PubMed

Anal Chem. 2024 Nov 19. doi: 10.1021/acs.analchem.4c03966. Online ahead of print.ABSTRACTRobust annotation of compounds is a critical element in metabolomics. The 13C-detection NMR experiment incredible natural abundance double-quantum transfer experiment (INADEQUATE) stands out as a powerful tool for structural elucidation, but this valuable experiment is not often included in metabolomics studies. This is partly due to the lack of a community platform that provides structural information based on INADEQUATE. Also, it is often the case that a single study uses various NMR experiments synergistically to improve the quality of information or balance total NMR experiment time, but there is no public platform that can integrate the outputs of INADEQUATE with other NMR experiments. Here, we introduce PyINETA, a Python-based INADEQUATE network analysis. PyINETA is an open-source platform that provides structural information on molecules using INADEQUATE, conducts database searches using an INADEQUATE library, and integrates information on INADEQUATE and a complementary NMR experiment 13C J-resolved experiment (13C-JRES). 13C-JRES was chosen because of its ability to efficiently provide relative quantification in a study of the 13C-enriched samples. Those steps are carried out automatically, and PyINETA keeps track of all the pipeline parameters and outputs, ensuring the transparency of annotation in metabolomics. Our evaluation of PyINETA using a model mouse study showed that PyINETA successfully integrated INADEQUATE and 13C-JRES. The results showed that 13C-labeled amino acids that were fed to mice were transferred to different tissues and were transformed to other metabolites. The distribution of those compounds was tissue-specific, showing enrichment of specific metabolites in the liver, spleen, pancreas, muscle, or lung. PyINETA is freely available on NMRbox.PMID:39563064 | DOI:10.1021/acs.analchem.4c03966

J Anim Sci. 2024 Nov 20:skae355. doi: 10.1093/jas/skae355. Online ahead of print.ABSTRACTThe ability to predict fresh pork tenderness and quality is hindered by an incomplete understanding of molecular factors that influence these complex traits. It is hypothesized that a comprehensive description of the metabolomic and proteomic phenotypes associated with variation in pork tenderness and quality will enhance the understanding and inform the development of rapid and non-destructive methods to measure pork quality. The objective of this investigation was to examine the proteomic and metabolomic profiles of approximately 2-week aged pork chops categorized across instrumental tenderness groups. One hundred pork loin chops from a larger sample (N=120) were assigned to one of four categories (n=25) based on instrumental star probe value. (Category A, x = 4.23 kg, 3.43-4.55 kg; Category B, x = 4.79 kg, 4.66-5.00 kg; Category C, x = 5.43 kg, 5.20-5.64 kg; Category D, x = 6.21 kg, 5.70-7.41 kg;). Soluble protein from approximately two week aged pork loin was prepared using a low ionic strength buffer. Proteins were digested with trypsin, labeled with 11-plex isobaric TMT reagents, and identified and quantified using a Q-Exactive Mass Spectrometer. Metabolites were extracted in 80 % methanol from lyophilized and homogenized tissue samples. Derivatized metabolites were identified and quantified using GC-MS. Between Categories A and D, 84 proteins and 22 metabolites were differentially abundant (Adjusted P < 0.05). Fewer differences were detected in comparison between categories with less divergent tenderness measures. The molecular phenotype of the more tender (Category A) aged chops is consistent with a slower and less extended pH decline and markedly less abundance of glycolytic metabolites. The presence and greater abundance of proteins in the low ionic strength extract, including desmin, filamin C, calsequestrin, and fumarate hydratase, indicates a greater disruption of sarcoplasmic reticulum and mitochondrial membranes and the degradation and release of structural proteins from the continuous connections of myofibrils and the sarcolemma.PMID:39563021 | DOI:10.1093/jas/skae355

