PubMed
The role of urine metabolomics in the diagnosis and management of adult and pediatric Crohn's disease and ulcerative colitis
Biomarkers. 2024 Dec 6:1-15. doi: 10.1080/1354750X.2024.2438734. Online ahead of print.ABSTRACTINTRODUCTION: Urine metabolomics offers a non-invasive approach to diagnose and manage inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), by identifying distinct metabolic signatures.OBJECTIVES: This narrative review summarizes current findings on urinary metabolites in IBD, evaluating their roles in disease differentiation, assessment of activity, and monitoring therapeutic response.METHODS: A comprehensive literature search of PubMed and MEDLINE up to October 2023 was conducted using keywords such as "urine metabolomics," "inflammatory bowel disease," "Crohn's disease," "ulcerative colitis," and "urinary biomarkers." Studies were included that described alterations to metabolic pathways, including those related to the urea cycle, central energy metabolism (Krebs cycle), amino acid metabolism, and neurotransmitters.RESULTS: Specific urinary metabolites differentiate IBD patients from healthy controls and between CD and UC. Decreased urinary levels of hippurate, acetate, methanol, formate, and methylamine are observed in IBD, indicating altered gut microbiota. In CD patients, urea cycle alterations include reduced urinary urea and ornithine with increased arginine. Changes in Krebs cycle intermediates show decreased citrate and succinate in adults, but increased fumarate and isocitrate in pediatric patients, reflecting energy metabolism differences. Amino acid metabolism differs by age: adults exhibit decreased urinary asparagine, lysine, and histidine, while pediatric patients show increased methionine, proline, aspartic acid, and isoleucine. Elevated urinary neurotransmitters like dopamine are noted in pediatric IBD patients. Urine metabolomics also can monitor treatment efficacy by distinguishing responders from non-responders to therapies and differentiating active disease from remission.CONCLUSION: Urine metabolomics provides promising, non-invasive biomarkers to enhance IBD diagnostics by distinguishing CD from UC and offering insights into underlying metabolic disturbances, paving the way for more precise, accessible patient care.PMID:39642943 | DOI:10.1080/1354750X.2024.2438734
Nuclear GTPSCS functions as a lactyl-CoA synthetase to promote histone lactylation and gliomagenesis
Cell Metab. 2024 Dec 4:S1550-4131(24)00451-0. doi: 10.1016/j.cmet.2024.11.005. Online ahead of print.ABSTRACTHistone lysine lactylation is a physiologically and pathologically relevant epigenetic pathway that can be stimulated by the Warburg effect-associated L-lactate. Nevertheless, the mechanism by which cells use L-lactate to generate lactyl-coenzyme A (CoA) and how this process is regulated remains unknown. Here, we report the identification of guanosine triphosphate (GTP)-specific SCS (GTPSCS) as a lactyl-CoA synthetase in the nucleus. The mechanism was elucidated through the crystallographic structure of GTPSCS in complex with L-lactate, followed by mutagenesis experiments. GTPSCS translocates into the nucleus and interacts with p300 to elevate histone lactylation but not succinylation. This process depends on a nuclear localization signal in the GTPSCS G1 subunit and acetylation at G2 subunit residue K73, which mediates the interaction with p300. GTPSCS/p300 collaboration synergistically regulates histone H3K18la and GDF15 expression, promoting glioma proliferation and radioresistance. GTPSCS represents the inaugural enzyme to catalyze lactyl-CoA synthesis for epigenetic histone lactylation and regulate oncogenic gene expression in glioma.PMID:39642882 | DOI:10.1016/j.cmet.2024.11.005
Microbiota-derived short-chain fatty acids determine stem cell characteristics of gastric chief cells
