PubMed
Investigating the metabolomic pathways in female reproductive endocrine disorders: a Mendelian randomization study
Front Endocrinol (Lausanne). 2024 Oct 31;15:1438079. doi: 10.3389/fendo.2024.1438079. eCollection 2024.ABSTRACTINTRODUCTION: Reproductive endocrine disorders (RED), including polycystic ovary syndrome (PCOS), endometriosis (EMs), and female infertility (FI), significantly affect women's health globally, with varying prevalence across different regions. These conditions can be addressed through medication, surgical interventions, and lifestyle modifications. However, the limited understanding of RED's etiology and the substantial economic burden of its treatment highlight the importance of investigating its pathogenesis. Metabolites play a critical role in metabolic processes and are potentially linked to the development of RED. Despite existing studies suggesting correlations between metabolites and RED, conclusive evidence remains scarce, primarily due to the observational nature of these studies, which are prone to confounding factors.METHODS: This study utilized Mendelian Randomization (MR) to explore the causal relationship between metabolites and RED, leveraging genetic variants associated with metabolite levels as instrumental variables to minimize confounding and reverse causality. Data were obtained from the Metabolomics GWAS Server and the IEU OpenGWAS project. Instrumental variables were selected based on their association with the human gut microbiota composition, and the GWAS summary statistics for metabolites, PCOS, EMs, and FI were analyzed. The MR-Egger regression and random-effects inverse-variance weighted (IVW) methods were employed to validate the causal relationship. Cochran's Q test was employed to evaluate heterogeneity, sensitivity analysis was performed using leave-one-out analysis, and for pleiotropy analysis, the intercept term of MR-Egger's method was investigated.RESULTS: The MR analysis revealed significant associations between various metabolites and RED conditions. For instance, a positive association was found between 1-palmitoylglycerophosphocholine and PCOS, while a negative association was noted between phenylacetate and FI. The study identified several metabolites associated with an increased risk and others with protective effects against PCOS, EMs, and FI. These findings highlight the complex interplay between metabolites and RED, suggesting potential pathways through which these conditions could be influenced or treated.CONCLUSION: This MR study provides valuable insights into the causal relationship between metabolites and female reproductive endocrine disorders, suggesting that metabolic alterations play a significant role in the pathogenesis of PCOS, EMs, and FI, and offering a foundation for future research and therapeutic development.PMID:39544240 | PMC:PMC11560792 | DOI:10.3389/fendo.2024.1438079
The metabolic and physiologic impairments underlying long COVID associated exercise intolerance
Pulm Circ. 2024 Nov 13;14(4):e70009. doi: 10.1002/pul2.70009. eCollection 2024 Oct.ABSTRACTData from invasive CPET (iCPET) revealed long COVID patients have impaired systemic oxygen extraction (EO2), suggesting impaired mitochondrial ATP production. However, it remains uncertain whether the initial severity of SARS-CoV-2 infection has implications on EO2 and exercise capacity (VO2) nor has there been assessment of anerobic ATP generation in long COVID patients. iCPET was performed on 47 long COVID patients (i.e., full cohort; n = 8 with severe SARS-CoV-2 infection). In a subset of patients (i.e., metabolomic cohort; n = 26) metabolomics on venous and arterial blood samples during iCPET was performed. In the full cohort, long COVID patients exhibited reduced peak EO2 with reduced peak VO2 (90 ± 17% predicted) relative to cardiac output (118 ± 23% predicted). Peak VO2 [88% predicted (IQR 81% - 108%) vs. 70% predicted (IQR 64% - 89%); p = 0.02] and EO2 [0.59(IQR 0.53-0.62) vs. 0.53(IQR 0.50-0.48); p = 0.01) were lower in severe versus mild infection. In the metabolomic cohort, 12 metabolites were significantly consumed, and 41 metabolites were significantly released (p-values < 0.05). Quantitative metabolomics demonstrated significant increases in inosine and succinate arteriovenous gradients during exercise. Peak VO2 was significantly correlated with peak venous succinate (r = 0.68; p = 0.0008) and peak venous lactate (r = 0.49; p = 0.0004). Peak EO2 and consequently peak VO2 impact long COVID patients in a severity dependent manner. Exercise intolerance associated with long COVID is defined by impaired aerobic and anaerobic energy production. Peak venous succinate may serve as a potential biomarker in long COVID.PMID:39544193 | PMC:PMC11560803 | DOI:10.1002/pul2.70009