Pediatr Res. 2024 Nov 19. doi: 10.1038/s41390-024-03728-w. Online ahead of print.ABSTRACTThe rapid and accurate diagnosis of rare diseases is paramount in directing clinical management. In recent years, the integration of multi-omics approaches has emerged as a potential strategy to overcome diagnostic hurdles. This review examines the application of multi-omics technologies, including genomics, epigenomics, transcriptomics, proteomics, and metabolomics, in relation to the diagnostic journey of rare diseases. We explore how these combined approaches enhance the detection of pathogenic genetic variants and decipher molecular mechanisms. This review highlights the groundbreaking potential of multi-omics in advancing the precision medicine paradigm for rare diseases, offering insights into future directions and clinical applications. IMPACT: This review discusses using current tests and emerging technologies to diagnose pediatric rare diseases. We describe the next steps after inconclusive molecular testing and a structure for using multi-omics in further investigations. The use of multi-omics is expanding, and it is essential to incorporate it into clinical practice to enhance individualized patient care.PMID:39562738 | DOI:10.1038/s41390-024-03728-w

Nat Commun. 2024 Nov 19;15(1):10003. doi: 10.1038/s41467-024-54392-x.ABSTRACTHeavy metal contamination poses an escalating global challenge to soil ecosystems, with hyperaccumulators playing a crucial role in environmental remediation and resource recovery. The enrichment of diazotrophs and resulting nitrogen accumulation promoted hyperaccumulator growth and facilitated phytoremediation. Nonetheless, the regulatory mechanism of hyperaccumulator biological nitrogen fixation has remained elusive. Here, we report the mechanism by which arsenic regulates biological nitrogen fixation in the arsenic-hyperaccumulator Pteris vittata. Field investigations and greenhouse experiments, based on multi-omics approaches, reveal that elevated arsenic stress induces an enrichment of key diazotrophs, enhances plant nitrogen acquisition, and thus improves plant growth. Metabolomic analysis and microfluidic experiments further demonstrate that the upregulation of specific root metabolites plays a crucial role in recruiting key diazotrophic bacteria. These findings highlight the pivotal role of nitrogen-acquisition mechanisms in the arsenic hyperaccumulation of Pteris vittata, and provide valuable insights into the plant stress resistance.PMID:39562570 | DOI:10.1038/s41467-024-54392-x

Methods Mol Biol. 2024;2788:C1-C2. doi: 10.1007/978-1-0716-3782-1_24.NO ABSTRACTPMID:39562475 | DOI:10.1007/978-1-0716-3782-1_24

Carbohydr Polym. 2025 Jan 15;348(Pt A):122779. doi: 10.1016/j.carbpol.2024.122779. Epub 2024 Sep 25.ABSTRACTA water-insoluble β-1,3-glucan (Wβ) with a molecular weight of 8.12 × 104 Da was extracted from an edible fungus Wolfiporia cocos. Its backbone was composed of 1,3-β-linked Glcp branched at the C-2, C-4, and C-6 positions, connecting more 1,3-β-linked Glcp with a triple helical structure. Wβ effectively ameliorated depressive symptoms, abnormality of neurotransmitters and inflammatory factors in chronic unpredictable mild stress (CUMS)-induced rats. Wβ also altered the composition of gut microbiota, especially Romboutsia, norank_f_Muribaculaceae and Ruminococcus. Integration of untargeted and targeted metabolomics and Western blotting analysis suggested that the short-chain fatty acids (SCFAs) and tryptophan metabolites were the most important metabolites involved in Wβ mediation. Wβ significantly modulated the levels of 7 SCFAs and 7 tryptophan metabolites, as well as the protein expression of two related enzymes (indoleamine-2,3-dioxygenase: IDO; kynurenine-3-monooxygenase: KMO). Our results suggest that Wβ exerts its antidepressant effect by influencing neurotransmitters and inflammatory factors through interactions between the gut microbiota, SCFA and tryptophan metabolites. The findings offer new insights into water-insoluble polysaccharides, especially β-glucan in structure analysis and utilization, and provide evidence that Wβ, a novel glucan from the often-discarded water-insoluble part of Wolfiporia cocos, has potential application in antidepressant health products.PMID:39562060 | DOI:10.1016/j.carbpol.2024.122779