Dev Cell. 2024 Nov 27:S1534-5807(24)00672-5. doi: 10.1016/j.devcel.2024.11.007. Online ahead of print.ABSTRACTThe gastric mucosa is a highly dynamic tissue that undergoes constant self-renewal through stem cell differentiation. Chief cells maintain a quiescent state in homeostasis but are responsible for regeneration after injury. Although the role of microbiome-host interactions in the intestine is well studied, less is known about these interactions in the stomach. Using the mouse organoid and germ-free mouse models, we show that microbiota-derived short-chain fatty acids (SCFAs) suppress the proliferation of chief cells in mice. This effect is mediated by activation of G-protein-coupled receptor 43. Most importantly, through metabolomics and transplantation studies, we show butyrate-producing Lactobacillus intestinalis modulates the proliferation of chief cells in mice. Our findings identify a mechanism by which the microbiota regulates the cell characteristics of chief cells, providing insight into the complex interplay between the host and its microbial environment and the mechanisms underlying gastric homeostasis, with potential therapeutic implications for gastric diseases.PMID:39642880 | DOI:10.1016/j.devcel.2024.11.007
Distinct dynamic regulation of pectoralis muscle metabolomics by insulin and the promotion of glucose-lipid metabolism with extended duration
Poult Sci. 2024 Dec 2;104(1):104619. doi: 10.1016/j.psj.2024.104619. Online ahead of print.ABSTRACTBirds' glycolipid metabolism has garnered considerable attention due to their fasting blood glucose levels being nearly twice those of mammals. While skeletal muscle is the primary insulin-sensitive tissue in mammals, the effects of insulin on chicken skeletal muscle remain unclear. In this study, the insulin-responsive metabolites were identified in broiler's pectoralis muscle (after 16 h of fasting) using widely targeted metabolomics. Glycolipid concentrations were measured using kits, and the expression of key genes involved in glucose metabolism was assessed via quantitative real-time PCR (qRT-PCR). The insulin tolerance test, performed by injecting 5 IU/kg body weight of insulin, demonstrated a rapid drop in blood glucose levels from 0 to 15 min, with a consistent reduction observed at 120 min (P < 0.01). Insulin did not alter glucose and glycogen content in chicken pectoralis; however, low-density lipoprotein (LDL, P < 0.05) levels were upregulated in the early phase (15 min). With an extended insulin duration (120 min), pectoralis glucose content increased (P < 0.05), accompanied by a reduction in TG levels (P < 0.05). Metabolomic analysis revealed that insulin promotes the downregulation of 63 out of 71 metabolites at 15 min and the upregulation of 101 out of 134 metabolites at 120 min, mainly associated with lysine degradation and thyroid hormone signaling pathways, respectively. 7 metabolites were dynamically modulated in the same manner over time (2 up-up and 5 down-down). Early insulin inhibited glycolysis, evidenced by the reduction in phosphoenolpyruvate levels and hexokinase 2 (HK2) expression; however, insulin promoted glucose uptake through the activation of glucose transporter 4 (GLUT4) and enhanced glycolysis, accompanied by elevated fatty acid metabolism at the later phase. In conclusion, insulin dynamically regulates the metabolomics of the pectoralis muscle over time. Initially, chicken muscle tissues downregulate metabolic activities to accommodate the new signaling state, followed by significant upregulation to meet heightened metabolic demands. Extended insulin monitoring promotes glucose uptake and glycolysis, alongside enhanced fatty acid metabolism. This research provides insights into the potential mechanisms of insulin action in chicken muscles.PMID:39642750 | DOI:10.1016/j.psj.2024.104619
Chronic Exposure of Adult Zebrafish to Polyethylene and Polyester-based Microplastics: Metabolomic and Gut Microbiome Alterations Reflecting Dysbiosis and Resilience
