with carbohydrate and DNA metabolisms, as well as phages, prophages, TE, plasmids functions diminished with moisture, whereas the genes involved in nitrogen and potassium metabolism, along with certain biological interactions and environmental information processing functions, demonstrated an augmentation. Additionally, MA harbored the most abundant metabolomics dominated by lipids and lipid-like molecules and organic oxygen compounds, except certain metabolites showing decline trends along water gradients, such as N'-Hydroxymethylnorcotinine and 5-Hydroxyenterolactone. Thus, our study suggests that future ecosystem succession facilitated by changes in rainfall patterns will significantly alter soil microbial taxa, functional potential, and metabolite fractions.PMID:38123079 | DOI:10.1016/j.scitotenv.2023.169351

Life Sci. 2023 Dec 18:122357. doi: 10.1016/j.lfs.2023.122357. Online ahead of print.ABSTRACTThe gut-brain axis is gaining more attention in neurodevelopmental disorders, especially autism spectrum disorder (ASD). Many factors can influence microbiota in early life, including host genetics and perinatal events (infections, mode of birth/delivery, medications, nutritional supply, and environmental stressors). The gut microbiome can influence blood-brain barrier (BBB) permeability, drug bioavailability, and social behaviors. Developing microbiota-based interventions such as probiotics, gastrointestinal (GI) microbiota transplantation, or metabolite supplementation may offer an exciting approach to treating ASD. This review highlights that RNA sequencing, metabolomics, and transcriptomics data are needed to understand how microbial modulators can influence ASD pathophysiology. Due to the substantial clinical heterogeneity of ASD, medical caretakers may be unlikely to develop a broad and effective general gut microbiota modulator. However, dietary modulation followed by administration of microbiota modulators is a promising option for treating ASD-related behavioral and gastrointestinal symptoms. Future work should focus on the accuracy of biomarker tests and developing specific psychobiotic agents tailored towards the gut microbiota seen in ASD patients, which may include developing individualized treatment options.PMID:38123016 | DOI:10.1016/j.lfs.2023.122357

Toxicology. 2023 Dec 18:153709. doi: 10.1016/j.tox.2023.153709. Online ahead of print.ABSTRACTExposure to air pollutants has been associated with various adverse health outcomes, including chronic obstructive pulmonary disease (COPD). However, the precise underlying mechanism by which air pollution impacts COPD through remains insufficiently understood. To elucidated the molecular mechanism by which air pollutant exposure contributes to alterations in the gut microbiome and metabolism in AECOPD patients, we employed metagenomics and untargeted metabolomics to analyse the gut microbial, faecal, and serum metabolites. The correlations among air pollutants, gut microbes, serum metabolites, and blood biochemical markers were assessed using generalized additive mixed models and Spearman correlation analysis. The findings revealed that for every 10μg/m3 increase in PM2.5 concentration, the α-diversity of the gut flora decreased by 2.16% (95% CI: 1.80%-2.53%).We found seven microorganisms that were significantly associated with air pollutants, of which Enterococcus faecium, Bacteroides fragilis, Ruthenibacterium lactatiformans, and Subdoligranulum sp.4_3_54A2FAA were primarily associated with glycolysis. We identified 13 serum metabolites and 17 faecal metabolites significantly linked to air pollutants. Seven of these metabolites, which were strongly associated with air pollutants and blood biochemical indices, were found in both serum and faecal samples. Some of these metabolites, such as 2,5-furandicarboxylic acid, C-8C1P and melatonin, were closely associated with disturbances in lipid and fatty acid metabolism in AECOPD patients. These findings underscore the impact of air pollutants on overall metabolism based on influencing gut microbes and metabolites in AECOPD patients. Moreover, these altered biomarkers establish the biologic connection between air pollutant exposure and AECOPD outcomes.The identification of pertinent biomarkers provides valuable insights for the development of precision COPD prevention strategies.PMID:38123012 | DOI:10.1016/j.tox.2023.153709

Bioresour Technol. 2023 Dec 18:130216. doi: 10.1016/j.biortech.2023.130216. Online ahead of print.ABSTRACTBrewer's spent grain (BSG) is a main byproduct of the beer industry. BSG is rich in a variety of nutrients, and the search for its effective, high-value utilization is ongoing. Environmental probiotic factor γ-PGA was produced by fermenting Bacillus subtilis with BSG substrate and the fermenting grain components were analyzed. The γ-PGA yield reached 31.58 ± 0.21 g/kg of BSG. Gas chromatography-mass spectrometry and non-targeted metabolomics analyses revealed 73 new volatile substances in the fermenting grains. Furthermore, 2,376 metabolites were upregulated after fermentation and several components were beneficial for plant growth and development (such as ectoine, acetyl eugenol, L-phenylalanine, niacin, isoprene, pantothenic acid, dopamine, glycine, proline, jasmonic acid, etc). These results show that it is possible to synthesize adequate amounts of γ-PGA for use as a functional fertilizer.PMID:38122994 | DOI:10.1016/j.biortech.2023.130216

