PubMed

Radiat Res. 2024 Nov 7. doi: 10.1667/RADE-23-00261.1. Online ahead of print.ABSTRACTNational security concerns regarding radiological incidents, accidental or intentional in nature, have increased substantially over the past few years. A primary area of intense planning is the assessment of exposed individuals and timely medical management. However, exposed individuals who receive survivable radiation doses may develop delayed effects of acute radiation exposure many months or years later. Therefore, it is necessary to identify such individuals and determine whether their symptoms may have been initiated by radiation and require complex medical interventions. We previously developed early response metabolomic biosignatures in biofluids from non-human primates exposed to a total body gamma radiation dose of 4 Gy (up to 60 days). A follow-up of these animals has been ongoing with samples consistently collected every few months for up to 2 years after exposure, providing a unique cohort to determine if a radiation signal persists longer than 2 months. Metabolic fingerprinting in urine and serum determined that exposed animals remain metabolically different from pre-exposure levels and from age-matched controls, and the pre-determined biosignature maintains high sensitivity and specificity. Significant perturbations in tricarboxylic acid intermediates, cofactors and nucleotide metabolism were noted, signifying energetic changes that could be attributed to or perpetuate altered mitochondrial dynamics. Importantly, these animals have begun developing diseases such as hypertension much earlier than their age-matched controls, further emphasizing that radiation exposure may lead to accelerated aging. This NHP cohort provides important information and highlights the potential of metabolomics in determining persistent changes and a radiation-specific signature that can be correlated to phenotype.PMID:39504997 | DOI:10.1667/RADE-23-00261.1

Cell Metab. 2024 Nov 2:S1550-4131(24)00399-1. doi: 10.1016/j.cmet.2024.10.003. Online ahead of print.ABSTRACTStress and circadian systems are interconnected through the hypothalamic-pituitary-adrenal (HPA) axis to maintain responses to external stimuli. Yet, the mechanisms of how such signals are orchestrated remain unknown. Here, we uncover the gut microbiota as a regulator of HPA-axis rhythmicity. Microbial depletion disturbs the brain transcriptome and metabolome in stress-responding pathways in the hippocampus and amygdala across the day. This is coupled with a dysregulation of the circadian pacemaker in the brain that results in perturbed glucocorticoid rhythmicity. The resulting hyper-activation of the HPA axis at the sleep/wake transition drives time-of-day-specific impairments of the stress response and stress-sensitive behaviors. Finally, microbiota transplantation confirmed that diurnal oscillations of gut microbes underlie altered glucocorticoid secretion and that L. reuteri is a candidate strain for such effects. Our data offer compelling evidence that the microbiota regulates stress responsiveness in a circadian manner and is necessary to respond adaptively to stressors throughout the day.PMID:39504963 | DOI:10.1016/j.cmet.2024.10.003

Food Chem. 2024 Oct 28;464(Pt 3):141786. doi: 10.1016/j.foodchem.2024.141786. Online ahead of print.ABSTRACTFermentation of red grapefruit by Monascus purpureus (M. purpureus) results in complex changes in flavor compounds and metabolic profiles, but the specifics of these alterations are not well understood. This study aimed to investigate the changes in flavor compounds and metabolomic traits during this fermentation process. Using Headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) with non-targeted metabolomics, we analyzed flavor compounds and measured physicochemical indices throughout the fermentation period. We identified 23 volatile flavor metabolites before and after fermentation, focusing on acids, alcohols, and aldehydes, of these, 9 showed an upward effect and 14 showed a downward effect. Key metabolic pathways involved included butyric acid, taurine, and hypotaurine, with notable downregulation of acetone and 1-butanol in the butyric acid pathway. The study reveals that butyric acid-related metabolism influences other pathways such as glycolysis, fatty acid metabolism, and the tricarboxylic acid cycle in M. purpureus. These findings provide insights into the generation of flavor compounds during fermentation and offer a theoretical basis for the industrial production of fermented citrus fruits.PMID:39504903 | DOI:10.1016/j.foodchem.2024.141786