J Hazard Mater. 2024 Nov 30;484:136691. doi: 10.1016/j.jhazmat.2024.136691. Online ahead of print.ABSTRACTThe study explored the ecotoxicological effects of chronic exposure to microplastic (MP) on adult zebrafish, focusing on environmentally relevant concentrations of polyethylene (PE) beads and polyester (PES). High-throughput untargeted metabolomics via UPLC-QToF-MS and 16S metagenomics for gut microbiota analysis were used to assess ecotoxicity in zebrafish exposed to varying concentrations of PE and PES. The VIP (Variable Importance in Projection) scores indicated PE exposure primarily impacted phospholipids, ceramides, and nucleotide-related compounds, while PES exposure led to alterations in lipid-related compounds, chitin, and amino acid derivatives. From MSEA (Metabolite Set Enrichment Analysis) and Mummichog analyses, PE and PES significantly disrupted key metabolomic pathways associated with inflammation, immune responses, and apoptosis, including leukotriene and arachidonic acid metabolism and the formation of putative anti-inflammatory metabolites from EPA. PE caused physical disruption and inflammation of the epithelial barrier, whereas PES affected gut microbiota interactions, impairing digestion and metabolism. Although alpha diversity within the gut microbiome remained stable, beta diversity analysis revealed significant shifts in microbial composition and structure, suggesting a disruption of functional balance and an increased susceptibility to pathogens. Chronic PE and PES exposures induced shifts in the gut microbial community and interaction network with potential increases in pathogenic bacteria and alteration in commensal bacteria, demonstrating the microbiome's resilience and adaptability to stressors of MPs exposure. High-throughput metabolomics and 16S metagenomics revealed potential chronic diseases associated with inflammation, immune system disorders, metabolic dysfunction, and gut dysbiosis, highlighting the complex relationship between gut microbiome resilience and metabolic disruption under MP-induced stress, with significant ecological implications.PMID:39642737 | DOI:10.1016/j.jhazmat.2024.136691
Applying newly suggested simultaneous analysis of metabolomics and lipidomics into perfluorooctanesulfonate-derived neurotoxicity mechanism in zebrafish embryos
J Hazard Mater. 2024 Nov 28;484:136712. doi: 10.1016/j.jhazmat.2024.136712. Online ahead of print.ABSTRACTDeveloping methodologies for performing multi-omics with one sample has been challenging in zebrafish toxicology; however, related studies are lacking. A new strategy for the simultaneous analysis of metabolomics and lipidomics in zebrafish embryos was proposed and applied to explore the neurotoxicity mechanisms of perfluorooctanesulfonate (PFOS). Metabolite and lipid profiled simultaneously with methyl tert-butyl ether (MTBE) were compared with individual results from other extraction solvents. Behavioral alterations were measured after the zebrafish embryos were exposed to 0.1-20 μM PFOS for 5 days. The metabolite-lipid profiles of the MTBE-based strategy analyzed with optimized larval pooling size of 30 were comparable to those of other extraction solvents, indicating the feasibility and efficiency of MTBE-based multi-omics analysis. Many metabolites and lipids, which were enriched more than those previously reported, completed the toxicity pathways involved in energy metabolism and sphingolipids, improving our understanding of PFOS-induced neurotoxicity mechanism manifested by increased movement under dark conditions. Our novel MTBE-based strategy enabled the multi-omics analysis of one sample with minimal use of zebrafish embryos, thereby improving data reliability on changes in multi-layered biomolecules. This study will advance multi-omics technologies that are critical to elucidating the toxicity mechanisms of toxic chemicals including per- and polyfluoroalkyl substances.PMID:39642725 | DOI:10.1016/j.jhazmat.2024.136712
A Comprehensive Guide to Volatolomics Data Analysis
J Breath Res. 2024 Dec 6. doi: 10.1088/1752-7163/ad9b46. Online ahead of print.ABSTRACTVolatolomics (or volatilomics), the study of volatile organic compounds, has emerged as a crucial field of metabolomics due
to its potential for non-invasive diagnostics and disease monitoring. However, analyzing high-resolution data generated by
mass spectrometry-based instrumentation remains challenging. This comprehensive guide provides an in-depth exploration
of volatolomics data analysis, highlighting the importance of subsequent steps, including data cleaning, pretreatment, and
statistical and machine learning techniques (dimensionality reduction, clustering, classification, and variable selection). The
choice of these methods, and the integration of data handling practices, such as missing data imputation, outlier detection,