Free Radic Biol Med. 2023 Dec 18:S0891-5849(23)01148-6. doi: 10.1016/j.freeradbiomed.2023.12.003. Online ahead of print.ABSTRACTReactive oxygen and nitrogen species (RONS) are a range of chemical individuals produced by living cells that contribute to the proper functioning of organisms. Cells under oxidative and nitrative stress show excessive production of RONS (including hydrogen peroxide, H2O2, hypochlorous acid, HOCl, and peroxynitrite, ONOO-) which may result in a damage proteins, lipids, and genetic material. Thus, the development of probes for in vivo detection of such oxidants is an active area of research, focusing on molecular redox sensors, including boronate-caged fluorophores. Here, we report a boronate-based styryl probe with a cationic pyridinium moiety (BANEP+) for the fluorescent detection of selected biological oxidants in vitro and in vivo. We compare the chemical reactivity of the BANEP+ probe toward H2O2, HOCl, and ONOO- and examine the influence of the major intracellular non-enzymatic antioxidant molecule, glutathione (GSH). We demonstrate that, at the physiologically relevant GSH concentration, the BANEP+ probe is efficiently oxidized by peroxynitrite, forming its phenolic derivative HNEP+. GSH does not affect the fluorescence properties of the BANEP+ and HNEP+ dyes. Finally, we report the identification of a novel type of molecular marker, with the boronate moiety replaced by the iodine atom, formed from the probe in the presence of HOCl and iodide anion. We conclude that the reported chemical reactivity and structural features of the BANEP+ probe may be a basis for the development of new red fluorescent probes for in vitro and in vivo detection of ONOO-.PMID:38122872 | DOI:10.1016/j.freeradbiomed.2023.12.003

Ocul Surf. 2023 Dec 18:S1542-0124(23)00156-8. doi: 10.1016/j.jtos.2023.12.005. Online ahead of print.ABSTRACTPURPOSE: Herpes simplex keratitis (HSK), caused by type 1 herpes simplex virus (HSV) reactivation, is a severe infectious disease that leads to vision loss. HSV can trigger metabolic reprogramming in the host cell and change the extracellular vesicles (EV) cargos; however, little is known about the EV metabolic signatures during ocular HSV infection. Here, we aimed to depict the EV-associated metabolic landscape in HSK patients' tears.METHODS: We collected 82 samples from 41 participants with unilateral HSK (contralateral unaffected tears were set as negative control), including subtype cohorts of 13 epithelial, 20 stromal, and 8 endothelial HSK. We isolated tear EVs via our previously established platform and conducted metabolic analysis using LC-MS/MS. The metabolic signatures for recognizing HSK and subtypes were assessed through differential analysis and machine learning algorithms.RESULTS: Hypopsia and increased extracellular CD63 levels were observed in affected eyes. We identified 339 metabolites based on sEVs isolated from tears. Differential analysis revealed alterations in energy and amino acid metabolism, as well as the infectious microenvironment. Furthermore, we observed dysregulated metabolite such as methyldopa, which is associated with inappropriate neovascularization and corneal sensation loss, contributing to the HSK severity particularly in the stromal subtype. Moreover, machine learning classification also suggested a set of EV metabolic signatures that have potential for pan-keratitis detection.CONCLUSIONS: Our findings demonstrate that tear EV metabolites can serve as valuable indicators for comprehending the underlying pathological mechanisms. This knowledge is expected to facilitate the development of liquid biopsy means and therapeutic target discovery.PMID:38122863 | DOI:10.1016/j.jtos.2023.12.005

J Nutr. 2023 Dec 18:S0022-3166(23)72812-5. doi: 10.1016/j.tjnut.2023.12.023. Online ahead of print.ABSTRACTBACKGROUND: Identifying biological drivers of mammographic breast density (MBD), a strong risk factor for breast cancer, could provide insight into breast cancer etiology and prevention. Studies on dietary factors and MBD have yielded conflicting results. There is, however, very limited data on the associations of dietary biomarkers and MBD.OBJECTIVE: We aimed to investigate the associations of vitamins and related cofactor metabolites with MBD in premenopausal women.METHODS: We measured 37 vitamins and related cofactor metabolites in fasting plasma samples of 700 premenopausal women recruited during their annual screening mammogram at the Washington University School of Medicine, St. Louis, MO. Volpara was used to assess volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV). We estimated the least square means of VPD, DV, and NDV across quartiles of each metabolite, as well as the regression coefficient of a metabolite in continuous scale from multiple covariate-adjusted linear regression. We corrected for multiple testing using the Benjamini-Hochberg procedure to control the false discover rate (FDR) at a 5% level.RESULTS: Participants' mean VPD was 10.5%. Two vitamin A metabolites (beta-cryptoxanthin and carotene diol 2) were positively associated, and one vitamin E metabolite (gamma-tocopherol) was inversely associated with VPD. The mean VPD increased across quartiles of beta-cryptoxanthin (Q1=7.2%,Q2=7.7%,Q3=8.4%%,Q4=9.2%; p-for-trend=1.77E-05, FDR p-value=1.18E-03). There was a decrease in the mean VPD across quartiles of gamma-tocopherol (Q1=9.4%,Q2=8.1%,Q3=8.0%,Q4=7.8%; p-for-trend=4.01E-03, FDR p-value=0.04). Seven metabolites were associated with NDV: three vitamin E (gamma-CEHC glucuronide, delta-CEHC, and gamma-tocopherol) and one vitamin C (gulonate), were positively associated, while two vitamin A (carotene diol 2 and beta-cryptoxanthin) and one vitamin C (threonate) were inversely associated with NDV. No metabolite was significantly associated with DV.CONCLUSION: We report novel associations of vitamins and related cofactor metabolites with MBD in premenopausal women.PMID:38122846 | DOI:10.1016/j.tjnut.2023.12.023