Gene. 2024 Nov 17:149106. doi: 10.1016/j.gene.2024.149106. Online ahead of print.ABSTRACTRheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation and joint destruction, with emerging evidence implicating gut microbiota dysbiosis in its pathogenesis. The current study explores the role of ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, in modulating gut microbiota and metabolic dysregulation through the enzyme peptidyl arginine deiminase 4 (PAD4) in collagen-induced arthritis (CIA) mouse model. Our findings demonstrate that ferroptosis exacerbates RA-related inflammatory responses and joint damage by upregulating PAD4 expression, which, in turn, influences the gut microbial composition and associated metabolite profiles. Erastin, a known ferroptosis agonist, significantly increased the relative abundance of pro-inflammatory bacteria such as Proteobacteria while reducing beneficial taxa like Firmicutes and Bacteroidetes. This microbial shift was associated with heightened oxidative stress and an imbalance in key metabolites, such as lysophosphatidyl ethanolamine 14:0 (LysoPE 14:0), further exacerbated by ferroptosis. Co-treatment with GSK484, a PAD4 inhibitor, reversed these effects, restoring microbial homeostasis and reducing joint inflammation. This study suggests that ferroptosis-mediated PAD4 activity contributes to RA pathogenesis by disrupting the gut-joint axis, providing novel insights into potential therapeutic targets for RA. Our results highlight the intricate interplay between immune-mediated cell death, gut microbiota, and systemic inflammation, emphasizing the importance of ferroptosis as a therapeutic target in mitigating RA progression.PMID:39561902 | DOI:10.1016/j.gene.2024.149106

J Proteomics. 2024 Nov 17:105357. doi: 10.1016/j.jprot.2024.105357. Online ahead of print.ABSTRACTRenal cell carcinoma (RCC) stands among the most lethal urological malignancies. Most RCCs are incidentally diagnosed as initial symptoms are unspecific. Novel, minimally-invasive diagnostic and prognostic methods for RCC are needed, ideally in urine. Using UPLC-Q-ToF MS untargeted metabolomic analysis in urine, we previously revealed p-cresol glucuronide as potential RCC diagnostic marker. Additionally, urine samples one-year post-nephrectomy revealed isobutyryl-l-carnitine and L-proline betaine as potential RCC prognostic markers. Our present aim was to validate these differences in an independent cohort of RCC patients and healthy controls to strengthen their value as non-invasive biomarkers. In an independent cohort of 69 RCC patients and 52 controls we validated an increase in p-cresol glucuronide in urine from patients at diagnosis compared to controls (P = 0.0043). It remained increased one-year post-nephrectomy (P = 0.0288). The value of p-cresol glucuronide for RCC diagnosis was assessed with ROC curves analysis (AUC = 0.66, 95 % Confidence Interval 0.56-0.76). The role of isobutyryl-l-carnitine and L-proline betaine as prognostic markers could not be validated and will require a larger cohort. Our findings confirm the value of p-cresol glucuronide in urine as diagnostic marker for RCC in an independent cohort. This non-invasive method holds promise for enhancing patient care by reducing the need for potentially risky diagnostic procedures. Further metaproteomics-oriented approaches towards the tyrosine oxidation pathway and microbiota metagenomics studies may promote a holistic management of RCC. SIGNIFICANCE: Current imaging techniques available to diagnose and monitor renal cell carcinoma (RCC) are harmful for the patient given the high-radiation dose, and unspecific in low-grade tumors. Thus, novel non-invasive biomarkers with diagnostic and prognostic capabilities are of utmost importance. Herein, we have validated urine p-cresol glucuronide as diagnostic marker for RCC. This novel non-invasive biomarker could improve accurate assessments of tumor behavior, while enhancing patient outcomes by reducing discomfort and detrimental side effects.PMID:39561853 | DOI:10.1016/j.jprot.2024.105357