model validation, and data integration, significantly impact the identification of meaningful metabolites and the accuracy of
diagnostic conclusions. This guide aims to familiarize the reader with the implications of various data analysis techniques in
volatolomics and their suitability for different applications. It emphasizes the necessity of understanding the strengths and
limitations of each method to make informed decisions that enhance the reliability of findings. By outlining these methodologies,
the guide aims to equip researchers with the knowledge needed to navigate the complexities of volatolomics data analysis. The
careful consideration of experimental design, data collection, and processing strategies is essential for the identification of
biomarkers, ultimately advancing the field and improving the understanding of metabolic processes in health and disease.PMID:39642393 | DOI:10.1088/1752-7163/ad9b46
A helminth enzyme subverts macrophage-mediated immunity by epigenetic targeting of prostaglandin synthesis
Sci Immunol. 2024 Dec 6;9(102):eadl1467. doi: 10.1126/sciimmunol.adl1467. Epub 2024 Dec 6.ABSTRACTThe molecular mechanisms by which worm parasites evade host immunity are incompletely understood. In a mouse model of intestinal helminth infection using Heligmosomoides polygyrus bakeri (Hpb), we show that helminthic glutamate dehydrogenase (heGDH) drives parasite chronicity by suppressing macrophage-mediated host defense. Combining RNA-seq, ChIP-seq, and targeted lipidomics, we identify prostaglandin E2 (PGE2) as a major immune regulatory mechanism of heGDH. The induction of PGE2 and other immunoregulatory factors, including IL-12 family cytokines and indoleamine 2,3-dioxygenase 1, by heGDH required p300-mediated histone acetylation, whereas the enzyme's catalytic activity suppressed the synthesis of type 2-promoting leukotrienes by macrophages via 2-hydroxyglutarate. By contrast, the induction of immunoregulatory factors involved the heGDH N terminus by potentially mediating interactions with cellular targets (CD64 and GPNMB) identified by proteomics. Type 2 cytokines counteracted suppressive effects of heGDH on host defense, indicating that type 2 immunity can limit helminth-driven immune evasion. Thus, helminths harness a ubiquitous metabolic enzyme to epigenetically target type 2 macrophage activation and establish chronicity.PMID:39642243 | DOI:10.1126/sciimmunol.adl1467
Correction: Urine metabolomic profiles of autism and autistic traits-A twin study
PLoS One. 2024 Dec 6;19(12):e0315559. doi: 10.1371/journal.pone.0315559. eCollection 2024.ABSTRACT[This corrects the article DOI: 10.1371/journal.pone.0308224.].PMID:39642154 | DOI:10.1371/journal.pone.0315559
Maternal obesity may disrupt offspring metabolism by inducing oocyte genome hyper-methylation via increased DNMTs
Elife. 2024 Dec 6;13:RP97507. doi: 10.7554/eLife.97507.ABSTRACTMaternal obesity has deleterious effects on the process of establishing oocyte DNA methylation; yet the underlying mechanisms remain unclear. Here, we found that maternal obesity disrupted the genomic methylation of oocytes using a high-fat diet (HFD) induced mouse model, at least a part of which was transmitted to the F2 oocytes and livers via females. We further examined the metabolome of serum and found that the serum concentration of melatonin was reduced. Exogenous melatonin treatment significantly reduced the hyper-methylation of HFD oocytes, and the increased expression of DNMT3a and DNMT1 in HFD oocytes was also decreased. These suggest that melatonin may play a key role in the disrupted genomic methylation in the oocytes of obese mice. To address how melatonin regulates the expression of DNMTs, the function of melatonin was inhibited or activated upon oocytes. Results revealed that melatonin may regulate the expression of DNMTs via the cAMP/PKA/CREB pathway. These results suggest that maternal obesity induces genomic methylation alterations in oocytes, which can be partly transmitted to F2 in females, and that melatonin is involved in regulating the hyper-methylation of HFD oocytes by increasing the expression of DNMTs via the cAMP/PKA/CREB pathway.PMID:39642055 | DOI:10.7554/eLife.97507
