PubMed
The human plasma lipidome response to exertional heat tolerance testing
Lipids Health Dis. 2024 Nov 15;23(1):380. doi: 10.1186/s12944-024-02322-7.ABSTRACTBACKGROUND: The year of 2023 displayed the highest average global temperatures since it has been recorded-the duration and severity of extreme heat are projected to increase. Rising global temperatures represent a major public health threat, especially to occupations exposed to hot environments, such as construction and agricultural workers, and first responders. Despite efforts of the scientific community, there is still a need to characterize the pathophysiological processes leading to heat related illness and develop biomarkers that can predict its onset.METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based lipidomics analysis was performed on plasma from male and female subjects who underwent exertional heat tolerance testing (HTT), consisting of a 2-h treadmill walk at 5 km/h with 2.0% incline at a controlled temperature of 40ºC. From HTT, heat tolerance was calculated using the physiological strain index (PSI).RESULTS: Nearly half of all 995 detected lipids from 27 classes were responsive to HTT. Lipid classes related to substrate utilization were predominantly affected by HTT, with a downregulation of triacylglycerols and upregulation of free fatty acids and acyl-carnitines (CARs). Even chain CAR 4:0, 14:0 and 16:1, suggested by-products of incomplete beta oxidation, and diacylglycerols displayed the highest correlation to PSI. PSI did not correlate with plasma lactate levels, suggesting that correlations between even chain CARs and PSI are related to metabolic efficiency versus physical exertion.CONCLUSIONS: Overall, HTT displays a strong impact on the human plasma lipidome and lipid metabolic inefficiencies may underlie reduced heat tolerance.PMID:39548465 | DOI:10.1186/s12944-024-02322-7
Study on gut microbiota and metabolomics in postmenopausal women
BMC Womens Health. 2024 Nov 15;24(1):608. doi: 10.1186/s12905-024-03448-7.ABSTRACTMenopausal syndrome, occurring during the menopausal stage in women, manifests as symptoms stemming from decreased estrogen levels, such as hot flashes, insomnia, mental disorders (anxiety, depression), and osteoporosis. The bulk of studies have indicated alterations in the gut microbiota of those experiencing menopause syndrome compared to healthy women. However, This article focuses on the alterations in gut microbiota in perimenopausal women. Our study utilized 16 s rRNA sequencing to determine the differences in the gut microbiota and metabolites among 44 menopausal syndrome women. The distribution of gut microbiota in postmenopausal women varies based on the level of follicle stimulating hormone, with changes in gut microbiota abundance taking precedence over symptom onset. Fecal metabolites reveal changes in several metabolites, including Amino acid metabolism (Tyrosine, Tryptophan), Lipid metabolism (Alpha linolenic acid metabolism), and other metabolites. Disturbances in lipid metabolism, triggered by hormonal level fluctuations, can contribute to the development of osteoporosis.PMID:39548431 | DOI:10.1186/s12905-024-03448-7
Multi-tissue metabolomic profiling reveals the crucial metabolites and pathways associated with scallop growth
BMC Genomics. 2024 Nov 15;25(1):1091. doi: 10.1186/s12864-024-11016-4.ABSTRACTBACKGROUND: Bivalves represent a vital economic resource in aquaculture for their high productivity and extensive market demand. Growth is one of the most important and desired aquaculture traits for bivalves, regulated by multiple levels, notably intricate metabolic processes. However, the understanding of the metabolic profiles that influence bivalve growth is limited, particularly from a multi-tissue perspective.RESULTS: In this study, metabolic profiles of multiple tissues of Chlamys farreri with different growth performance were systematically investigated by ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Through comparing the metabolic variation between fast-growing (FG) scallops and slow-growing (SG) scallops, 613, 509, 105, and 192 significantly different metabolites (SDMs) were identified in the mantle, gill, adductor muscle, and digestive gland, respectively. Growth-related metabolic pathways including sphingolipid