Redox Biol. 2024 Nov 9;78:103422. doi: 10.1016/j.redox.2024.103422. Online ahead of print.ABSTRACTTime-restricted eating (TRE) has been shown to extent lifespans in drosophila and mouse models by affecting metabolic and anti-inflammatory activities. However, the effect of TRE on the human immune system, especially on immunosenescence, intestinal microbiome, and metabolism remains unclear. We conducted a 30-day 16:8 TRE single-arm clinical trial with 49 participants. Participants consumed daily meals from 9 a.m. to 5 p.m., provided by a nutrition canteen with a balanced, calorie-appropriate nutrition, which is designed by clinical nutritionists (ChiCTR2200058137). We monitored weight changes and weight-related parameters and focused on changes in the frequency of CD4+ senescent T cells, immune repertoire from peripheral blood, as well as serum metabolites and gut microbiota. We found that up to 95.9 % of subjects experienced sustained weight loss after TRE. The frequency of circulating senescent CD4+ T cells was decreased, while the frequency of Th1, Treg, Tfh-like, and B cells was increased. Regarding the immune repertoire, the proportions of T cell receptor alpha and beta chains were increased, whereas B cell receptor kappa and lambda chains were reduced. In addition, a reduced class switch recombination from immunoglobulin M (IgM) to immunoglobulin A (IgA) was observed. TRE upregulated the levels of anti-inflammatory and anti-aging serum metabolites named sphingosine-1-phosphate and prostaglandin-1. Additionally, several anti-inflammatory bacteria and probiotics were increased, such as Akkermansia and Rikenellaceae, and the composition of the gut microbiota tended to be "younger". Overall, TRE showed multiple anti-aging effects, which may help humans maintain a healthy lifestyle to stay "young". Clinical Trial Registration URL: https://www.chictr.org.cn/showproj.html?proj=159876.PMID:39561680 | DOI:10.1016/j.redox.2024.103422

Phytomedicine. 2024 Nov 8;135:156223. doi: 10.1016/j.phymed.2024.156223. Online ahead of print.ABSTRACTBACKGROUND: Liver fibrosis is a dynamic process marked by the accumulation of extracellular matrix due to hepatic stellate cells (HSCs) activation. Ginsenoside compound K (CK), a rare derivative of its parent ginsenosides, is known to significantly ameliorate metabolic disorders.PURPOSE: The aim of this study was to elucidate the protective effects of CK against liver fibrosis with a focus on metabolic regulation.METHODS: We established liver fibrosis models in mice using carbon tetrachloride (CCl4) challenge, bile duct ligation, or a methionine-choline deficient diet, with continuous oral administration of CK at specified doses and intervals. Simultaneously, we examined the impact of CK on metabolic regulation in cultured HSCs and investigated the associated mechanisms.RESULTS: CK was found to alleviate liver injury and curb fibrotic responses in mouse models, as well as decrease elevated levels of liver enzyme. Metabolomic analysis in vitro highlighted the crucial roles of pyruvate and glutamine metabolism in metabolic remodeling. Immunohistochemical staining indicated significantly elevated expressions of lactate dehydrogenase A (LDHA) (p = 0.014) and glutaminase 1 (GLS1) (p = 0.024) in liver cirrhosis patients. Comparable alterations were noted in the liver of model mice and in cultured HSCs. Molecular docking and bio-layer interferometry demonstrated that CK interacts with and inhibits the activities of LDHA and GLS1. As expected, CK attenuated glycolysis and glutaminolysis, reducing HSC growth dependently on lactate and α-ketoglutarate (α-KG). Upon HSC activation, metabolism is reprogrammed with Myc as a key regulator, transcriptionally controlling LDHA, GLS1, and glutamine transporters SLC1A5 and SLC38A5. CK inhibited Myc induction, integrating glycolysis and glutaminolysis regulation to counteract the fibrotic response.CONCLUSION: CK inhibited LDHA and GLS1 activities, thereby inhibiting hepatic fibrosis. These findings offer new insights into the role of ginsenosides in liver protection, especially regarding metabolic disorders.PMID:39561660 | DOI:10.1016/j.phymed.2024.156223