The immune mechanism of the mTOR/ACC1/CPT1A fatty acid oxidation signaling pathway in Hashimoto's thyroiditis
J Endocrinol Invest. 2024 Dec 6. doi: 10.1007/s40618-024-02501-4. Online ahead of print.ABSTRACTBACKGROUND: Hashimoto's thyroiditis (HT) is the most common autoimmune thyroid disease (AITD), which is distinguished by high thyroid peroxidase antibody (TPOAb) or thyroglobulin antibody (TgAb). The differentiation of CD4+T cell subsets in patients with HT is imbalanced, with Treg cells decreased and Th17 cells abnormally activated. Fatty acid oxidation supports the differentiation of Th17 cells and induces inflammation, but the specific mechanism is still unknown. This study aimed to explore the role of fatty acid oxidation and its pathway in the pathogenesis of autoimmune thyroiditis and the immune mechanism.METHODS: In in vitro experiments, a total of 60 HT patients and 20 healthy controls were selected and their CD4+T cells were sorted by magnetic beads. All 80 samples were divided into 4 groups on average: HC group (Healthy control group), HT group (Hashimoto thyroiditis CD4+T cell inactive group), TCC group(Hashimoto thyroiditis CD4+T cell activation), TCC + ETO group(Hashimoto thyroiditis CD4+T cell activation + Etomoxir group). In in vivo experiments, the mice were randomly divided into 3 groups: Con group(Control group), mTg group (CBA/J mice were injected with mTg for modeling, that is EAT mice group), and mTg + ETO group (Etomoxir intervention in EAT mice group). Fatty acid oxidation substrates of CD4+T cells in human peripheral blood were detected by targeted metabolomics. The expressions of key fatty acid oxidation proteins mTOR, ACC1 and CPT1A were detected by Western blotting. The proportion of CD4+T cell subtype differentiation in human and mouse models was detected by flow cytometry. The severity of EAT was detected by HE staining.RESULTS: Compared with healthy controls, the level of CPT1A in CD4+T cells of HT patients was increased, and the intracellular fatty acid content was significantly decreased, indicating that the level of fatty acid oxidation was enhanced in HT patients. After adding Etomoxir, the level of fatty acid oxidation was significantly inhibited, and the imbalance of CD4+T cell subpopulation differentiation in HT patients was reversed. In EAT mice, the mTOR/ACC1/CPT1A pathway was significantly activated, and its expression level was decreased after adding Etomoxir. At the same time, Etomoxir could reverse the reprogramming of abnormal metabolism in EAT mice cells, reduce the spleen index, and improve lymphocyte infiltration in the thyroid.CONCLUSIONS: The mTOR/ACC1/CPT1A fatty acid oxidation pathway of CD4+T cells in Hashimoto's thyroiditis was increased, and treatment with Etomoxir could inhibit the activation of this pathway, and reverse the reprogramming of abnormal metabolism in CD4+T cells, thereby reducing Hashimoto's thyroiditis.PMID:39641893 | DOI:10.1007/s40618-024-02501-4
Mendelian randomization study of causal link from Cerebrospinal fluid metabolomics to neurodegenerative diseases
Neurogenetics. 2024 Dec 6;26(1):15. doi: 10.1007/s10048-024-00792-6.ABSTRACTTo investigate the causal relationships between cerebrospinal fluid (CSF) metabolites and various neurodegenerative diseases (NDDs), we conducted a two-sample Mendelian randomization (MR) analysis. This study utilized summary statistics from genome-wide association studies (GWAS) of CSF metabolites and four common neurodegenerative diseases: Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). MR methods were employed to determine causal associations, with the inverse variance weighted method as the primary approach. Additionally, different GWAS summary data for NDDs were used to validate the initial results and perform sensitivity analyses to enhance the robustness of the findings. Finally, reverse MR analyses were conducted to assess the possibility of reverse causation. Combining results from the initial and replication phases of MR analysis, we identified potential causal relationships between various CSF metabolites and different NDDs. Specifically, we found potential causal relationships between five CSF metabolites and AD, six CSF metabolites and MS, and thirteen CSF metabolites and ALS. Further sensitivity analyses confirmed the robustness of these associations. Reverse MR analysis indicated causal effects of AD on glucuronate and ALS on acetylcarnitine (C2). Our study, through genetic means, demonstrates close causal associations between the specific types of CSF metabolites and the risk of NDDS (AD, PD, MS, and ALS), providing useful guidance for future clinical researches.PMID:39641862 | DOI:10.1007/s10048-024-00792-6