J Pharm Biomed Anal. 2024 Oct 24;253:116520. doi: 10.1016/j.jpba.2024.116520. Online ahead of print.ABSTRACTWithania somnifera L. (Solanaceae), for over 3000 years, has been considered an essential herb in Ayurvedic medicine. The roots of W. somnifera contain metabolites mainly belonging to steroidal lactones called withanolides, which possess various pharmacological activities such as neuroprotective, cardioprotective, anti-diabetic, antioxidant and anti-inflammatory. Since the demand on the market for W. somnifera extracts is increasing, with the aim to find an ecological and environmentally friendly strategy of extraction, the roots were submitted to different extraction techniques (macerations, ultrasound-assisted extraction and solid-liquid dynamic extraction) using EtOH:H2O 50:50, 75:25, 100:0. W. somnifera extracts were investigated by an integrated LC-ESI/QExactive/MS/MS and NMR approach to obtain comprehensive metabolite profiles. Principal Component Analysis of LC-MS and NMR data revealed how the extraction method and the solvent can affect the chemical profile of the extracts. Extracts obtained by maceration exhibited the highest amount of withanolides and withanosides, while the SLDE-Naviglio EtOH extract showed the highest amount of metabolites as benzoic acid, tropane alkaloids and sarcosine, reported for their CNS activity. Moreover, based on the use of this plant in the treatment of neurological disorders, the tyrosinase inhibitory activity of all the extracts was herein tested by spectrophotometric assay, showing IC50 values in a range of 32.86-85.36 µg/ml.PMID:39504741 | DOI:10.1016/j.jpba.2024.116520

J Chromatogr A. 2024 Oct 28;1738:465480. doi: 10.1016/j.chroma.2024.465480. Online ahead of print.ABSTRACTAmino compounds are of significant interest in dietary, clinical, and quality control fields. Efficient extraction is crucial for comprehensive metabolomics, especially for amino acids and biogenic amines, but traditional solid-phase extraction (SPE) methods are costly and require large solvent volumes. Miniaturized SPE techniques, like pipette-tip micro-solid-phase extraction (PT-µ-SPE), offer promising alternatives by improving throughput and reducing solvent and sorbent usage. This study presents PT-µ-SPE for the screening and quantification of amino compounds in bee products, particularly honey. The method involves derivatization with diethyl ethoxymethylenemalonate (DEEMM) and analysis using liquid chromatography-triple quadrupole mass spectrometry. Silica-based SCX sorbents were effective for a broad range of amino compounds, while WCX sorbents were better for aliphatic amines. The method's extraction efficiency was assessed across sample loading, washing, and elution solution, with recovery rates of 70 - 120% in oat bran, sea buckthorn leaves, and honey extracts. Matrix effects were observed for four amino compounds in honey. Limits of detection (LoD) and quantification (LoQ) ranged from 0.37 to 57 µg L⁻¹ and 1.13 to 174 µg L⁻¹, respectively. Covering 48 amino compounds under different PT-µ-SPE conditions, this method has been applied to several samples, demonstrating accuracy, environmental sustainability, cost-effectiveness, portability, and versatility in amino compound analysis.PMID:39504703 | DOI:10.1016/j.chroma.2024.465480

Plant Physiol Biochem. 2024 Nov 2;217:109265. doi: 10.1016/j.plaphy.2024.109265. Online ahead of print.ABSTRACTAs a major food crop, maize (Zea mays L.) is facing a serious threat of lead (Pb) pollution. Research into its Pb tolerance is crucial for ensuring food security and human health, however, the molecular mechanism underlying the response to Pb remains incompletely understood. Here, we investigated the transcriptomic and metabolome of two maize lines (BY001, a Pb-resistant line; BY006, a Pb-sensitive line) under different concentrations of Pb stress (0, 500, 1000, 2000 and 3000 mg/L). The results showed that BY001 performed well, whereas the BY006 exhibited minimal development of lateral roots upon exposure to high concentration of Pb. The antioxidant enzyme activity of BY001 remained relatively stable, while that of BY006 declined significantly. Transcriptomic analysis revealed that under high concentration of Pb stress, BY001 produced 5057 differentially expressed genes, whereas BY006 produced 3374. Functional annotation showed that these genes were primarily involved in carbohydrate metabolism, root growth, and plant resistance to external Pb stress. Further untargeted metabolomics indicated that Pb stress triggered distinct alterations in the levels of 47 diverse metabolite types across 13 distinct classes, particularly amino acids, carbohydrates, and organic acids. A conjoint omics analysis suggested that the pathways of starch and sucrose metabolism, as well as cutin, suberin, and wax biosynthesis in BY001, play a key role in the Pb resistance. These findings elucidate the biological mechanisms employed by maize to counter the effects of Pb stress, and provide a basis for breeding of maize cultivars with low Pb accumulation or tolerance.PMID:39504657 | DOI:10.1016/j.plaphy.2024.109265