Aquat Toxicol. 2024 Nov 13;277:107164. doi: 10.1016/j.aquatox.2024.107164. Online ahead of print.ABSTRACTNitrite is a toxic substance found in rearing water that affects shrimp health. The hepatopancreas is an important digestive, immune, and metabolic organ in the shrimp. In this study, shrimps (Litopenaeus vannamei) were separately exposed to 1 and 5 mg/L nitrite stress for 48 h, and the toxicity of nitrite in the hepatopancreas was explored by integrating histology, physiological indicators, energy metabolism, and metabolomics. Nitrite stress induced morphological changes and stress responses in the hepatopancreas. Specifically, physiology-related indices, such as the relative gene expression levels of antioxidants (ROMO1, Nrf2, GPx), endoplasmic reticulum stress (Bip, IRE1 and XBP1), and immune genes (ALF, Pen-3, Lys) were decreased, whereas the gene expression of apoptosis (Casp-3), detoxification (CYP450), and glutamic oxaloacetic transaminase (GOT) activity were increased. The activities of osmotic adjustment-related enzymes (NKA, CMA, and ATPase) also decreased. Energy metabolism-related indices, such as pyruvate and hepatic glycogen contents, increased, whereas glucose, lactic acid, triglyceride, and ATP contents and ATPase activity decreased, and the relative gene expression levels of carbohydrate metabolism (PDH, HK, and LDH) and electron-transport chain genes (CytC, COI and CCO) decreased, and the expressions of lipid metabolism (AMPK, SREBP, and FAS), tricarboxylic acid cycle (MDH, CS, IDH and FH) genes were also disturbed. The metabolic pattern of the hepatopancreas was affected by nitrite stress. Glycine, serine, and threonine metabolism were highly affected, and more functional amino acids varied in the 5 mg/L nitrite stress group. These results reveal the toxic effects of nitrite stress on the stress response, physiology, energy metabolism, and metabolite homeostasis in the hepatopancreas of shrimp. Several potential metabolite biomarker candidates were identified for toxicological evaluation.PMID:39561610 | DOI:10.1016/j.aquatox.2024.107164

J Hazard Mater. 2024 Nov 12;481:136470. doi: 10.1016/j.jhazmat.2024.136470. Online ahead of print.ABSTRACTTo reveal the disruption caused by herbicides and the mechanisms of algal interactions on interspecific competitive strategies at a metabolic and population level, this study established short-term (7 d) and long-term (21 d) Scenedesmus-Microcystis competition coculture systems and investigated the toxicity of acetochlor (ACT) on algae competition. Scenedesmus obliquus (EC50 6.586 μg/L) is three orders of magnitude more sensitive to ACT than Microcystis aeruginosa (EC50 19,539 μg/L), placing it at a competitive disadvantage in environments with ACT pollution. Short-term coculture tests (ACT concentrations from 0 to 12.5 μg/L) showed that ACT suppresses S. obliquus growth and competition, while M. aeruginosa initially showed compensatory growth, which was negated by ACT. Metabolomics revealed that interspecies competition and ACT affect fatty acid synthesis and nitrogen assimilation metabolism of both microalgae, suggesting species differences in the mode of action (MOA) of ACT toxicity and resource competition strategies, respectively. ACT weakens the ability of M. aeruginosa to compete for nitrogen and synthesize microcystin under competitive stress. ACT biotransformation can be conducted across species. In an algal culture system with equal initial biomass, the 7 d ACT degradation rate increased by 24.9 % and 123.8 % with coculture of the two algae compared with monocultures of S. obliquus and M. aeruginosa, respectively. In long-term experiments, the degradation rate increased by 19.0 % and 8.9 % in cocultures compared with the monocultures. Lotka-Volterra models showed that competitive inhabitation was alleviated, implying that the competition interspecies relationship is beneficial for the coexistence of both algal populations under ACT stress.PMID:39561538 | DOI:10.1016/j.jhazmat.2024.136470