New alternative approaches to stroke treatment: the blood cell-derived secretome shows promise in individuals with obesity
Metab Brain Dis. 2024 Dec 6;40(1):56. doi: 10.1007/s11011-024-01491-9.ABSTRACTIschaemic tolerance induced by remote ischaemic conditioning (RIC) has been extensively demonstrated in several preclinical models of cerebral ischaemia. However, animals with common stroke-related comorbidities do not benefit from the recent advances of RIC. Therefore, we investigated two alternative approaches for obese animals with stroke: (1) the efficacy of an additional round of the standard RIC protocol, and (2) the paracrine potential of the blood cell-derived secretome derived from RIC-induced healthy young rats. We found that a second round of remote ischaemic postconditioning (RIPostC) stimulus reduced neurodegeneration and exerted antioxidant effects but failed to decrease the infarct volume and alter glutamate homeostasis. However, when obese rats were administered the secretome from healthy, young RIC-stimulated rats, they exhibited improved neurological post-stroke outcomes. Intravenous administration of the tolerant secretome activated several endogenous mechanisms, including a reduction in the infarct volume and neurodegeneration in the penumbra. Furthermore, the blood cell-derived secretome accelerated brain-to-blood glutamate efflux in obese rats, and demonstrated antioxidant properties that may have contributed to the induction of tolerance in obese rats with stroke. These findings indicate that the blood cell-derived secretome has unique abilities and represents a new potential treatment for individuals with obesity and ischaemic stroke.PMID:39641824 | DOI:10.1007/s11011-024-01491-9
Multi-omics analysis of the molecular mechanisms by which extract of Artemisia selengensis Turcz. ameliorates DBP-induced liver injury
Chem Biodivers. 2024 Dec 6:e202401963. doi: 10.1002/cbdv.202401963. Online ahead of print.ABSTRACTArtemisia selengensis Turcz is a perennial herb belonging to the genus Artemisia in the family Asteraceae. Known for its nutrient richness, distinct flavor, and medicinal properties, Artemisia selengensis Turcz. has garnered attention. However, its efficacy, particularly in alleviating hepatic injury, remains underexplored. This study aims to assess the therapeutic potential of the 50% ethanol extract of Artemisia selengensis Turcz. (ASTE) in a mouse model of Dibutyl phthalate (DBP)-induced liver injury. Through multi-omics analysis, including transcriptomics, metabolomics, and intestinal flora examination, we explored the pathways and key targets of ASTE in treating liver injury. Network pharmacology further identified the crucial components of ASTE for liver injury treatment. Our findings indicate that ASTE affects intestinal flora such as Adlercreutzia through flavonoids, particularly naringin and epicatechin. Additionally, key genes in the PPAR pathway, such as Fabp3, Fabp5, Ehhadh, and Pltp, influence glycerophospholipid metabolism, contributing to liver injury amelioration. This study sheds light on the molecular mechanisms underlying ASTE's hepatoprotective effects, laying the groundwork for its potential application as a functional food.PMID:39641643 | DOI:10.1002/cbdv.202401963
Fructo-oligosaccharides Alleviated Ulcerative Colitis via Gut Microbiota-Dependent Tryptophan Metabolism in Association with Aromatic Hydrocarbon Receptor Activation in Mice