Metabolomic characterization of unintentional weight loss among community-dwelling older Black and White men and women
Aging Cell. 2024 Nov 15:e14410. doi: 10.1111/acel.14410. Online ahead of print.ABSTRACTThis study aims to understand the metabolic mechanisms of unintentional weight loss in older adults. We investigated plasma metabolite associations of subsequent weight change over 2 years in 1536 previously weight stable participants (mean age 74.6 years, 50% women, 35% Black) from the Health, Aging and Body Composition (Health ABC) Study. Multinomial logistic regressions were used to examine associations of the 442 metabolites with weight loss with/without an intention and weight gain >3% annually relative to weight stability. The metabolite associations of unintentional weight loss differed from those of intentional weight loss and weight gain. Lower levels of aromatic amino acids, phospholipids, long-chain poly-unsaturated triglycerides, and higher levels of amino acid derivatives, poly-unsaturated fatty acids, and carbohydrates were associated with higher odds of unintentional weight loss after adjusting for age, sex, race, and BMI categories. Prevalent diseases attenuated four and lower mid-thigh muscle mass and poorer appetite each attenuated 2 of 77 identified metabolite associations by >20%, respectively. Other factors (e.g., energy expenditure, diet, and medication) attenuated all associations by <20%. While 16 metabolite associations were attenuated by 20%-48% when adjusting for all these risk factors, 47 metabolite associations remained significant. Altered amino acid metabolism, impaired mitochondrial fatty acid oxidation, and inflammaging implicated by identified metabolites appear to precede unintentional weight loss in Health ABC older adults. Furthermore, these pathways seem to be associated with prevalent diseases especially diabetes, lower muscle mass, and poorer appetite.PMID:39544124 | DOI:10.1111/acel.14410
UPLC-QTOF-MS based targeted metabolomics to unravel the hepatoprotective marker compounds of Swertia chirayita
Nat Prod Res. 2024 Nov 14:1-6. doi: 10.1080/14786419.2024.2426063. Online ahead of print.ABSTRACTSwertia chirayita is a popular hepatoprotective herb according to 'Ayurveda'. This study characterises the phytochemicals of S. chirayita responsible for hepatoprotective properties was executed using targeted metabolomics approach. Different fractions of hydro-alcoholic extract of S. chirayita were subjected to assess in-vitro antioxidant and hepatoprotective properties in HepG2 cells. Furthermore, active fraction was further subjected to UPLC-QTOF-MS based targeted metabolomics to identify the phytochemicals linked to bioactivity. A complementary in-silico experiment was also performed to understand the interactions of identified molecules with CYP2E1 enzyme. It was observed that, n-butanol fraction deciphers significant (p < .05) and maximum antioxidant and hepatocyte protection compared to other fractions. UPLC-QTOF-HRMS analysis reveals that it contains 17 secondary metabolites various classes. Identified molecules showed potential interactions with the crucial amino acid residues in the active site of CYP2E1 protein indicate the possibility of inhibition which may counter APAP induced toxicity in HepG2 cells.PMID:39544006 | DOI:10.1080/14786419.2024.2426063
F. prausnitzii potentially modulates the association between citrus intake and depression