Plant Physiol Biochem. 2024 Nov 4;217:109269. doi: 10.1016/j.plaphy.2024.109269. Online ahead of print.ABSTRACTHibiscus mutabilis, commonly known as the cotton rose, is a widely cultivated ornamental and has been acclaimed as the representative flower of the 2024 World Horticultural Exposition. The growth and ornamental characteristics of Hibiscus mutabilis can be affected by drought stress. Therefore, we investigated the physiological and metabolic responses of drought-sensitive Hibiscus mutabilis JRX-1 and drought-tolerant Hibiscus mutabilis CDS-4 under drought stress. The results of the physiological analyses revealed that, compared to JRX-1,CDS-4 maintained good growth and greater water use efficiency through stronger antioxidant defences, osmoregulatory capacity and stomatal regulation. A total of 3277 metabolites were identified in positive and negative ion modes, of which 663 metabolites presented changes in expression under drought conditions, including 306 upregulated metabolites and 357 downregulated metabolites. Secondary metabolites, such as flavonoids and diterpenoids, are crucial in the plant response to drought stress. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the differentially aboundant metabolites were significantly enriched in the pathways valine, leucine and isoleucine degradation; linoleic acid metabolism; one carbon pool by folate; and folate biosynthesis. The results of this study will not only help to elucidate and apply the physiological and metabolic regulatory strategies of Hibiscus mutabilis to improve its adaptation to water deficit conditions, but will also provide valuable guidance to breeders and molecular biologists in the screening and use of drought resistant genes in ornamental plants.PMID:39504656 | DOI:10.1016/j.plaphy.2024.109269

Sci Transl Med. 2024 Nov 6;16(772):eadh9940. doi: 10.1126/scitranslmed.adh9940. Epub 2024 Nov 6.ABSTRACTNonalcoholic fatty liver disease (NAFLD) has become a common health care burden worldwide. The high heterogeneity of NAFLD remains elusive and impairs outcomes of clinical diagnosis and pharmacotherapy. Several NAFLD classifications have been proposed on the basis of clinical, genetic, alcoholic, or serum metabolic analyses. Yet, accurately predicting the progression of NAFLD to cirrhosis or hepatocellular carcinoma (HCC) in patients remains a challenge. Here, on the basis of a Chinese cohort of patients, we classified NAFLD into three distinct molecular subtypes (NAFLD-mSI, NAFLD-mSII, and NAFLD-mSIII) using integrative multiomics including whole-genome sequencing (WGS), proteomics, phosphoproteomics, lipidomics, and metabolomics across a broad range of liver, blood, and urine specimens. We found that NAFLD-mSI had higher expression of CYP1A2 and CYP3A4, which alleviate hepatic steatosis through mediating free fatty acid/bile acid-mTOR-FXR/PPARα signaling. NAFLD-mSII displayed an elevated risk of liver cirrhosis along with increased hepatic infiltration of M1 and M2 macrophages because of lipid-triggered hepatic CCL2 and CRP production. NAFLD-mSIII exhibited a potential risk for HCC development by increased transcription of CEBPB- and ERCC3-regulated oncogenes because of activation of the EGF-EGFR/CHKA/PI3K-PDK1-AKT cascade. Next, we validated the existence of these three NAFLD molecular subtypes in an external cohort comprising 92 patients with NAFLD across three different Chinese hospitals. These findings may aid in understanding the molecular features underlying NAFLD heterogeneity, thereby facilitating clinical diagnosis and treatment strategies with the aim of preventing the development of liver cirrhosis and HCC.PMID:39504356 | DOI:10.1126/scitranslmed.adh9940