J Agric Food Chem. 2024 Dec 6. doi: 10.1021/acs.jafc.4c07248. Online ahead of print.ABSTRACTFructo-oligosaccharide (FOS) is a typical prebiotic with intestinal health-promoting effects. Here, we explored the anticolitis activity of FOS and clarified the underlying mechanisms. Dextran sulfate sodium (DSS)-induced mice were gavaged with FOS (400 mg/kg) for 37 days, and administration of FOS alleviated DSS-induced colitis symptoms. Besides, FOS improved gut microbiota dysbiosis and modulated the intestinal microbiota-controlled tryptophan metabolic pathways. Targeted metabolomic results showed that FOS significantly increased the colonic levels of indole-3-acetic acid (IAA) and indole-3-propionic acid (IPA) and subsequently increased the expressions of aromatic hydrocarbon receptors (AhR) in the colon and further promoted the expressions of interleukin-22 (IL-22) and intestinal tight junction proteins in the colitis mice. These findings for the first time highlight a novel anticolitis mechanism of FOS by alleviating intestinal microbiota dysbiosis and modulating microbial tryptophan metabolism to promote IAA and IPA production for triggering AhR/IL-22 axis activation.PMID:39641614 | DOI:10.1021/acs.jafc.4c07248
Metabolomics revealed the characteristics of the unique flavor substances of Alxa Allium mongolicum
Food Chem X. 2024 Nov 17;24:101979. doi: 10.1016/j.fochx.2024.101979. eCollection 2024 Dec 30.ABSTRACTAllium mongolicum is a wild vegetable with high nutritional value and is famous for its taste and aroma. This study used headspace solid-phase microextraction-mass spectrometry coupled with gas chromatography-mass spectrometry techniques to study the metabolic profile of A. mongolicum in different ecological environments. A total of 624 volatile organic compounds (VOCs) were identified. Ester compounds, heterocyclic compounds and terpenoids are the key metabolites that determine flavor differences. KEGG analysis showed that monoterpenoid biosynthesis, zein biosynthesis, α-linolenic acid metabolism and secondary metabolite biosynthesis were the most important metabolic pathways. Compared with Minqin A. mongolicum and Tengger A. mongolicum, Alxa A. mongolicum flavor substance notes sensory flavor has more green, fruity, sweet, floral, spicy, metallic, rose, almond, apple, grassy, tropical, citrus, fresh, herbal and other flavor combinations. Overall, this study reveals the main reason for the unique flavor of Alxa A. mongolicum through metabolomic evidence.PMID:39641113 | PMC:PMC11617693 | DOI:10.1016/j.fochx.2024.101979
Metabolomic and transcriptomic analyses jointly reveal the mechanism underlying the reddening of Chimonanthus praecox stamens
Front Plant Sci. 2024 Nov 20;15:1491246. doi: 10.3389/fpls.2024.1491246. eCollection 2024.ABSTRACTINTRODUCTION: Flower characteristics are crucial ornamental and reproductive traits in Chimonanthus praecox. Over its long cultivation history, variations have been observed in the floral organs, primarily in the petals, with limited reports on stamen traits. Stamen variation, integral to the mating system, can enhance the plant's ornamental value and directly impact its reproductive success.METHODS: This study is the first to report the phenomenon of red coloration in C. praecox stamens. Using UPLC-MS/MS, we analyzed the types and quantities of major metabolites in stamens of different colors.RESULTS: Our results indicated that the red coloration was primarily due to the accumulation 42 on of high levels of anthocyanins, specifically cyanidin 3-O-rutinoside and cyanidin 3-O-glucoside. Transcriptomic sequencing identified 63 differentially expressed genes (DEGs) related to the anthocyanin biosynthetic pathway, most showing peak expression during the bud stage. The results of the metabolite analysis and transcriptomic sequencing were similar to those of previous studies on petal reddening, suggesting a close relationship between the mechanisms of stamen and petal reddening.DISCUSSION: This study elucidated the mechanism of stamen reddening in C. praecox, expanding the species' genetic resources and offering insights into color changes across floral tissue..PMID:39640987 | PMC:PMC11618622 | DOI:10.3389/fpls.2024.1491246
Bile molecular landscape provides pathological insight and classifies signatures predictive of carcinoma of the gall bladder