J Neurol Sci. 2024 Nov 10;467:123303. doi: 10.1016/j.jns.2024.123303. Online ahead of print.ABSTRACTThe study examined changes in the plasma proteome, metabolome, and lipidome of N = 14 patients with relapsing-remitting multiple sclerosis (RRMS) initiating treatment with ocrelizumab, assayed at baseline, 6 months, and 12 months. Analyses of >4000 circulating biomarkers identified depletion of B-cell associated proteins as the early effect observed following ocrelizumab (OCR) initiation, accompanied by the reduction in plasma abundance of cytokines and cytotoxic proteins, markers of neuronaxonal damage, and biologically active lipids including ceramides and lysophospholipids, at 6 months. B-cell depletion was accompanied by decreases in B-cell receptor and cytokine signaling but a pronounced increase in circulating plasma B-cell activating factor (BAFF). This was followed by an upregulation of a number of signaling and metabolic pathways at 12 months. Patients with higher baseline brain MRI lesion load demonstrated both higher levels of cytotoxic and structural proteins in plasma at baseline and more pronounced biomarker change trajectories over time. Digital cytometry identified a putative increase in myeloid cells and a pro-inflammatory subset of T-cells. Therapeutic effects of ocrelizumab extend beyond CD20-mediated B-cell lysis and implicate metabolic reprogramming, juxtaposing the early normalization of immune activation, cytokine signaling and metabolite and lipid turnover in periphery with changes in the dynamics of immune cell activation or composition. We identify BAFF increase following CD20 depletion as a tentative compensatory mechanism that contributes to the reconstitution of targeted B-cells, necessitating further research.PMID:39561535 | DOI:10.1016/j.jns.2024.123303

J Chromatogr B Analyt Technol Biomed Life Sci. 2024 Nov 13;1249:124372. doi: 10.1016/j.jchromb.2024.124372. Online ahead of print.ABSTRACTSymptoms of ulcerative colitis (UC) are like "intestinal carbuncle" in Chinese medicine. The aqueous extract of Sargentodoxa cuneata (AESc) has good therapeutic effects on UC, but the underlying mechanism needs to be further elucidated. The mechanism of AESc against UC was studied based on metabolomics and bioinformatics in mice with UC. Dextran sodium sulfate was applied to induce a mouse model of UC. After the intervention of AESc, the general condition of the animals was recorded, and efficacy-related indicators were measured. Information on serum metabolites was determined. Multivariate analysis combined with bioinformatics methods were used to identify the differential metabolites. Furthermore, "metabolite-target-disease" network was obtained, and differential metabolites of UC were screened, and further analysis of the metabolites were performed. Molecular docking validation was also carried out. AESc improved general conditions such as blood in stool, hair of animals, and weight loss, reduced disease activity index scores and shortening of colon length in mice with UC. A total of 3445 serum metabolites were obtained, and 64 differentiated metabolites of AESc against UC were screened. Enrichment analysis showed that arachidonic acid metabolism, bile secretion, drug metabolism-other enzymes, and tyrosine metabolism were associated with AESc in the treatment of UC. In addition, based on "metabolite-target-disease" network, the serum metabolites cholylleucine, 9,10,13-TriHOME, birabresib, anthramycin methyl ether, trans-hexadec-2-enoyl carnitine, and lucidumol A were found to have the therapeutic potential for UC. Further, 14 core targets were obtained, and lipids and atherosclerosis, rheumatoid arthritis and multiple immune-inflammatory pathways were associated with AESc for the treatment of UC. AESc corrects serum metabolic disturbances in UC mice, and multiple serum metabolites have therapeutic potential for UC. AESc may treat UC by regulating biological processes such as lipid metabolism, amino acid metabolism, thereby restoring normal physiological function of the intestine.PMID:39561468 | DOI:10.1016/j.jchromb.2024.124372