Anal Chem. 2024 Nov 6. doi: 10.1021/acs.analchem.4c03553. Online ahead of print.ABSTRACTSpatial metabolomics has emerged as a powerful tool capable of revealing metabolic gradients throughout complex heterogeneous tissues. While mass spectrometry imaging (MSI) technologies designed to generate spatial metabolomic data have improved significantly over time, metabolite coverage is still a significant limitation. It is possible to achieve deeper metabolite coverage by imaging in positive and negative polarities or imaging several serial sections with different targeted biomolecular classes. However, this significantly increases the number of tissue samples required for biological studies and reduces the capacity for larger sample cohorts. Herein, we introduce lithium-doped nanospray desorption electrospray ionization (nano-DESI) as a simple and robust method to increase spatial metabolomics coverage, which is achieved through enhancements to ionization efficiencies in positive ion mode for metabolites and lipids lacking basic moieties, and improved structurally diagnostic tandem mass spectra for [M + Li]+ adducts. Specifically, signal intensities were found to be enhanced by 10-1000× for 96 compounds including small molecule metabolites, fatty acids, neutral lipids (e.g., diacylglycerols, DAG), and phospholipids when lithium was added to the ESI solvent. In addition, proof-of-principle results reveal that lithium-doped nano-DESI MSI was able to comprehensively visualize metabolites and lipids in the prostaglandin (PG) biosynthetic pathway with PG isomeric resolution in an ovarian tumor section. These data show colocalization of fatty acid (FA) 20:4 containing DAGs, FA 20:4 monoacylglycerols (MAGs), and FA 20:4 with PGE2 and disparate localizations of PGD2. Overall, this study describes a simple and powerful approach to more comprehensively probe the spatial metabolome with MSI.PMID:39504343 | DOI:10.1021/acs.analchem.4c03553

Cell Rep. 2024 Nov 5;43(11):114913. doi: 10.1016/j.celrep.2024.114913. Online ahead of print.ABSTRACTMetabolites that mark aging are not fully known. We analyze 408 plasma metabolites in Long Life Family Study participants to characterize markers of age, aging, extreme longevity, and mortality. We identify 308 metabolites associated with age, 258 metabolites that change over time, 230 metabolites associated with extreme longevity, and 152 metabolites associated with mortality risk. We replicate many associations in independent studies. By summarizing the results into 19 signatures, we differentiate between metabolites that may mark aging-associated compensatory mechanisms from metabolites that mark cumulative damage of aging and from metabolites that characterize extreme longevity. We generate and validate a metabolomic clock that predicts biological age. Network analysis of the age-associated metabolites reveals a critical role of essential fatty acids to connect lipids with other metabolic processes. These results characterize many metabolites involved in aging and point to nutrition as a source of intervention for healthy aging therapeutics.PMID:39504246 | DOI:10.1016/j.celrep.2024.114913