Cell Rep Med. 2023 Dec 19;4(12):101341. doi: 10.1016/j.xcrm.2023.101341.ABSTRACTThe gut microbiota contributes to the pathophysiology of non-alcoholic fatty liver disease (NAFLD). Histidine is a key energy source for the microbiota, scavenging it from the host. Its role in NAFLD is poorly known. Plasma metabolomics, liver transcriptomics, and fecal metagenomics were performed in three human cohorts coupled with hepatocyte, rodent, and Drosophila models. Machine learning analyses identified plasma histidine as being strongly inversely associated with steatosis and linked to a hepatic transcriptomic signature involved in insulin signaling, inflammation, and trace amine-associated receptor 1. Circulating histidine was inversely associated with Proteobacteria and positively with bacteria lacking the histidine utilization (Hut) system. Histidine supplementation improved NAFLD in different animal models (diet-induced NAFLD in mouse and flies, ob/ob mouse, and ovariectomized rats) and reduced de novo lipogenesis. Fecal microbiota transplantation (FMT) from low-histidine donors and mono-colonization of germ-free flies with Enterobacter cloacae increased triglyceride accumulation and reduced histidine content. The interplay among microbiota, histidine catabolism, and NAFLD opens therapeutic opportunities.PMID:38118419 | DOI:10.1016/j.xcrm.2023.101341

Plant Physiol Biochem. 2023 Dec 14;206:108276. doi: 10.1016/j.plaphy.2023.108276. Online ahead of print.ABSTRACTSalinization of arable land has been progressively increasing, which, along with the effects of climate change, poses a serious risk to food production. Quinoa is a halophyte species that grows and is productive in highly saline soils. This study addresses the mechanisms of response and adaptation to high salinity. We show that the differential distribution of sodium in plants depends on the variety, observing that varieties such as Pandela Rosada limit the passage transit of sodium to the aerial part of the plant, a mechanism that seems to be regulated by sodium transporters such as HKT1s or SOS1. Like other halophytes of the Amaranthaceae family, quinoa plants have salt glands (bladder cells), which have been reported to play an important role in salt tolerance. However, our study shows that the contribution of bladder glands to salt accumulation is rather low. The 1H-NMR metabolome study of quinoa subjected to salt stress showed important modifications in the contents of amino acids, sugars, organic acids, and quaternary ammonium compounds (glycinebetaine). The compound with a higher presence was glycinebetaine, which makes up 6% of the leaf dry matter under saline conditions. Our findings suggest that glycinebetaine can act as an osmolyte and/or osmoprotectant, facilitating plant development under high saline ambient.PMID:38118328 | DOI:10.1016/j.plaphy.2023.108276

PLoS One. 2023 Dec 20;18(12):e0296047. doi: 10.1371/journal.pone.0296047. eCollection 2023.ABSTRACTBACKGROUND: Growing attention is paid to the association between alterations in the gut microbiota and their metabolites in patients with psychiatric disorders. Our study aimed to determine how gut microbiota and metabolomes are related to the sleep quality among patients with depression and anxiety disorders by analyzing the datasets of our previous study.METHODS: Samples were collected from 40 patients (depression: 32 patients [80.0%]); anxiety disorders: 8 patients [20.0%]) in this study. Gut microbiomes were analyzed using 16S rRNA gene sequencing and gut metabolomes were analyzed by a mass spectrometry approach. Based on the Pittsburgh Sleep Quality Index (PSQI), patients were categorized into two groups: the insomnia group (PSQI score ≥ 9, n = 20) and the non-insomnia group (PSQI score < 9, n = 20).RESULTS: The insomnia group showed a lower alpha diversity in the Chao1 and Shannon indices than the non-insomnia group after the false discovery rate (FDR) correction. The relative abundance of genus Bacteroides showed a positive correlation with PSQI scores in the non-insomnia group. The concentrations of glucosamine and N-methylglutamate were significantly higher in the insomnia group than in the non-insomnia group.CONCLUSIONS: Our findings suggest that specific taxa could affect the sleep quality among patients with depression and anxiety disorders. Further studies are needed to elucidate the impact of sleep on specific gut microbiota and metabolomes in depression and anxiety disorders.PMID:38117827 | DOI:10.1371/journal.pone.0296047