Microbiome. 2024 Nov 14;12(1):237. doi: 10.1186/s40168-024-01961-3.ABSTRACTBACKGROUND: The gut microbiome modulates the effects of diet on host health, but it remains unclear which specific foods and microbial features interact to influence risk of depression. To understand this interplay, we leveraged decades of dietary and depression data from a longitudinal cohort of women (n = 32,427), along with fecal metagenomics and plasma metabolomics from a substudy (n = 207) nested in this cohort, as well as an independent validation cohort of men (n = 307).RESULTS: We report that citrus intake and its components are prospectively associated with a lower risk of depression and altered abundance of 15 gut microbial species, including enriched Faecalibacterium prausnitzii. In turn, we found a lower abundance of F. prausnitzii and its metabolic pathway, S-adenosyl-L-methionine (SAM) cycle I in participants with depression. To explore causality, we found that lower SAM production by F. prausnitzii may decrease intestinal monoamine oxidase A gene expression implicated in serotonin and dopamine synthesis.CONCLUSIONS: These data underscore the role of diet in the prevention of depression and offer a plausible explanation for how the intestinal microbiome modulates the influence of citrus on mental health. Video Abstract.PMID:39543781 | DOI:10.1186/s40168-024-01961-3
Analysis of variable metabolites in preterm infants with bronchopulmonary dysplasia: a systematic review and meta-analysis
Ital J Pediatr. 2024 Nov 14;50(1):246. doi: 10.1186/s13052-024-01812-9.ABSTRACTNumerous studies have attempted to identify potential biomarkers for early detection of bronchopulmonary dysplasia (BPD) in preterm infants using metabolomics techniques. However, the presence of consistent evidence remains elusive. Our study aimed to conduct a systematic review and meta-analysis to identify differences in small-molecule metabolites between BPD and non-BPD preterm infants. Through meticulous screening of numerous samples, we identified promising candidates, providing valuable insights for future research. We searched PubMed, the Cochrane Library, Embase, Web of Science, China National Knowledge Internet, Wan-fang database, Chinese Science and Technique Journal Database and Chinese Biomedical Literature Database from inception until January 16, 2024. Studies were comprehensively reviewed against inclusion criteria. We included case-control studies and adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Study quality was assessed with the Newcastle-Ottawa scale. We compared the changes in metabolite levels between the BPD and non-BPD preterm infants. A meta-analysis was conducted on targeted metabolomics research data based on the strategy of standardized mean differences (MD) and 95% confidence intervals (CI).Fifteen studies (1357 participants) were included. These clinical-based metabolomics studies clarified 110 differential metabolites between BPD and non-BPD preterm infants. The meta-analysis revealed higher glutamate concentration in the BPD group compared to the non-BPD group (MD = 1, 95% CI 0.59 to 1.41, p < 0.00001). Amino acids were identified as the key metabolites distinguishing preterm infants with and without BPD, with glutamate potentially serving as a BPD predictor in this population.PMID:39543750 | DOI:10.1186/s13052-024-01812-9
An integrated approach for studying exposure, metabolism, and disposition of traditional Chinese medicine using PATBS and MDRB tools: a case study of semen Armeniacae Amarum
Chin Med. 2024 Nov 14;19(1):158. doi: 10.1186/s13020-024-01031-8.ABSTRACTBACKGROUND: Deciphering the in vivo processes of traditional Chinese medicine (TCM) is crucial for identifying new pharmacodynamic substances and new drugs. Due to the complexity and diversity of components, investigating the exposure, metabolism, and disposition remains a major challenge in TCM research. In recent years, a number of non-targeted smart mass-spectrometry (MS) techniques, such as precise-and-thorough background-subtraction (PATBS) and metabolomics, have realized the intelligent identification of in vivo components of TCM. However, the metabolites characterization still largely relies on manual identification in combination with online databases.RESULTS: We developed a scoring approach based on the structural similarity and minimal mass defect variations between metabolites and prototypes. The current method integrates three dimensions of mass spectral data including m/z, mass defect of MS1 and MS2, and the similarity of MS2 fragments, which was sequentially analyzed by a R-based mass dataset relevance bridging (MDRB) data post-processing technique. The MDRB technology constructed a component relationship network for TCM, significantly improving metabolite identification efficiency and