Arch Gynecol Obstet. 2024 Nov 6. doi: 10.1007/s00404-024-07695-9. Online ahead of print.ABSTRACTPURPOSE: To explore the effects of high-altitude hypoxia on the microenvironment of oocyte development and fertilization potential, we compared the metabolomic patterns of follicular fluid from women living in different altitude areas and traced their oocyte maturation and subsequent development.METHODS: A total of 315 clinical cases were collected and divided into three groups according to their residence altitudes: 138 cases in low-altitude (< 2300 m) group, 100 cases in middle-altitude (2300-2800 m) group and 77 cases in high-altitude (> 2800 m) group. The clinical outcomes were statistically estimated, including hormonal level, oocyte maturation, in vitro fertilization, and embryo development. Meanwhile, a metabolomic analysis was performed on the follicular fluid of women from different groups using ultra-high-performance liquid chromatography and high-resolution mass spectrometry and differential metabolites were analyzed through the KEGG pathway.RESULTS: The clinical data indicated that the physical condition and reproductive hormone secretion were similar among different groups. Although personalized gonadotropin-releasing hormone strategies were applied, the numbers of antral follicles and obtained oocytes were not impacted by the residence altitude change. In in vitro culture, the maturing rate, fertility rate and cleavage rate of high-altitude group were compared with the other groups. However, the rates of high-quality embryo, formative blastocyst, and available blastocyst were gradually decreased with the rise of residence altitude. Metabolome analysis identified 1193 metabolites in female follicular fluid. Differential analysis indicated that metabolic components in follicular fluid were remarkably changed with the elevation of residence altitude. These differential metabolites were closely related with amino acid metabolism, protein digestion and absorption, oocyte meiosis and steroid biosynthesis.CONCLUSION: The residence altitude alters the microenvironment of follicular fluid, which could damage the oocyte developmental potential. This study provides diagnostic basis and therapeutic targets for research on female oocyte and embryo development.PMID:39503772 | DOI:10.1007/s00404-024-07695-9

J Sep Sci. 2024 Nov;47(21):e70019. doi: 10.1002/jssc.70019.ABSTRACTGuyinjian (GYJ) is a classic traditional Chinese medicine formula for the treatment of polycystic ovary syndrome, ovulation disorders, immuno-sterility, oligomenorrhea with kidney deficiency, and so forth. Due to the unclear chemical components of GYJ, the elucidation of the pharmacological mechanism, and the comprehensive development and utilization of GYJ in clinical is being restricted. In this study, ultra-high-performance liquid chromatography with quadrupole time-of-flight-tandem mass spectrometry combined with the Progenesis QI platform and using reference standards, online and self-built databases matching, fragmentation rules analysis of mass spectrometry peaks, a total of 235 compounds were preliminarily characterized, including 69 flavonoids, 65 terpenoids, 34 phenylpropanoids, 22 saccharides, sugar esters, and glycosides, 15 organic acids, and 30 others. These compounds may reflect the chemical properties of GYJ. The method established in this study can systematically, rapidly, and accurately resolve the chemical components in GYJ, which lays the foundation for further establishment of the pharmacodynamic substance basis and quality control.PMID:39503440 | DOI:10.1002/jssc.70019

Mult Scler. 2024 Nov 6:13524585241292974. doi: 10.1177/13524585241292974. Online ahead of print.ABSTRACTThe pathophysiology of multiple sclerosis (MS) remains poorly understood despite decades of tremendous research efforts. Advances in neuroradiography coupled with availability of unbiased approaches including spatial transcriptomics, proteomics, metabolomics, and lipidomics that are compatible with brain and fluid specimens from patients raise hope that discovery of novel disease drivers is on the horizon. Once thought to be little more than salty bathwater, our modern understanding of cerebrospinal fluid (CSF) suggests the CSF as a compelling, critical regulator of brain function in health and disease. Recent studies in the field have reinvigorated interest in CSF as a medium to better understand MS and to deliver disease-modifying therapies. In turn, the choroid plexus, an epithelial tissue located within each brain ventricle that regulates CSF and forms a key blood-CSF barrier, is uniquely positioned to orchestrate neuroinflammation associated with MS. In this perspective review, we will discuss what is known about the choroid plexus as a conductor of immune responses and how it may propagate neuroinflammation associated with MS via the CSF.PMID:39503321 | DOI:10.1177/13524585241292974

