PubMed

Sci Rep. 2024 Nov 6;14(1):27010. doi: 10.1038/s41598-024-75773-8.ABSTRACTSpices played crucial and variable roles in traditions, culture, history, religious ceremonials and festivals along with fetching food flavor and microbial protection globally due to presence of structurally unique and multi-natured chemotypes. Their existence in dishes portrayed key roles in improving shelf life by regulating spoilage of cuisine with different synergistic mechanism. Histo-anatomically (A) sowa exhibited distinguished cellular attributes which created remarkable differences with T. ammi. HPTLC chemometrics of both fruits revealed several peaks for active metabolomics with unique isocratic combination of menstruum. GC-MS study of hydro-distillate exhibited presence of monoterpenic cyclic and aromatic hydrocarbons, alcoholic and ketonic groups along with phenolic derivative that covers majorly 90% of total metabolites. Combined essential oils (EOs 1 + 2) of both fruits showed excellent antimicrobial activity against various clinical pathogenic strains such as K. pneumoniae at 10 µL/mL, S. aureus at 2.5 µL/mL, E. coli and E. faecalis at 1.25 µL/mL, and MRSA and Bcereus at 0.625 µL/mL and (C) albicans at 0.312 µL/mL as the MIC. The antioxidant study of (EOs 1 + 2) with maximum inhibition percentage to DPPH assay was 84.02 ± 1.05 at 100 µg/mL, and minimal inhibition was 72.31 ± 0.63 at 5 µg/mL with IC50 value 4.69 ± 0.22 µg/mL, while ABTS assay extreme was 79.15 ± 2.14 µg/mL and minimal was 67 ± 1.34 with the IC50 value of 18.37 ± 0.15 µg/mL, in superoxide assay uppermost inhibition was 81.03 ± 0.27 µg/mL and lowest was at 65.16 ± 3.15 with the IC50 value 16.46 ± 0.54, and H2O2 radical scavenging activity, predominant value was 78.01 ± 0.47 and least was 64.1 ± 2.01 with IC50 15.58 ± 0.34. These comparative key diagnostic features and synergistic effect of multicomponent natural antimicrobials will provide profound intellect of ancient utility and further scientists to explore their multiple mechanistic modality and application in food and beverages industry.PMID:39505931 | DOI:10.1038/s41598-024-75773-8

Sci Rep. 2024 Nov 6;14(1):26875. doi: 10.1038/s41598-024-75300-9.ABSTRACTThe cation-independent mannose 6-phosphate receptor (CI-MPR) is clinically significant in the treatment of patients with lysosomal storage diseases because it functions in the biogenesis of lysosomes by transporting mannose 6-phosphate (M6P)-containing lysosomal enzymes to endosomal compartments. CI-MPR is multifunctional and modulates embryonic growth and fetal size by downregulating circulating levels of the peptide hormone insulin-like growth factor 2 (IGF2). The extracellular region of CI-MPR comprises 15 homologous domains with binding sites for M6P-containing ligands located in domains 3, 5, 9, and 15, whereas IGF2 interacts with residues in domain 11. How a particular ligand affects the receptor's conformation or its ability to bind other ligands remains poorly understood. To address these questions, we purified a soluble form of the receptor from newborn calf serum, carried out glycoproteomics to define the N-glycans at its 19 potential glycosylation sites, probed its ability to bind lysosomal enzymes in the presence and absence of IGF2 using surface plasmon resonance, and assessed its conformation in the presence and absence of IGF2 by negative-staining electron microscopy and hydroxyl radical protein footprinting studies. Together, our findings support the hypothesis that IGF2 acts as an allosteric inhibitor of lysosomal enzyme binding by inducing global conformational changes of CI-MPR.PMID:39505925 | DOI:10.1038/s41598-024-75300-9