metabolism, fatty acid biosynthesis, and ABC transporter pathway, along with 11 SDMs associated with growth traits were identified in all four tissues, implying they were involved in the growth of multiple tissues in scallops. Tissue-specific metabolic profiling indicated that sulfur-containing amino acid metabolism in the mantle potentially contributed to shell growth, while the gill synergistically participated with the mantle through various metabolic processes, such as tyrosine metabolism, glycine, serine, and threonine metabolism and melanogenesis; energy metabolism was crucial for adductor muscle growth; and nutrients digestion and absorption in the digestive gland were linked to scallop growth.CONCLUSIONS: Our results represent the first comprehensive analysis of the crucial pathways and metabolites associated with the growth of C. farreri, offering valuable insights for future bivalve aquaculture production.PMID:39548384 | DOI:10.1186/s12864-024-11016-4
Comparative metabolic profiling and quantitative analysis of metabolites in different tissues of Ajuga turkestanica by ESI-UHPLC-QqTOF-MS and NMR
Sci Rep. 2024 Nov 15;14(1):28179. doi: 10.1038/s41598-024-71546-5.ABSTRACTAjuga turkestanica preparations are used as anti-aging cosmeceuticals and for medicinal purposes. Herein we describe the characterization and quantification of its metabolites in different organs using UHPLC-MS and NMR spectroscopy. A total of 51 compounds belonging to various phytochemical classes (11 flavonoids, 10 ecdysteroids, 9 diterpenes, 6 fatty acids, 5 iridoids, 3 phenylpropanoids, 3 sugars, 2 phenolics, 1 coumarin, 1 triterpene) were annotated and tentatively identified by UHPLC-ESI-QqTOF-MS/MS of methanolic extracts obtained separately from the organs. 1D and 2D NMR spectroscopy independently confirmed the identity of six major compounds. The abundances of these main constituents in flowers, fruits, leaves, roots, seeds, and stems were compared and quantified using 1H NMR. The results showed that 8-O-acetylharpagide, 20-hydroxyecdysone (ecdysterone) and ajugachin B were the most abundant constituents in the species. The two major compounds, 8-O-acetylharpagide and 20-hydroxyecdysone, were chosen as the markers for the quality assessment of A. turkestanica material. The methanolic extract of the aerial parts of A. turkestanica showed no noteworthy anthelmintic (antihelmintic), antifungal, or cytotoxic effect in in vitro assays.PMID:39548128 | DOI:10.1038/s41598-024-71546-5
Metabolites from intact phage-infected Synechococcus chemotactically attract heterotrophic marine bacteria
Nat Microbiol. 2024 Nov 15. doi: 10.1038/s41564-024-01843-2. Online ahead of print.ABSTRACTChemical cues mediate interactions between marine phytoplankton and bacteria, underpinning ecosystem-scale processes including nutrient cycling and carbon fixation. Phage infection alters host metabolism, stimulating the release of chemical cues from intact plankton, but how these dynamics impact ecology and biogeochemistry is poorly understood. Here we determine the impact of phage infection on dissolved metabolite pools from marine cyanobacteria and the subsequent chemotactic response of heterotrophic bacteria using time-resolved metabolomics and microfluidics. Metabolites released from intact, phage-infected Synechococcus elicited strong chemoattraction from Vibrio alginolyticus and Pseudoalteromonas haloplanktis, especially during early infection stages. Sustained bacterial chemotaxis occurred towards live-infected Synechococcus, contrasted by no discernible chemotaxis towards uninfected cyanobacteria. High-throughput microfluidics identified 5'-deoxyadenosine and 5'-methylthioadenosine as key attractants. Our findings establish that, before lysis, phage-infected picophytoplankton release compounds that attract motile heterotrophic bacteria, suggesting a mechanism for resource transfer that might impact carbon and nutrient fluxes across trophic levels.PMID:39548345 | DOI:10.1038/s41564-024-01843-2
Single cell-spatial transcriptomics and bulk multi-omics analysis of heterogeneity and ecosystems in hepatocellular carcinoma