Plant Cell Environ. 2024 Nov 6. doi: 10.1111/pce.15269. Online ahead of print.ABSTRACTAn autofluorescent inclusion (AFI) specifically accumulated in mesophyll cells (MCs) of non-salt-secretor mangrove was found to be related to salt, but its biosynthesis and spatial distribution characteristics remain unclear. Here, Kandelia obovata served as the experimental material, and the composition of AFI was identified as condensed tannin (CT). Na contents increased in purified AFIs under NaCl treatment, while Na+ efflux in MCs was lower than the control. In vitro, Na+ addition caused aggregations of AFIs. Proteins related to Na+/H+ and vesicle transport were identified in the purified AFIs by liquid chromatography-mass spectrometry. TEM images revealed the structures involved in CT biosynthesis in chloroplasts and CT accretions in vacuoles were more visible under higher salinity. Spatial metabolomics analysis on flavonoid metabolites involving in CT biosynthesis illustrated those flavonoids and three CT monomers were positively related to salt in MCs. Real-time quantitative PCR verified the genes encoding enzymes for CT biosynthesis were upregulated accordingly. Taken together, CT biosynthesis is positively correlated with Na accumulation in leaves. The CTs synthesized in chloroplasts are transported as shuttles to vacuole via cytoplasm, facilitating the sequestration and compartmentalization of excessive Na+ ions into the vacuole, which confers non-salt-secretor mangrove K. obovata a higher salt tolerance.PMID:39503313 | DOI:10.1111/pce.15269

Pediatr Allergy Immunol. 2024 Nov;35(11):e14274. doi: 10.1111/pai.14274.ABSTRACTBACKGROUND: Infants hospitalized for bronchiolitis are at high risk for developing recurrent wheeze in childhood. The role of airway lipids in the link between these two conditions remains unclear. This study aimed to identify the association between airway lipids in infants hospitalized for bronchiolitis and the development of recurrent wheeze, with a focus on immunoglobulin E (IgE) sensitization.METHODS: In a multicenter prospective cohort study of 919 infants (age <1 year) hospitalized for bronchiolitis, we performed lipidomic profiling of nasopharyngeal airway specimens collected at hospitalization. We first identified lipid modules composed of highly correlated lipids by performing weighted correlation network analysis. We then examined the longitudinal association of those lipid modules with the rate of recurrent wheeze by age 3 years after discharge from hospitalization for bronchiolitis. We also examined the associations of lipid modules with IgE non-sensitized (i.e., neither sensitized at admission nor at age 3 years) and IgE-sensitized (i.e., sensitized at admission and/or at age 3 years) recurrent wheeze by age 3 years, respectively.RESULTS: Our analysis identified 15 distinct lipid modules in the nasopharyngeal airway lipidome data. Overall, lipid modules composed of triacylglycerols (hazard ratio [HR] 1.78, 95% confidence interval [CI] 1.26-2.51, FDR < 0.01) and sphingolipids (HR 1.74, 95% CI 1.25-2.44, FDR <0.01) had the strongest associations with recurrent wheeze development. Stratification by IgE sensitization revealed differential associations. For example, the module composed of triacylglycerols was significantly associated with IgE non-sensitized recurrent wheeze, whereas the module composed of sphingolipids was significantly associated with IgE-sensitized recurrent wheeze (both FDR <0.05).CONCLUSION: Distinct nasopharyngeal airway lipid modules are associated with recurrent wheeze development following severe bronchiolitis, with different patterns based on IgE sensitization status.PMID:39503262 | DOI:10.1111/pai.14274

Food Chem. 2024 Oct 18;464(Pt 2):141683. doi: 10.1016/j.foodchem.2024.141683. Online ahead of print.ABSTRACTCoffee is a widely popular beverage worldwide, known for its distinct sensory properties which are greatly affected by geographical origin. Herein, we performed an untargeted metabolomic evaluation of green coffee beans (n = 40) from four different regions in Brazil: Cerrado Mineiro, Sul de Minas, Caparaó, and Mogiana Paulista; by using UHPLC-HRMS (ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry). The most significant metabolites responsible for coffee characterization were theobromine, zeatin, phenylacetaldehyde, 2-acetyl-1-pyrroline, chlorogenic acids, ferulic acid, p-coumaric acid, abscisic acid, and jasmonic acid. Our findings demonstrate that the green coffee cultivated in Cerrado Mineiro, the most valuable among the four samples evaluated, exhibits a unique and typical metabolite profile, setting it apart from the coffee beans grown in other regions. Finally, the findings reported may be relevant for coffee producers in the Cerrado Mineiro area, as they contribute to establishing a certificate of origin for their high-quality product.PMID:39503088 | DOI:10.1016/j.foodchem.2024.141683