Neuroimage. 2024 Nov 4:120918. doi: 10.1016/j.neuroimage.2024.120918. Online ahead of print.ABSTRACTBACKGROUND: Prior efforts have revealed changes in gut microbiome, circulating metabolome, and multimodal neuroimaging features in cerebral small vessel disease (CSVD). However, there is a paucity of research integrating the multi-omic information to characterize the role of the microbiota-gut-brain axis in CSVD.METHODS: We collected gut microbiome, fecal and blood metabolome, multimodal magnetic resonance imaging data from 37 CSVD patients with white matter hyperintensities and 46 healthy controls. Between-group comparison was performed to identify the differential gut microbial taxa, followed by performance of multi-stage microbiome-metabolome-neuroimaging-neuropsychology correlation analyses in CSVD patients.RESULTS: Our data showed both depleted and enriched gut microbes in CSVD patients. Among the differential microbes, Haemophilus and Akkermansia were associated with a range of metabolites enriched for Aminoacyl-tRNA biosynthesis pathway. Furthermore, the affected metabolites were associated with neuroimaging measures involving gray matter morphology, spontaneous intrinsic brain activity, white matter integrity, and global structural network topology, which were in turn related to cognition and emotion in CSVD patients.CONCLUSION: Our findings provide an integrative framework to understand the pathophysiological mechanisms underlying the interplay between gut microbiota dysbiosis and CSVD, highlighting the potential of targeting the microbiota-gut-brain axis as a therapeutic strategy in CSVD patients.PMID:39505226 | DOI:10.1016/j.neuroimage.2024.120918

Mol Metab. 2024 Nov 4:102052. doi: 10.1016/j.molmet.2024.102052. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Deficiency in the transcription factor (TF) GLI-Similar 3 (GLIS3) in humans and mice leads to the development of polycystic kidney disease (PKD). In this study, we investigate the role of GLIS3 in the regulation of energy metabolism and mitochondrial functions in relation to its role in normal kidney and metabolic reprogramming in PKD pathogenesis.APPROACH AND RESULTS: Transcriptomics, cistromics, and metabolomics were used to obtain insights into the role of GLIS3 in the regulation of energy homeostasis and mitochondrial metabolism in normal kidney and PKD pathogenesis using GLIS3-deficient mice. Transcriptome analysis showed that many genes critical for mitochondrial biogenesis, oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and the tricarboxylic acid (TCA) cycle, including Tfam, Tfb1m, Tfb2m, Ppargc1a, Ppargc1b, Atp5j2, Hadha, and Sdha, are significantly suppressed in kidneys from both ubiquitous and tissue-specific Glis3-deficient mice. ChIP-Seq analysis demonstrated that GLIS3 is associated with the regulatory region of many of these genes, indicating that their transcription is directly regulated by GLIS3. Cistrome analyses revealed that GLIS3 binding loci frequently located near those of hepatocyte nuclear factor 1-Beta (HNF1B) and nuclear respiratory factor 1 (NRF1) suggesting GLIS3 regulates transcription of many metabolic and mitochondrial function-related genes in coordination with these TFs. Seahorse analysis and untargeted metabolomics corroborated that mitochondrial OXPHOS utilization is suppressed in GLIS3-deficient kidneys and showed that key metabolites in glycolysis, TCA cycle, and glutamine pathways were altered indicating increased reliance on aerobic glycolysis and glutamine anaplerosis. These features of metabolic reprogramming may contribute to a bioenergetic environment that supports renal cyst formation and progression in Glis3-deficient mice kidneys.CONCLUSIONS: We identify GLIS3 as a novel positive regulator of the transition from aerobic glycolysis to OXPHOS in normal early postnatal kidney development by directly regulating the transcription of mitochondrial metabolic genes. Loss of GLIS3 induces several features of renal cell metabolic reprogramming. Our study identifies GLIS3 as a new participant in an interconnected transcription regulatory network, that includes HNF1B and NRF1, critical in the regulation of mitochondrial-related gene expression and energy metabolism in normal postnatal kidneys and PKD pathogenesis in Glis3-deficient mice.PMID:39505148 | DOI:10.1016/j.molmet.2024.102052