NPJ Precis Oncol. 2024 Nov 15;8(1):262. doi: 10.1038/s41698-024-00752-1.ABSTRACTThis study profiled global single cell-spatial-bulk transcriptome landscapes of hepatocellular carcinoma (HCC) ecosystem from six HCC cases and a non-carcinoma liver control donor. We discovered that intratumoral heterogeneity mainly derived from HCC cells diversity and pervaded the genome-transcriptome-proteome-metabolome network. HCC cells are the core driving force of taming tumor-associated macrophages (TAMs) with pro-tumorigenic phenotypes for favor its dominant growth. Remarkably, M1-types TAMs had been characterized by disturbance of metabolism, poor antigen-presentation and immune-killing abilities. Besides, we found simultaneous cirrhotic and HCC lesions in an individual patient shared common origin and displayed parallel clone evolution via driving disparate immune reprograms for better environmental adaptation. Moreover, endothelial cells exhibited phenotypically conserved but executed differential functions in a space-dependent manner. Further, the spatiotemporal traits of rapid recurrence niche genes were identified and validated by immunohistochemistry. Our data unravels the great significance of HCC cells in shaping vibrant tumor ecosystems corresponding to clinical scenarios.PMID:39548284 | DOI:10.1038/s41698-024-00752-1
Estrogen-mediated inhibition of purine metabolism and cell cycle arrest as a novel therapeutic approach in colorectal cancer
Mol Cell Endocrinol. 2024 Nov 13:112414. doi: 10.1016/j.mce.2024.112414. Online ahead of print.ABSTRACTPurine metabolism is upregulated in various cancers including colorectal cancer (CRC). While previous work has elucidated the role of estrogen (E2) in metabolic reprogramming and ATP production, the effect of E2 on purine metabolism remains largely unknown. Herein, the impact of E2 signalling on purine metabolism in CRC cells was investigated using metabolome and transcriptome profiling of cell extracts derived from E2-treated HCT-116 cells with intact or silenced estrogen receptor alpha (ERα). Purine metabolic pathway enrichment analysis showed that 27 genes in the de novo purine synthesis pathway were downregulated in E2-treated CRC cells. Downstream consequences of E2 treatment including the induction of DNA damage, cell cycle arrest, and apoptosis were all shown to be ERα-dependent. These findings demonstrate, for the first time, that E2 exerts a significant anti-growth and survival effect in CRC cells by targeting the purine synthesis pathway in a ERα-dependent manner, meriting further investigation of the therapeutic utility of E2 signalling in CRC.PMID:39547645 | DOI:10.1016/j.mce.2024.112414
Integrating nontargeted metabolomics and RNA sequencing of dexamethasone-treated and untreated asthmatic mice reveals changes of amino acids and aminoacyl-tRNA in group 2 innate lymphoid cells
Int J Biol Macromol. 2024 Nov 13:137630. doi: 10.1016/j.ijbiomac.2024.137630. Online ahead of print.ABSTRACTBronchial asthma is the most common multifactorial and heterogeneous disease in childhood. The glucocorticoid dexamethasone is a classic treatment for asthma. Research indicates that group 2 innate lymphoid cells (ILC2s) are crucial to the pathogenesis of asthma. However, few studies have focused on ILC2s metabolism and transcription. This study aims to establish an ovalbumin (OVA)-induced asthma model and a dexamethasone-treated asthma model to explore the regulation of lung ILC2s at the genetic and metabolic levels during the progression and remission of asthma, utilizing single-cell metabolomics and transcriptomics approaches. The results showed that ILC2s regulated the metabolic pathways and transcriptional levels of amino acids (such as arginine, proline, and histidine) and linoleic acid, as well as the metabolic biomarkers of arginine, urocanic acid, and linoleic acid in asthma. Additionally, the cytokine pathways and NF-γB pathways have been altered at the genetic level. At the same time, we revealed that dexamethasone regulates ILC2s amino acid and aminoacyl tRNA metabolism, as well as related genes, thereby alleviating asthma symptoms. Furthermore, we identified the genes Eno3 and Tap1, which are significantly associated with asthma. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the accuracy of the RNA sequencing results. This study, for the first time, revealed the mechanistic changes of ILC2s in the development and treatment of asthma using multiomics techniques, laying a foundation for targeted therapies in asthma.PMID:39547613 | DOI:10.1016/j.ijbiomac.2024.137630