facilitating the mapping of translational metabolic pathways. By combining MDRB with PATBS through this non-targeted identification technology, we developed a comprehensive strategy for identification, characterization and bridging analysis of TCM metabolite in vivo. As a proof of concept, we adopted the proposed strategy to investigate the process of exposure, metabolism, and disposition of Semen Armeniacae Amarum (CKXR) in mice.SIGNIFICANCE: The currently proposed analytical approach is universally applicable and demonstrates its effectiveness in analyzing complex components of TCMs in vitro and in vivo. Furthermore, it enables the correlation of in vitro and in vivo data, providing insights into the metabolic transformations among components sharing the same parent nucleus structure. Finally, the developed MDRB platform is publicly available for ( https://github.com/933ZhangDD/MDRB ) for accelerating TCM research for the scientific community.PMID:39543720 | DOI:10.1186/s13020-024-01031-8
Effect of plant-derived microbial soil legacy in a grafting system-a turn for the better
Microbiome. 2024 Nov 14;12(1):234. doi: 10.1186/s40168-024-01938-2.ABSTRACTBACKGROUND: Plant-soil feedback arises from microbial legacies left by plants in the soil. Grafting is a common technique used to prevent yield declines in monocultures. Yet, our understanding of how grafting alters the composition of soil microbiota and how these changes affect subsequent crop performance remains limited. Our experiment involved monoculturing ungrafted and grafted watermelons to obtain conditioned soils, followed by growing the watermelons on the conditioned soils to investigate plant-soil feedback effects.RESULTS: Ungrafted plants grew better in soil previously conditioned by a different plant (heterospecific soil) while grafted plants grew better in soil conditioned by the same plant (conspecific soil). We demonstrated experimentally that these differences in growth were linked to changes in microorganisms. Using a supervised machine learning algorithm, we showed that differences in the relative abundance of certain genera, such as Rhizobium, Chryseobacterium, Fusarium, and Aspergillus, significantly influenced the conspecific plant-soil feedback. Metabolomic analyses revealed that ungrafted plants in heterospecific soil enriched arginine biosynthesis, whereas grafted plants in conspecific soil increased sphingolipid metabolism. Elsewhere, the metagenome-assembled genomes (MAGs) of ungrafted plants identified in heterospecific soil include Chryseobacterium and Lysobacter, microorganisms having been prominently identified in earlier research as contributors to plant growth. Metabolic reconstruction revealed the putative ability of Chryseobacterium to convert D-glucono-1,5-lactone to gluconic acid, pointing to distinct disease-suppressive mechanisms and hence distinct microbial functional legacies between grafted and ungrafted plants.CONCLUSIONS: Our findings show a deep impact of the soil microbial reservoir on plant growth and suggest the necessity to protect and improve this microbial community in agricultural soils. The work also suggests possibilities of optimizing microbiota-mediated benefits through grafting herein, a way that "engineered" soil microbial communities for better plant growth. Video Abstract.PMID:39543707 | DOI:10.1186/s40168-024-01938-2
Metabolomic and transcriptomic analyses reveals candidate genes and pathways involved in secondary metabolism in Bergenia purpurascens
BMC Genomics. 2024 Nov 14;25(1):1083. doi: 10.1186/s12864-024-10953-4.ABSTRACTBergenia purpurascens is an important medicinal, edible and ornamental plant. The lack of omics information hinders the study of its metabolic pathways and related genes. In order to investigate candidate genes and pathways involved in secondary metabolism in B. purpurascens, roots, stems and leaves of B. purpurascens were subjected to metabolomic and transcriptomic analyses in this study. A total of 351 differentially accumulated secondary metabolites were identified. We identified 120 candidate genes involved in phenylpropanoid and flavonoid biosynthesis pathway, from which 29 key candidate genes were obtained by WGCNA. Five UDP-Glycosyltransferases and four O-methyltransferases were suggested to be the candidate enzymes involved in synthetic pathway from gallic acid to bergenin by correlation analysis between transcriptional and metabolic levels and phylogenetic analysis. This study provides data resources and new insights for further studies on the biosynthesis of major active components in B. purpurascens.PMID:39543501 | DOI:10.1186/s12864-024-10953-4