Metab Eng. 2024 Nov 4:S1096-7176(24)00144-7. doi: 10.1016/j.ymben.2024.11.002. Online ahead of print.ABSTRACTEngineering of a specialized metabolic pathway in plants is a promising approach to produce high-value bioactive compounds to address the challenges of climate change and population growth. Understanding the interaction between the heterologous pathway and the native metabolic network of the host plant is crucial for optimizing the engineered system and maximizing the yield of the target compound. In this study, we performed transcriptomic, metabolomic and metagenomic analysis of tobacco (Nicotiana tabacum) plants engineered to produce betanin, an alkaloid pigment that is found in Caryophyllaceae plants. Our data reveals that, in a dose-dependent manor, the biosynthesis of betanin promotes carbohydrate metabolism and represses nitrogen metabolism in the leaf, but enhances nitrogen assimilation and metabolism in the root. By supplying nitrate or ammonium, the accumulation of betanin increased by 1.5∼3.8-fold in leaves and roots of the transgenic plants, confirming the pivotal role of nitrogen in betanin production. In addition, the rhizosphere microbial community is reshaped to reduce denitrification and increase respiration and oxidation, assistant to suppress nitrogen loss. Our analysis not only provides a framework for evaluating the pleiotropic effects of an engineered metabolic pathway on the host plant, but also facilitates the development of novel strategies to balance the heterologous process and the native metabolic network for the high-yield and nutrient-efficient production of bioactive compounds in plants.PMID:39505140 | DOI:10.1016/j.ymben.2024.11.002

Environ Pollut. 2024 Nov 4:125246. doi: 10.1016/j.envpol.2024.125246. Online ahead of print.ABSTRACTNanoplastics (NPs) can adversely affect living organisms. However, the uptake of NPs by plants and the physiological and molecular mechanisms underlying NP-mediated plant growth remain unclear, particularly in the presence of iron minerals and humic acid (HA). In this study, we investigated NP accumulation in rice (Oryza sativa L.) and the physiological effects of exposure to polystyrene NPs (0, 20, and 100 mg L-1) in the presence of iron plaque (IP) and HA. NPs were absorbed on the root surface and entered cells, and confocal laser scanning microscopy confirmed NP uptake by the roots. NP treatments decreased root superoxide dismutase (SOD) activity (28.9-44.0%) and protein contents (31.2-38.6%). IP and HA (5 and 20 mg L-1) decreased the root protein content (20.44-58.3% and 44.2-45.2%, respectively) and increased the root lignin content (22.3-27.5% and 19.2-29.6%, respectively) under NP stress. IP inhibited the NP-induced decreasing trend of SOD activity (19.2-29.5%), while HA promoted this trend (48.7-50.3%). Transcriptomic and metabolomic analysis (Control, 100NPs, and IP-100NPs-20HA) showed that NPs inhibited arginine biosynthesis, and alanine, aspartate, and glutamate metabolism and activated phenylpropanoid biosynthesis related to lignin. The coexistence of IP and HA had positive effects on the amino acid metabolism and phenylpropanoid biosynthesis induced by NPs. Regulation of genes and metabolites involved in nitrogen metabolism and secondary metabolism significantly altered the levels of protein and lignin in rice roots. These findings provide a scientific basis for understanding the environmental risk of NPs under real environmental conditions.PMID:39505096 | DOI:10.1016/j.envpol.2024.125246

Microb Pathog. 2024 Nov 4:107048. doi: 10.1016/j.micpath.2024.107048. Online ahead of print.ABSTRACTHuman adenovirus type 7 (HAdV-7) is a prominent pathogen that causes severe pneumonia in children in China. However, the interaction between HAdV-7 infection and host metabolism is still poorly understood. To gain a comprehensive understanding of the metabolic interplay between host cells and the virus, we analysed the energy and lipid metabolism profiles of the HAdV-7-infected lung cancer cell line A549 by ultrahigh-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (ESI-QTRAP-MS/MS). Our study revealed significant alterations in various metabolic processes, including the tricarboxylic acid cycle, purine and pyrimidine metabolism, amino acid metabolism, nucleotide metabolism, and lipid metabolism, in A549 cells after HAdV-7 infection. Moreover, HAdV-7 infection stimulated enhanced synthesis of membrane lipids in A549 cells. These findings emphasize the crucial role of metabolism in viral infection and suggest that modulating host cell metabolism could be a promising approach for targeted drug development and infection control.PMID:39505087 | DOI:10.1016/j.micpath.2024.107048

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