Transl Gastroenterol Hepatol. 2024 Aug 9;9:65. doi: 10.21037/tgh-24-14. eCollection 2024.ABSTRACTBACKGROUND: Acute pancreatitis (AP) is a complex inflammatory condition with rising incidence globally. Despite various known causes, early diagnosis remains challenging due to limitations in existing biomarkers. Metabolomics offers a promising avenue for identifying novel biomarkers and elucidating underlying pathophysiological mechanisms. Previous AP metabolomics studies primarily focused on analyzing serum, urine, and pancreatic tissues from patients or animal models. However, systematic metabolomics studies that analyze multiple tissues simultaneously are still lacking. The primary aim of our study is to obtain valuable clues to explore the pathophysiological mechanisms of AP and discover novel biomarkers to enable early detection.METHODS: Using a mouse model of AP induced by cerulein, we conducted gas chromatography-mass spectrometry (GC-MS) metabolomic analysis on serum, pancreas, liver, spleen, colon, and kidney samples. Twelve male C57BL/6J mice were randomly divided into AP and control (CON) groups. Serum and tissue samples were collected, processed, and analyzed using established protocols. Multivariate statistical analysis was employed to identify differential metabolites and impacted metabolic pathways.RESULTS: Distinct metabolic profiles were observed between AP and CON groups across multiple tissues. Elevated levels of ketone bodies, amino acids, citric acid, and lipids were noted, with significant differences in metabolite levels identified. Notably, 3-hydroxybutyric acid (3-HBA), branched-chain amino acids (BCAAs), phenylalanine, and L-lysine showed consistent alterations, suggesting their potential as early diagnostic biomarkers for AP. Pathway analysis revealed perturbations in several metabolic pathways, providing insights into the pathophysiological mechanisms underlying AP.CONCLUSIONS: Our study highlights the utility of metabolomics in identifying potential biomarkers for early diagnosis of AP and elucidating associated metabolic pathways. 3-HBA, BCAAs, phenylalanine and L-lysine emerge as promising biomarkers for further clinical validation. These findings contribute to a better understanding of AP pathophysiology and underscore the potential of metabolomics in precision medicine approaches for AP management.PMID:39503020 | PMC:PMC11535808 | DOI:10.21037/tgh-24-14

Front Nutr. 2024 Oct 22;11:1438740. doi: 10.3389/fnut.2024.1438740. eCollection 2024.ABSTRACTConsumption of plant-based diets, including vegan diets, necessitates attention to the quality of the diet for the prevention and early detection of nutritional deficiencies. Within the VEGANScreener project, a unique brief screening tool for the assessment and monitoring of diet quality among vegans in Europe was developed. To provide a standardized tool for public use, a clinical study will be conducted to evaluate the VEGANScreener against a reference dietary assessment method and nutritional biomarkers. An observational study is set to include 600 participants across five European sites - Belgium, Czech Republic, Germany, Spain, and Switzerland. In total, 400 self-reported vegans (≥2 years on a vegan diet), and 170 self-reported omnivore controls will be examined, aged between 18 and 65 years, with males and females being equally represented in a 1:1 ratio for two age groups (18-35 and 36-65 years). Participants with diseases affecting metabolism and intestinal integrity will be excluded. The clinical assessment will include a structured medical history, along with taking blood pressure and anthropometric measurements. Blood and urine will be sampled and analyzed for a set of dietary biomarkers. Metabolomic analyses will be conducted to explore potential novel biomarkers of vegan diet. Moreover, saliva samples will be collected to assess the metabolome and the microbiome. Participants will receive instructions to complete a nonconsecutive 4-day diet record, along with the VEGANScreener, a socio-demographic survey, a well-being survey, and a FFQ. To evaluate reproducibility, the VEGANScreener will be administered twice over a three-weeks period. Among vegans, the construct validity and criterion validity of the VEGANScreener will be analyzed through associations of the score with nutrient and food group intakes, diet quality scores assessed from the 4-day diet records, and associations with the dietary biomarkers. Secondary outcomes will include analysis of dietary data, metabolomics, and microbiomes in all participants. Major nutrient sources and variations will be assessed in the sample. Exploratory metabolomic analysis will be performed using multivariable statistics and regression analysis to identify novel biomarkers. Standard statistical models will be implemented for cross-sectional comparisons of geographical groups and vegans versus omnivores.PMID:39502879 | PMC:PMC11534613 | DOI:10.3389/fnut.2024.1438740