Integrative hyperspectral, transcriptomic, and metabolomic analysis reveals the mechanism of tea plants in response to sooty mold disease
BMC Plant Biol. 2024 Nov 15;24(1):1079. doi: 10.1186/s12870-024-05806-x.ABSTRACTBACKGROUND: Sooty mold (SM), caused by Cladosporium species, is a pervasive threat to tea plant health, affecting both canopy structure and crop yield. Despite its significance, understanding the complex interplay between defense genes and metabolites in tea plants across various SM-infected canopy layers remains limited. Our study employed hyperspectral imaging, transcriptomic profiling, and metabolomic analysis to decipher the intricate mechanisms underlying the tea plant's response to SM infection.RESULTS: Our hyperspectral imaging identified three critical wavelengths (552, 673, and 800 nm) inflection points associated with varying degrees of SM infection. This non-invasive method allows for the precise assessment of disease progression. Concurrently, transcriptome analysis revealed a wealth of differentially expressed genes (DEGs) enriched in metabolic pathways, secondary metabolite biosynthesis, and plant-pathogen interactions. Cluster analysis highlighted an intensified immune response in A2 and A3 samples. A comprehensive metabolomic profile identified 733 co-changed metabolites in SM-infected leaves, with alcohols, lipids (free fatty acids), hydrocarbons, and amino acids significantly accumulating in A1, while flavonoids were predominantly upregulated in A2 and A3. Weighted Gene Co-Expression Network Analysis (WGCNA) uncovered five hub genes (Dormancy-associated protein, Serine/threonine-protein phosphatase, ABC transporter, and some uncharacterized proteins) and two hub metabolites (D-Mannitol and 17-Hydroxylinolenic Acid) that exhibit significant relationships with DEGs and metabolites. Further co-expression analysis indicated that tea plants mainly employed genes and metabolites related to the biosynthesis of secondary metabolites, plant hormone signal transduction, and plant-pathogen interaction to combat SM.CONCLUSION: This study establishes a foundation for understanding the immune mechanisms of tea plants across different canopy layers in response to SM infection. It not only sheds light on the complex defense strategies employed by tea plants but also identifies candidate genes and metabolites crucial for enhancing tea plant breeding and resistance to SM.PMID:39543476 | DOI:10.1186/s12870-024-05806-x
Analysis of metabolites associated with ADIPOQ genotypes in individuals with type 2 diabetes mellitus
Sci Rep. 2024 Nov 15;14(1):28093. doi: 10.1038/s41598-024-79686-4.ABSTRACTDiabetes mellitus (DM) is a significant public health problem and it is known that the identification of molecular markers involved in glycemic control can impact disease control. Although the rs266729 polymorphism located in the promoter of the adiponectin gene (ADP) has been shown to be a candidate for involvement in glycemic control, the genotypic groups have never been characterized in terms of metabolomic aspects. Objective: Analyze the metabolites present in the rs266729 genotype groups. 127 diabetic individuals were compared according to the rs266729 genotype groups CC and GC + GG (RFLP-PCR). Blood plasma metabolites were classified by nuclear magnetic resonance (NMR), and the metabolic pathways of each group using the MetaboAnalyst tool. Insulin therapy (p = 0.049) was more frequent in the GC + GG rs266729 group. Lactate, alanine, glutamine, aspartate, lipid, lysine, isoleucine, citrulline, cholesterol, and fucose impacted the CC group and aspartate, beta-glucose, glutamate, pyruvate, proline, and 2-oxoglutarate impacted the CG + GG group. The glucose-alanine pathway, malate-aspartate transport, and urea cycle impacted the CC group (D-glucose, glutamic acid, L-alanine, oxoglutaric acid, and pyruvic acid). The glutamine/glutamate ratio is likely to be related to the causes of rs266729 influencing the risk of diabetes.PMID:39543306 | DOI:10.1038/s41598-024-79686-4