PCSK9 in metabolism and diseases
Metabolism. 2024 Nov 13:156064. doi: 10.1016/j.metabol.2024.156064. Online ahead of print.ABSTRACTPCSK9 is a serine protease that regulates plasma levels of low-density lipoprotein (LDL) and cholesterol by mediating the endolysosomal degradation of LDL receptor (LDLR) in the liver. When PCSK9 functions unchecked, it leads to increased degradation of LDLR, resulting in elevated circulatory levels of LDL and cholesterol. This dysregulation contributes to lipid and cholesterol metabolism abnormalities, foam cell formation, and the development of various diseases, including cardiovascular disease (CVD), viral infections, cancer, and sepsis. Emerging clinical and experimental evidence highlights an imperative role for PCSK9 in metabolic anomalies such as hypercholesterolemia and hyperlipidemia, as well as inflammation, and disturbances in mitochondrial homeostasis. Moreover, metabolic hormones - including insulin, glucagon, adipokines, natriuretic peptides, and sex steroids - regulate the expression and circulatory levels of PCSK9, thus influencing cardiovascular and metabolic functions. In this comprehensive review, we aim to elucidate the regulatory role of PCSK9 in lipid and cholesterol metabolism, pathophysiology of diseases such as CVD, infections, cancer, and sepsis, as well as its pharmaceutical and non-pharmaceutical targeting for therapeutic management of these conditions.PMID:39547595 | DOI:10.1016/j.metabol.2024.156064
Leonurine restrains granulosa cell ferroptosis through SLC7A11/GPX4 axis to promote the treatment of polycystic ovary syndrome
Free Radic Biol Med. 2024 Nov 13:S0891-5849(24)01055-4. doi: 10.1016/j.freeradbiomed.2024.11.021. Online ahead of print.ABSTRACTPolycystic ovary syndrome (PCOS) is a common endocrine disorder marked by ovarian dysfunction and metabolic abnormality. This study explores the therapeutic potential of leonurine (SCM-198) in PCOS. Our results show that SCM-198 treatment significantly improved ovarian function, hormone disorders and insulin resistance while reducing granulosa cell ferroptosis. This study provides the first evidence that SCM-198 modulates the gut microbiota composition, increases the abundance of Christensenella minuta, and boosts butyrate levels. Transcriptomic and metabolomic analyses revealed that PCOS patients exhibit granulosa cell ferroptosis and decreased butyrate levels in follicular fluid. Butyrate was shown to alleviate ferroptosis in granulosa cells via the SLC7A11/TXNRD1/GPX4 pathway, as confirmed in vitro with KGN cells. The therapeutic mechanism of SCM-198 in the management of PCOS via the gut-ovary axis involves the enhancement of intestinal microbiota and its metabolites. This intervention improves ovarian function and alleviates PCOS symptoms by targeting ferroptosis in granulosa cells.PMID:39547522 | DOI:10.1016/j.freeradbiomed.2024.11.021
CRISPR-Cas9 mediated knockout of NDUFS4 in human iPSCs: A model for mitochondrial complex I deficiency
Biochim Biophys Acta Mol Basis Dis. 2024 Nov 13:167569. doi: 10.1016/j.bbadis.2024.167569. Online ahead of print.ABSTRACTMitochondrial diseases, often caused by defects in complex I (CI) of the oxidative phosphorylation system, currently lack curative treatments. Human-relevant, high-throughput drug screening platforms are crucial for the discovery of effective therapeutics, with induced pluripotent stem cells (iPSCs) emerging as a valuable technology for this purpose. Here, we present a novel iPSC model of NDUFS4-related CI deficiency that displays a strong metabolic phenotype in the pluripotent state. Human iPSCs were edited using CRISPR-Cas9 to target the NDUFS4 gene, generating isogenic NDUFS4 knockout (KO) cell lines. Sanger sequencing detected heterozygous biallelic deletions, whereas no indel mutations were found in isogenic control cells. Western blotting confirmed the absence of NDUFS4 protein in KO iPSCs and CI enzyme kinetics showed a ~56 % reduction in activity compared to isogenic controls. Comprehensive metabolomic profiling revealed a distinct metabolic phenotype in NDUFS4 KO iPSCs, predominantly associated with an elevated NADH/NAD+ ratio, consistent with alterations observed in other models of mitochondrial dysfunction. Additionally, β-lapachone, a recognized NAD+ modulator, alleviated reductive stress in KO iPSCs by modifying the redox state in both the cytosol and mitochondria. Although undifferentiated iPSCs cannot fully replicate the complex cellular dynamics of the disease seen in vivo, these findings highlight the utility of iPSCs in providing a relevant metabolic milieu that can facilitate early-stage, high-throughput exploration of therapeutic strategies for mitochondrial dysfunction.PMID:39547516 | DOI:10.1016/j.bbadis.2024.167569