Mol Ther Oncol. 2024 Nov 6;32(4):200904. doi: 10.1016/j.omton.2024.200904. eCollection 2024 Dec 19.ABSTRACTCarcinoma of the gall bladder (CAGB) has a poor prognosis. Molecular analysis of bile could classify indicators of CAGB. Bile samples (n = 87; training cohort) were screened for proteomics and metabolomics signatures of cancer detection. In bile, CAGB showed distinct proteomic (217 upregulated, 258 downregulated) and metabolomic phenotypes (111 upregulated, 505 downregulated, p < 0.05, fold change > 1.5, false discovery rate <0.01) linked to significantly increased inflammation (coagulation, arachidonic acid, bile acid) and alternate energy pathways (pentose-phosphate pathway, amino acids, lipid metabolism); and decreased glycolysis, cholesterol metabolism, PPAR, RAS, and RAP1 signaling, oxidative phosphorylation, and others compared to gallstone or healthy controls (p < 0.05). Bile proteins/metabolites signatures showed significant correlation (r 2 > 0.5, p < 0.05) with clinical parameters. Metabolite/protein signature-based probability of detection for CAGB (cancer) was >90% (p < 0.05), with area under the receiver operating characteristic curve >0.94. Validation of the top four metabolites-toluene, 5,6-DHET, creatine, and phenylacetaldehyde-in separate cohorts (n = 80; bile [T1] and paired plasma [T2]) showed accuracy (99%) and sensitivity/specificity (>98%) for CAGB detection. Tissue validation showed bile 5,6-DHET positively correlated with tissue PCNA (proliferation), and caspase-3 linked to cancer development (r 2 >0.5, p < 0.05). In conclusion, the bile molecular landscape provides critical molecular understanding and outlines metabolomic indicator panels for early CAGB detection.PMID:39640865 | PMC:PMC11617464 | DOI:10.1016/j.omton.2024.200904
Lysophosphatidylcholine induced by fat transplantation regulates hyperalgesia by affecting the dysfunction of ACC perineuronal nets
iScience. 2024 Nov 5;27(12):111274. doi: 10.1016/j.isci.2024.111274. eCollection 2024 Dec 20.ABSTRACTThe pathogenesis of hyperalgesia is complex and can lead to poor clinical treatment. Our study revealed that epididymal white adipose tissue (eWAT) from spared nerve injury (SNI) mice is involved in the occurrence of hyperalgesia after adipose tissue transplantation. We also showed that lysophosphatidylcholine (LPC) is enriched in the eWAT of SNI mice using non-targeted metabolomic analysis and verified that the levels of LPC in plasma and the anterior cingulate cortex (ACC) region increased following eWAT transplantation. Based on the immunohistochemistry results, we observed that LPC in the ACC region activated microglia via the TRPV1/CamkⅡ pathway. Meanwhile, the disruption of perineuronal nets (PNNs) around PV+ neurons in ACC promoted hyperalgesia, and the loss of PNNs and PV+ interneurons might be due to microglial phagocytosis. These findings elucidate the mechanism underlying hyperalgesia from the perspective of lipid metabolite LPC and PNNs and provide potential strategies for the treatment of hyperalgesia.PMID:39640595 | PMC:PMC11617398 | DOI:10.1016/j.isci.2024.111274
Tracking fructose 1,6-bisphosphate dynamics in liver cancer cells using a fluorescent biosensor
iScience. 2024 Nov 6;27(12):111336. doi: 10.1016/j.isci.2024.111336. eCollection 2024 Dec 20.ABSTRACTHYlight is a genetically encoded fluorescent biosensor that ratiometrically monitors fructose 1,6-bisphosphate (FBP), a key glycolytic metabolite. Given the role of glucose in liver cancer metabolism, we expressed HYlight in human liver cancer cells and primary mouse hepatocytes. Through in vitro, in silico, and in cellulo experiments, we showed HYlight's ability to monitor FBP changes linked to glycolysis, not gluconeogenesis. HYlight's affinity for FBP was ∼1 μM and stable within physiological pH range. HYlight demonstrated weak binding to dihydroxyacetone phosphate, and its ratiometric response was influenced by both ionic strength and phosphate. Therefore, simulating cytosolic conditions in vitro was necessary to establish a reliable correlation between HYlight's cellular responses and FBP concentrations. FBP concentrations were found to be in the lower micromolar range, far lower than previous millimolar estimates. Altogether, this biosensor approach offers real-time monitoring of FBP concentrations at single-cell resolution, making it an invaluable tool for the understanding of cancer metabolism.PMID:39640569 | PMC:PMC11617404 | DOI:10.1016/j.isci.2024.111336