Longitudinal analyses of infants' microbiome and metabolome reveal microbes and metabolites with seemingly coordinated dynamics
Commun Biol. 2024 Nov 14;7(1):1506. doi: 10.1038/s42003-024-07015-6.ABSTRACTPopulation studies have shown that the infant's microbiome and metabolome undergo significant changes in early childhood. However, no previous study has investigated how diverse these changes are across subjects and whether the subject-specific dynamics of some microbes correlate with the over-time dynamics of specific metabolites. Using mixed-effects models, and data from the ABC study, we investigated the early childhood dynamics of fecal microbiome and metabolome and identified 83 amplicon sequence variants (ASVs) and 753 metabolites with seemingly coordinated trajectories. Enrichment analysis of these microbes and molecules revealed eight ASV families and 23 metabolite groups involving 1032 ASV-metabolite pairs with their presence-absence changing in a coordinated fashion. Members of the Lachnospiraceae (464/1032) and metabolites related to cholestane steroids (309/1032) dominated proportional shifts within the fecal microbiome and metabolome as infants aged.PMID:39543263 | DOI:10.1038/s42003-024-07015-6
p63 affects distinct metabolic pathways during keratinocyte senescence, evaluated by metabolomic profile and gene expression analysis
Cell Death Dis. 2024 Nov 14;15(11):830. doi: 10.1038/s41419-024-07159-7.ABSTRACTUnraveling the molecular nature of skin aging and keratinocyte senescence represents a challenging research project in epithelial biology. In this regard, depletion of p63, a p53 family transcription factor prominently expressed in human and mouse epidermis, accelerates both aging and the onset of senescence markers in vivo animal models as well as in ex vivo keratinocytes. Nonetheless, the biochemical link between p63 action and senescence phenotype remains largely unexplored. In the present study, through ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) and gas chromatography/mass spectrometry (GC/MS) metabolomic analysis, we uncover interesting pathways linking replicative senescence to metabolic alterations during p63 silencing in human keratinocytes. Integration of our metabolomic profiling data with targeted transcriptomic investigation empowered us to demonstrate that absence of p63 and senescence share similar modulation profiles of oxidative stress markers, pentose phosphate pathway metabolites and lyso-glycerophospholipids, the latter due to enhanced phospholipases gene expression profile often under p63 direct/indirect gene control. Additional biochemical features identified in deranged keratinocytes include a relevant increase in lipids production, glucose and pyruvate levels as confirmed by upregulation of gene expression of key lipid synthesis and glycolytic enzymes, which, together with improved vitamins uptake, characterize senescence phenotype. Silencing of p63 in keratinocytes instead, translates into a blunted flux of metabolites through both glycolysis and the Krebs cycle, likely due to a p63-dependent reduction of hexokinase 2 and citrate synthase gene expression. Our findings highlight the potential role of p63 in counteracting keratinocyte senescence also through fine regulation of metabolite levels and relevant biochemical pathways. We believe that our research might contribute significantly to the discovery of new implications of p63 in keratinocyte senescence and related diseases.PMID:39543093 | DOI:10.1038/s41419-024-07159-7
"Elucidating the immunomodulatory role of endocannabinoids in intervertebral disc degeneration"
Eur Spine J. 2024 Nov 14. doi: 10.1007/s00586-024-08550-w. Online ahead of print.ABSTRACTPURPOSE: The endocannabinoid system (ECS) has been well-established to play a crucial role in the regulation of several physiological processes as well as many inflammatory disease conditions. However, its role in intervertebral disc degeneration has been least explored. We aim to investigate the immunomodulatory role of endocannabinoids in regulating IVD health.METHODS: The study population included 20 healthy volunteers (controls) and 40 patients with disc degeneration (disease group) (20 Modic and 20 Non Modic). 