Integrative network pharmacology and multi-omics to study the potential mechanism of Niuhuang Shangqing Pill on acute pharyngitis
J Ethnopharmacol. 2024 Nov 13:119100. doi: 10.1016/j.jep.2024.119100. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Niuhuang Shangqing Pill (NSP) is a renowned Chinese medicine prescription listed in the Chinese Pharmacopoeia (Edition 2020, volume 1) and is utilized in clinical practice for treating headaches and acute pharyngitis (AP) associated with "Shanghuo". Despite its widespread use, the pharmacological mechanism and bioactive components underlying NSP in treating AP remain unclear.AIM OF THE STUDY: This study delved into evaluate the alleviation effect of NSP on AP and explore the mechanisms by analyzing multi-omics.MATERIALS AND METHODS: UHPLC-Q Exactive Orbitrap HRMS was employed for the chemical ingredients of NSP. Multiple compositions, targets and pathways involved in the treatment of AP with NSP were predicted by network pharmacology. Additionally, wistar rat model of AP induced by capsaicin was established to evaluate the anti-AP activity of NSP in vivo. The potential mechanism of NSP to improve AP was investigated by real-time PCR, pharyngeal transcriptome analysis, non-targeted metabolomics, immunofluorescence and western blot.RESULTS: 119 compounds were identified by UHPLC-Q Exactive Orbitrap HRMS. Both clinical data of Gene Expression Omnibus (GEO) and network pharmacology demonstrated that MAPK signaling pathway and TNF signaling pathway were the critical pathway for AP treatment. In rat model of AP induced by capsaicin, NSP demonstrated the ability to reduce the levels of IL-1β, TNF-α, IL-6, CGRP, SP, PGE2, COX-2 in serum. Moreover, Transcriptomics analysis comprehensively indicated that NSP regulated the MAPK signaling pathway, TNF signaling pathway, biosynthesis of phenylalanine, tyrosine and tryptophan, arachidonic acid metabolism in AP rats. Metabolomics analysis verified that NSP could rebalance arachidonic acid metabolism, biosynthesis of phenylalanine, tyrosine and tryptophan and regulate metabolic profiles. Multi-omics Correlation analysis exhibited that the relative expression of Tnfrsf1b was significantly negatively correlated with 12(S)-HPETE. Immunofluorescence, real-time PCR and western blot of pharyngeal tissue revealed that NSP inhibited the TNF/p38-MAPK/NF-κB signaling pathway. Additionally, in vitro study on RAW264.7 cells confirmed that NSP counteract LPS-induced inflammatory by inhibiting the TNF/p38-MAPK/NF-κB signaling pathway. Overall, NSP effectively ameliorated capsaicin-induced AP by modulating the arachidonic acid metabolism and TNF/p38-MAPK/NF-κB signaling pathway.CONCLUSION: NSP effectively ameliorated capsaicin-induced AP by modulating the arachidonic acid metabolism, biosynthesis of phenylalanine, tyrosine and tryptophan, as well as the TNF/p38-MAPK/NF-κB signaling pathway.PMID:39547363 | DOI:10.1016/j.jep.2024.119100
Comparative transcriptomic and metabolomic analysis of FTO knockout and wild-type porcine iliac artery endothelial cells
Gene. 2024 Nov 13:149094. doi: 10.1016/j.gene.2024.149094. Online ahead of print.ABSTRACTThe fat mass and obesity associated (FTO) gene, previously identified as a pivotal genetic locus associated with adiposity, has recently been linked to various cancers. In this study, we established an FTO knockout (KO) cell line in porcine iliac artery endothelial cells (PIECs) utilizing CRISPR/Cas9 technology to systematically investigate the gene's function and effect through transcriptomic and metabolomic analysis. Our results revealed significant gene expression and metabolic profiles differences between the FTO KO and wild-type (WT) cells. Furthermore, enrichment analysis highlighted the involvement of differentially expressed genes in metabolic