Med Pharm Rep. 2024 Oct;97(4):467-476. doi: 10.15386/mpr-2780. Epub 2024 Oct 30.ABSTRACTBACKGROUND AND AIM: Tacrolimus (TAC) has significantly improved kidney graft survival following transplantation, though it is associated with adverse side effects. The most prevalent complication resulting from excessive TAC exposure is the onset of de novo diabetes mellitus (DM), a condition that can negatively impact both renal graft function and patient outcomes. De novo DM is linked to an increased risk of chronic transplant dysfunction, as well as cardiovascular morbidity and mortality. Although the underlying mechanisms remain unclear, emerging research in the field of omics shows promise. The aim of this study was to investigate the metabolomic profile of kidney transplant patients who developed de novo DM, in comparison to those who did not, following TAC exposure, using untargeted metabolomic analysis through ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) and machine learning algorithms.METHODS: A cohort of 34 kidney transplant patients on a Tacrolimus regimen for at least 6 months was enrolled in the study, with serum samples collected from each patient. Comprehensive profiling of serum metabolites was performed, enabling the classification of patients into de novo diabetes mellitus and non diabetes groups. The metabolomic analysis of serum was conducted using UHPLC-MS.RESULTS: Of the 34 patients, 16 were diagnosed with TAC-induced diabetes. A total of 334 metabolites were identified in the serum samples, of which 10 demonstrated a significant correlation with the de novo diabetes mellitus group. Most of these metabolites were linked to alterations in lipid metabolism.CONCLUSION: The application of metabolomics in kidney transplant patients undergoing a Tacrolimus regimen is both feasible and effective in identifying metabolites associated with de novo diabetes mellitus. This approach may provide valuable insights into the metabolic alterations underlying TAC-induced diabetes.PMID:39502769 | PMC:PMC11534379 | DOI:10.15386/mpr-2780

Int J Microbiol. 2024 Oct 28;2024:1763495. doi: 10.1155/2024/1763495. eCollection 2024.ABSTRACTToxigenic fungi are capable of producing toxic metabolites, called mycotoxins. But the presence of silent and lowly expressed genes represents the main challenge for the discovery of novel mycotoxins, especially their lesser-known forms, commonly referred to as "emerging mycotoxins." Epigenetic modifiers (EMs) are compounds that are able to alter the production of metabolites through the induction of silent biosynthetic pathways leading to an enhanced chemical diversity. The aim of this study was to assess the effects of different chemical modulators on the metabolic profiles of the well-known toxigenic fungal species, Fusarium verticillioides. Four EMs, 5-azacytidine, sodium butyrate, nicotinamide (NIC), and sodium valproate (SV), were used. Following their addition to Fusarium verticillioides cultures, the metabolic profiles were analyzed by using UHPLC-HRMS/MS under targeted and untargeted metabolomics approaches. Metabolites were putatively annotated through the use of MS-DIAL and MS-FINDER. Our results show that the treatment with SV induced the most important alteration of the secondary metabolic profile of F. verticillioides, by promoting the expression of cryptic genes. Among the 50 most discriminating metabolites across five culture conditions, 12 were fusarins or fusarin analogs. In contrast, SB and NIC had little impact on these metabolites. The study highlights SV's ability to alter gene expression by inhibiting DNA deacetylation in fungal strains. This research could have significant implications for agriculture and food industry, especially in regions facing major mycotoxin challenges.PMID:39502514 | PMC:PMC11535422 | DOI:10.1155/2024/1763495