G3 (Bethesda). 2024 Nov 19:jkae195. doi: 10.1093/g3journal/jkae195. Online ahead of print.ABSTRACTPeppermint, Mentha × piperita L., is a hexaploid (2n = 6x = 72) and the predominant cultivar of commercial mint oil production in the US. This cultivar is threatened because of high susceptibility to the fungal disease verticillium wilt, caused by Verticillium dahliae. This report details the first draft polyploid chromosome-level genome assembly for this mint species. The "Mitcham" genome resource will broaden comparative studies of disease resistance, essential oil biosynthesis, and hybridization events within the genus Mentha. It will also be a valuable contribution to the body of phylogenetic studies involving Mentha and other genera that contain species with varying ploidy levels.PMID:39561240 | DOI:10.1093/g3journal/jkae195

Cell Rep. 2024 Nov 18;43(11):114976. doi: 10.1016/j.celrep.2024.114976. Online ahead of print.ABSTRACTCore components of the N-glycosylation pathway are known, but the metabolic and post-translational mechanisms regulating this pathway in normal and disease states remain elusive. Using a multi-omic approach in zebrafish, we discovered a mechanism whereby O-GlcNAcylation directly impacts the expression and abundance of two rate-limiting proteins in the N-linked glycosylation pathway. We show in a model of an inherited glycosylation disorder PMM2-CDG, congenital disorders of glycosylation that phosphomannomutase deficiency is associated with increased levels of UDP-GlcNAc and protein O-GlcNAcylation. O-GlcNAc modification increases the transcript and protein abundance of both NgBR and Dpagt1 in pmm2m/m mutants. Modulating O-GlcNAc levels, NgBR abundance, or Dpagt1 activity exacerbated the cartilage phenotypes in pmm2 mutants, suggesting that O-GlcNAc-mediated increases in the N-glycosylation machinery are protective. These findings highlight nucleotide-sugar donors as metabolic sensors that regulate two spatially separated glycosylation pathways, demonstrating how their coordination is relevant to disease severity in the most common congenital disorder of glycosylation.PMID:39561044 | DOI:10.1016/j.celrep.2024.114976

Nutr Neurosci. 2024 Nov 19:1-12. doi: 10.1080/1028415X.2024.2425565. Online ahead of print.ABSTRACTThe relevance of lifestyle, including diet and exercise, has been associated with improved learning and memory capacity, delayed age-related cognitive decline, and a reduced risk of neurodegeneration. Most neurodegenerative diseases are defined as complex multifactorial disorders in which genetic and environmental factors greatly contribute to their onset. Although inflammatory cells produce reactive oxygen species (ROS), oxidative stress itself might exert pro-inflammatory effects and an uncontrolled response could lead to a state of chronic inflammation. Anti-inflammatory dietary approaches unify the disciplines of nutrition, immunity, and neurology. Personalized dietary interventions will be developed based on an individual's genetic makeup, metabolic profile, and gut microbiota composition, thanks to advances in genomics, metabolomics, and microbiome research. The relevance of dietary patterns in decreasing inflammation relies on the role of specific antioxidant nutrients, which might contribute to a decrease in the levels of ROS. This review aims to summarize recent advancements in neuroscience and immunology that have revealed the crucial role that diet and the immune system play in brain function and disease progression. Nutrition influences the immune system, and in turn, the immune system impacts neurological health. This bidirectional relationship suggests that targeted nutritional interventions could modulate immune responses to delay or mitigate the progression of neurodegenerative diseases potentially. This approach focuses on the use of specific nutrients and dietary components that influence the immune system and inflammatory pathway. Key elements of immunonutrition include omega-3 fatty acids, antioxidants, vitamins and various bioactive compounds found in foods.PMID:39561029 | DOI:10.1080/1028415X.2024.2425565