processes, cellular components, and molecular functions, as well as in complement and coagulation cascades, mineral absorption, glutathione metabolism, insulin signaling, fluid shear stress, and atherosclerosis pathways. The metabolomic profiling revealed clear distinctions between the FTO KO and WT cells, indicating profound modifications in cellular metabolism. Correlation analysis of transcriptomic and metabolomic data revealed a significant association between six metabolites and twenty genes, with melatonin showing specific correlations with the expression of several genes, indicating a complex regulatory network between gene expression and metabolic changes. This study provides a foundation for further research on the FTO gene's role in cellular processes and molecular mechanisms underlying physiological and pathological conditions.PMID:39547360 | DOI:10.1016/j.gene.2024.149094
Metabolomics and transcriptomics analysis reveals the enhancement of growth, anti-oxidative stress and immunity by (-)-epigallocatechin-3-gallate in Litopenaeus vannamei
Fish Shellfish Immunol. 2024 Nov 13:110025. doi: 10.1016/j.fsi.2024.110025. Online ahead of print.ABSTRACT(-)-epigallocatechin-3-gallate (EGCG), the main active component of tea polyphenols, has been less studied in Litopenaeus vannamei. Therefore, the potential benefits of EGCG on L. vannamei were explored in this experiment. L. vannamei were fed diets containing EGCG (0, 0.5, and 1.0 g/kg). At the end of the 60-day farming experiment, metabolomics, transcriptomics, quantitative real-time PCR assays, and tissue sections were used to assess and explore the effects of EGCG on growth, antioxidant capacity, and immunity. It was found that the best growth and genes expressions related to antioxidant, anti-stress, apoptosis, and immunity were observed in the group with 0.5 g/kg EGCG. The analysis of hepatopancreatic metabolomics and transcriptomics results revealed bumper differential metabolites and differentially expressed genes (DEGs) associated with nutrient metabolism, digestion, immunity, and environmental adaptation. Many metabolites with anti-inflammatory, antibacterial, antiviral, and antioxidant activities have been identified. A large number of DEGs were enriched in apoptosis, Rap1 signaling pathway, HIF-1 signaling pathway, hippo signaling pathway, chemokine signaling pathway, and signaling pathways related to amino acid and lipid metabolism. In conclusion, dietary 0.5 g/kg EGCG was beneficial for growth, resistance to oxidative stress, and immunity in L. vannamei. The improvement of the properties was attributed to the modulation of signaling pathways, metabolites abundance and genes expressions related to the above properties by EGCG.PMID:39547270 | DOI:10.1016/j.fsi.2024.110025
Itaconate promotes an unexpected tumor immune escape mechanism
Cancer Cell. 2024 Oct 30:S1535-6108(24)00399-4. doi: 10.1016/j.ccell.2024.10.011. Online ahead of print.ABSTRACTItaconate is a metabolite produced by macrophages upon infection and acts as an antimicrobial molecule. In this issue of Cancer Cell, Lin et al. found that itaconate produced by tumor-associated macrophages is taken up by cancer cells via the transporter solute carrier family 13 member 3 (SLC13A3), promoting resistance to immune checkpoint inhibitors.PMID:39547232 | DOI:10.1016/j.ccell.2024.10.011
Metabolomic profiling identifies signatures and biomarkers linking air pollution to dementia risk: A prospective cohort study
J Hazard Mater. 2024 Nov 13;480:136498. doi: 10.1016/j.jhazmat.2024.136498. Online ahead of print.ABSTRACTExposure to air pollution has been associated with increased dementia. However, it remains unknown what specific metabolic mechanisms play a role in this relationship. We included 192,300 dementia-free participants from the UK Biobank cohort study. Annual concentrations of air pollution were assessed based on the residential address. Elastic net regression was performed to identify air pollution-related metabolites, and metabolic score was constructed. Cox regression models and covariate balancing generalized propensity scores (CBGPS) regression models were conducted to explore the longitudinal associations between air pollution/metabolic signatures and dementia risk. The underlying mechanisms between air pollution and dementia driven