16S metagenome sequencing of the V3-V4 region was performed for the DNA extracted from NP tissue samples of both control and disease groups. Sequencing was carried out using the Novaseq 6000 platform using 250 bp paired-end chemistry. A global metabolic profile was obtained using the uHPLC system coupled with Q Exactive Plus Hybrid Quadrupole-Orbitrap mass spectrometer.RESULTS: Our study revealed a higher prevalence of gram-negative bacteria, particularly opportunistic pathogens like Pseudomonas, in diseased discs (71-81%) compared to healthy controls (54%). Further investigation using metabolomics identified significant changes in the lipid profiles of diseased discs. We found that the signalling molecules of the ECS, 2-arachidonylglycerol (2-AG) and N-arachidonoylethanolamine (AEA), were significantly lower in diseased discs compared to controls (Log2FC -2.62 for 2-AG and -3.15 for AEA). Conversely, pro-inflammatory metabolites like LTA4, HPETE, HETE, and Prostaglandin G2 were elevated in diseased discs, with a Log2 fold increase greater than 2.5.CONCLUSION: The study reveals that the endocannabinoid metabolites (2-AG and AEA) of the ECS could be a significant molecule influencing susceptibility to infection and inflammation within the intervertebral discs, which could be a potential target for improving disc health.LEVEL OF EVIDENCE: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.PMID:39542877 | DOI:10.1007/s00586-024-08550-w
Balancing brain metabolic states during sickness and recovery sleep
Eur J Neurosci. 2024 Nov 14. doi: 10.1111/ejn.16588. Online ahead of print.ABSTRACTSickness sleep and rebound following sleep deprivation share humoral signals including the rise of cytokines, in particular interleukins. Nevertheless, they represent unique physiological states with unique brain firing patterns and involvement of specific circuitry. Here, we performed untargeted metabolomics of mouse cortex and hippocampus to uncover changes with sickness and rebound sleep as compared with normal daily sleep. We found that the three settings are biochemically unique with larger differences in the cortex than in the hippocampus. Both sickness and rebound sleep shared an increase in tryptophan. Surprisingly, these two sleep conditions showed opposite modulation of the methionine-homocysteine cycle and differences in terms of the energetic signature, with sickness impinging on glycolysis intermediates whilst rebound increased the triphosphorylated form of nucleotides. These findings indicate that rebound following sleep deprivation stimulates an energy rich setting in the brain that is devoid during sickness sleep.PMID:39542871 | DOI:10.1111/ejn.16588
Characterization of Arabidopsis eskimo1 reveals a metabolic link between xylan O-acetylation and aliphatic glucosinolate metabolism
Physiol Plant. 2024 Nov-Dec;176(6):e14618. doi: 10.1111/ppl.14618.ABSTRACTGlucuronoxylan is present mainly in the dicot of the secondary cell walls, often O-acetylated, which stabilizes cell structure by maintaining interaction with cellulose and other cell wall components. Some members of the Golgi localized Trichome Birefringence-Like (TBL) family function as xylan O-acetyl transferase (XOAT). The primary XOAT in the stem of Arabidopsis is ESKIMO1/TBL29, and its disruption results in decreased xylan acetylation, stunted plant growth, and collapsed xylem vessels. To elucidate the effect on metabolic reprogramming and identify the underlying cause of the stunted growth in eskimo1, we performed transcriptomic, targeted, and untargeted metabolome analysis, mainly in the inflorescence stem tissue. RNA sequencing analysis revealed that the genes involved in the biosynthesis, regulation, and transport of aliphatic glucosinolates (GSLs) were upregulated, whereas those responsible for indolic GSL metabolism were unaffected in the eskimo1 inflorescence stem. Consistently, aliphatic GSLs, such as 4-methylsulfinylbutyl (4MSOB), were increased in stem tissues and seeds. This shift in the profile of aliphatic GSLs in eskimo1 was further supported by the quantification of the soluble acetate, decrease in accumulation of GSL precursor, i.e., methionine, and increase in the level of jasmonic acid.PMID:39542838 | DOI:10.1111/ppl.14618
Microbial pathways contributing to the pathogenesis of rheumatoid arthritis
Semin Arthritis Rheum. 2024 Nov 8:152587. doi: 10.1016/j.semarthrit.2024.152587. Online ahead of print.ABSTRACTNone.PMID:39542790 | DOI:10.1016/j.semarthrit.2024.152587