Environ Sci Technol. 2024 Nov 19. doi: 10.1021/acs.est.4c07188. Online ahead of print.ABSTRACTTire wear particles (TWPs), generated from tire abrasion, contribute significantly to environmental contamination. The toxicity of TWPs to organisms has raised significant concerns, yet their effects on terrestrial plants remain unclear. Here, we investigated the long-term impact of pristine and naturally aged TWPs on water spinach (Ipomoea aquatica) and its rhizospheric soil. The results indicated that natural aging reduced the toxicity of TWPs, as evidenced by decreased levels of polycyclic aromatic hydrocarbons (PAHs) in soil and TWPs themselves. Consequently, aged TWPs were found to enhance the plant growth and chlorophyll content, whereas pristine TWPs increased the plant stress. Furthermore, aged TWPs improved soil organic matter (SOM) and total organic carbon (TOC), thereby boosting the microbial enzymes involved in nitrogen cycling. Metabolomic analysis revealed that aged TWPs upregulated key pathways related to carbon and nitrogen metabolism, enhancing plant growth and stress responses. Additionally, rhizosphere bacterial diversity was higher under aged TWPs, favoring nutrient-cycling taxa such as Acidobacteriota and Nitrospirota. Pristine TWPs may lead to overproliferation of certain dominant species, thereby reducing microbial diversity in soil, which could ultimately compromise the soil health. These findings contribute to a deeper understanding of the mechanisms underlying TWP toxicity in plants and highlight the necessity for further research on the impact of aged TWPs across various plant species over different exposure durations for comprehensive risk assessment.PMID:39561015 | DOI:10.1021/acs.est.4c07188

J Clin Invest. 2024 Nov 19:e177824. doi: 10.1172/JCI177824. Online ahead of print.ABSTRACTThe glioblastoma (GBM) microenvironment is enriched in immunosuppressive factors that potently interfere with the function of cytotoxic T lymphocytes. Cancer cells can directly impact the immune system, but the mechanisms driving these interactions are not completely clear. Here we demonstrate that the polyamine metabolite spermidine (SPD) is elevated in the GBM tumor microenvironment. Exogenous administration of SPD drives tumor aggressiveness in an immune-dependent manner in pre-clinical mouse models via reduction of CD8+ T cell frequency and reduced cytotoxic function. Knockdown of ornithine decarboxylase, the rate-limiting enzyme in spermidine synthesis, did not impact cancer cell growth in vitro but did result in extended survival. Furthermore, glioblastoma patients with a more favorable outcome had a significant reduction in spermidine compared to patients with a poor prognosis. Our results demonstrate that spermidine functions as a cancer cell-derived metabolite that drives tumor progression by reducing CD8+ T cell number and function.PMID:39561012 | DOI:10.1172/JCI177824

Arch Gynecol Obstet. 2024 Nov 19. doi: 10.1007/s00404-024-07828-0. Online ahead of print.ABSTRACTThere is a general lack of awareness regarding how the mode of delivery can significantly influence the omics composition of biological samples such as umbilical cord blood and amniotic fluid. To address this, we analyzed the impact of delivery mode on proteomic and metabolomic profiles in a cohort of 40 healthy pregnant women without complications, including 16 who had vaginal delivery (VD), 16 who underwent elective cesarean delivery by maternal request (CS), and 8 who had intrapartum cesarean section (Intra_CS). Using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) for proteomic and untargeted metabolomic analyses, we compared amniotic fluid and cord blood samples across delivery modes. The amniotic fluid proteomic and metabolomic profiles of CS women exhibited clear separation from those of VD individuals, whereas only the proteomic profiles of the Intra_CS group differed when compared to the CS group. In cord blood, metabolomic profiles differed between CS and VD women, but proteomic profiles showed no separation. These findings highlight the significant impact of delivery mode on omics profiles, particularly amniotic fluid proteomics and metabolomics, and cord blood metabolomics. Larger studies are needed to validate these findings and expand their generalizability to broader populations.PMID:39560725 | DOI:10.1007/s00404-024-07828-0