by metabolic signature or specific metabolites were also investigated. A total of 2592 incident dementia cases were documented. We identified the metabolite profiles in response to air pollution exposure, including 87 metabolites for PM2.5, 65 metabolites for PM10, 76 metabolites for NO2, and 71 metabolites for NOx. The air pollution-related metabolic signatures were associated with increased risk of dementia, with hazard ratios (HR) of 1.17 (95 % CI: 1.12, 1.22), 1.06 (95 % CI: 1.02, 1.11), 1.16 (95 % CI: 1.10, 1.21), and 1.17 (95 % CI: 1.12, 1.22) for PM2.5, PM10, NO2 and NOx, respectively. The associations persisted using causal models. Metabolic signatures mediated the associations between air pollution exposure and dementia risk, with mediation proportions ranging from 6.57 % to 12.71 %. Additionally, we observed that a metabolite known as free cholesterol in medium VLDL (M-VLDL-FC) played a crucial mediating role. Our study provides novel insights into the metabolic mechanisms linking air pollution exposure to dementia risk.PMID:39547039 | DOI:10.1016/j.jhazmat.2024.136498
Untargeted metabolomics reveals the formation pathways of bound sulfite in sodium metabisulfite-soaked Hemerocallis citrina Baroni
Food Chem. 2024 Nov 6;465(Pt 1):141927. doi: 10.1016/j.foodchem.2024.141927. Online ahead of print.ABSTRACTHemerocallis citrina Baroni (HC) is usually soaked with sodium metabisulfite solution after harvest to keep its freshness. However, this will introduce bound sulfites with potential safety risks. In this study, formation pathways of bound sulfite in HC were explored using ultra-high performance liquid chromatography-Q-Exactive HF mass spectrometry (UHPLC-QE-MS) and statistical analysis. The results indicated that the chemical composition of HC changed the most at soaking times of 6-8 h and concentrations of 1.00-2.50 mg/mL. Primary metabolites and phenols in secondary metabolites were greatly affected during soaking. 71 compounds were identified in HC and 8 characteristic markers including 3 bound sulfites were screened which can be used to distinguish between non-soaked HC (NSHC) and sodium metabisulfite-soaked HC (SSHC). Among the 19 commercial HC samples analyzed, 79 % had been treated with sulfites. Mass spectrometry data further revealed two pathways of formation of bound sulfite in HC: one is the sulfonation of amino acids at the amino, the content initially increased with sulfite soaking time and concentration and then decreased until it disappeared; the other is that the addition of aldehyde at the carbonyl, the content increased continuously with sulfite soaking concentration. This study provides insight into bound sulfite formation in HC post‑sodium metabisulfite treatment.PMID:39546989 | DOI:10.1016/j.foodchem.2024.141927
Grapevine and maize: Two guard cell shaped strategies to cope with repeated drought stress
Plant Physiol Biochem. 2024 Nov 7;217:109262. doi: 10.1016/j.plaphy.2024.109262. Online ahead of print.ABSTRACTAdaptation of crops to recurrent drought stress is crucial for maintaining agricultural productivity and achieving food security under changing climate. Guard cells, pivotal regulators of plant water usage and assimilation, are central to this adaptation process. However, the metabolic dynamics of guard cells under drought stress remain poorly understood, particularly in grapevine, a prominent crop grown in arid regions, and maize, a staple crop with substantial water requirements. In this study, differences in guard cells metabolism during drought stress of grapevine and maize were investigated by performing physiological and metabolomic analyses. Metabolomic analysis highlighted differential responses in amino acids and sugars, with grapevine guard cells displaying greater stability in amino acid and sugar signatures, while maize showed marked increases in sugar levels. These findings suggest two distinct adaptive strategies, a vigorous acclimation of guard cells, as observed in maize, and an attenuated acclimation of guard cells, shown in grapevine. Understanding these metabolic adjustments is helpful for enhancing drought resilience in agricultural systems.PMID:39546948 | DOI:10.1016/j.plaphy.2024.109262
Combined transcriptome and metabolome analysis reveals the mechanism of high nitrite tolerance in freshwater mussel Anodonta woodiana
Comp Biochem Physiol Part D Genomics Proteomics. 2024 Nov 12;52:101359. doi: 10.1016/j.cbd.2024.101359. Online ahead of print.ABSTRACTNitrite contamination and stress on aquatic organisms are increasingly emphasized in freshwater ecosystems. Freshwater bivalves exhibit high tolerance to nitrite; however, the underlying mechanism is unknown. Accordingly, this study investigated the tolerance mechanism of the globally occurring freshwater bivalve Anodonta woodiana. A. woodiana were exposed to nominal concentrations of 0, 250, 500, 1000, 2000, and 4000 mg/L nitrite for 96 h to calculate the 96-h median lethal concentration (96-h LC50). A combined transcriptome and metabolome analysis of the hemolymph (the most vital component of the bivalve immune system) was performed after exposing A. woodiana to 300 mg/L nitrite (approximately half the 96-h LC50) for 96 h. The 96-h LC50 of nitrite in A. woodiana was 618.7 mg/L. Transcriptome analysis identified 5600 differentially expressed genes (DEGs) primarily related to ribosomes, lysosomes, DNA replication, and nucleotide excision repair. Metabolome analysis identified 216 differentially expressed metabolites (DEMs) primarily involved in biosynthesis of amino acids, 2-oxocarboxylic acid metabolism, protein digestion and absorption, aminoacyl-tRNA biosynthesis, nucleotide metabolism, ABC transporters, and valine, leucine and isoleucine degradation. Combined transcriptome and metabolome analysis revealed that DEGs and DEMs were primarily associated with nucleotide (purine and pyrimidine) and amino acid metabolism (including aminoacyl-tRNA biosynthesis, cysteine and methionine metabolism, arginine and proline metabolism, and valine, leucine and isoleucine degradation) as well as the immune system (necroptosis and glutathione metabolism). This study is the first to describe the high tolerance of A. woodiana to nitrite and elucidate the molecular mechanisms underlying high nitrite tolerance in mussels.PMID:39546928 | DOI:10.1016/j.cbd.2024.101359
The impact of different lactobacilli fermentations on secondary metabolites of red raspberry juice and their biotransformation pathways via metabolomics based on UHPLC-MS/MS
Int J Food Microbiol. 2024 Nov 9;427:110974. doi: 10.1016/j.ijfoodmicro.2024.110974. Online ahead of print.ABSTRACTSecondary metabolites are a group of invaluable phytochemicals in raspberries. Fermentation process leads to changes in the phytochemical composition of fruits. This study aimed to investigate the influence of Lacticaseibacillus paracasei subsp. paracasei FBKL1.0328 and Lactiplantibacillus plantarum subsp. plantarum FBKL1.0310 on the secondary metabolites of red raspberry juice (CR) and uncover their conversion pathways via metabolomics based on ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). A total of 695 secondary metabolites in the unfermented and fermented samples were identified. There were 90, 83 and 52 differential secondary metabolites identified in LCR (L. paracasei FBKL1.0328 fermented raspberry juice) vs. CR, LPR (L. plantarum FBKL1.0310 fermented raspberry juice) vs. CR, and LCR vs. LPR, respectively. Certain phenolic acids (e.g. 3-phenyllacitc acid), flavonoids (e.g. galangin-7-glucoside), alkaloids (e.g. indole-3-lactic acid), and terpenoids (e.g. glucosyl 7-methyl-3-methyleneoctane-1,2,6,7-tetraol) were selected as the crucial differential metabolites. These two lactobacilli utilized distinct metabolic pathways for processing secondary metabolites. L. paracasei FBKL1.0328 primarily transformed flavonoids through the "Flavone and flavonol biosynthesis" pathway. L. plantarum FBKL1.0310 mainly converted phenolic acids via the "Tyrosine metabolism" pathway and the "Aminobenzoate degradation" pathway. Interestingly, L. plantarum FBKL1.0310 outperformed L. paracasei FBKL1.0328 in upregulating certain valuable bioactive compounds such as indole-3-lactic acid and 3-phenyllacitc acid, underscoring its potential as a promising strain for developing health-beneficial fermented fruit juices. These findings provide insights to how different lactobacilli modify secondary metabolite composition in red raspberry juice and offer valuable information for the industrial application of lactobacilli in fruit processing.PMID:39546897 | DOI:10.1016/j.ijfoodmicro.2024.110974