Combined transcriptomic, metabolomic and physiological analysis reveals the key role of nitrogen, but not phosphate and potassium in regulating anthocyanin biosynthesis induced by nutrient deficiency in Eucalyptus
Int J Biol Macromol. 2024 Nov 12:137564. doi: 10.1016/j.ijbiomac.2024.137564. Online ahead of print.ABSTRACTAnthocyanin biosynthesis in Eucalyptus plants can be flexibly and rapidly modulated in response to hormones or environmental stimuli, including nutrient deprivation (ND). However, the underlying mechanism of ND in inducing anthocyanin biosynthesis in plants remains largely elusive. In this study, we discovered that anthocyanin levels in leaves and stems could well reflect nitrogen availability in Eucalyptus. Supplementation with nitrogen, but not with phosphate or potassium, effectively inhibited ND-induced anthocyanin biosynthesis. To further investigate how nitrogen regulates this process, comprehensive time-resolved transcriptomic and targeted metabolomic analyses were conducted. The results revealed that 3405, 2706, and 3153 genes were differentially regulated by nitrogen treatment at 1, 2, and 3 d, respectively. Pathway analysis indicated the majority of the enriched KEGG pathways were associated with cellular metabolism, such as amino acid and flavonoid biosynthesis. Moreover, metabolomic analysis showed that the most abundantly accumulated anthocyanins, cyanidin-3-O-galactoside and cyanidin-3-O-glucoside, along with key intermediates in the flavonoid pathway, were downregulated by nitrogen treatment. Furthermore, nitrogen-responsive MYB-bHLH-WDR complex genes were identified, including six EgrMYB113 family members. Overexpression of one of the EgrMYB113-like genes induced anthocyanin biosynthesis in the transgenic hairy roots of Eucalyptus. Interestingly, mutation of AtMYB113 inhibited nitrogen deficiency-induced anthocyanin biosynthesis in Arabidopsis, suggesting that MYB113 is a novel N-responsive MYB transcriptional regulator of anthocyanin biosynthesis. Additionally, nitrogen treatment upregulated a few GA biosynthesis genes while simultaneously downregulated the expression of several GA2ox genes. Exogenous application of GA3 decreased ND-induced anthocyanin biosynthesis. Conclusively, this study provides novel insights into the molecular mechanism of nitrogen in the regulation of anthocyanin biosynthesis in Eucalyptus.PMID:39542319 | DOI:10.1016/j.ijbiomac.2024.137564
Hypoglycemic activity of enzymatically extracted Eucommia ulmoides polysaccharide (EUL-w1) on IR-HepG2 cell via the AMPK/PI3K/Akt signaling pathway
Int J Biol Macromol. 2024 Nov 12:137596. doi: 10.1016/j.ijbiomac.2024.137596. Online ahead of print.ABSTRACTThis study devised optimal conditions to extract Eucommia ulmoides leaf (EUL) polysaccharides using a cellulase and pectinase composite enzyme system based on one-way experiments and response surface methodology. Crude EUL polysaccharides (EULPs) were extracted and purified using a DEAE chromatography column. The polysaccharides EUL-w, EUL1, EUL2, and EUL3 were obtained by elution with water, 0.1 mol/L NaCl, 0.2 mol/L NaCl, and 0.3 mol/L NaCl, respectively. The EUL-w fraction had the highest hypoglycemic activity based on its α-amylase and α-glucosidase activities. The preliminary structure of purified EUL-w1 was elucidated. In vitro hypoglycemic activity studies and metabolomics analyses suggested that EUL-w1 modulated glucose metabolism by mediating the AMPK/PI3K/Akt signaling pathway. Our findings provide novel insights and data support for the utilization of EULPs as an emerging food resource in functional foods.PMID:39542294 | DOI:10.1016/j.ijbiomac.2024.137596
Integrated microbial activities and isotope analysis unveil the effects of zinc oxide nanoparticles on straw decomposition in agricultural soil
Sci Total Environ. 2024 Nov 12:177460. doi: 10.1016/j.scitotenv.2024.177460. Online ahead of print.ABSTRACTZinc oxide nanoparticles (ZnONPs) are widely applied across multiple industries and ultimately accumulate in water and soil environments, raising significant concern about their toxicity to organisms in various ecosystems. While the effects of ZnONPs on microflora have been reported, their ecotoxicity to specific biogeochemical process and microbial activities and metabolic functions remains relatively unclear. In this study, a 56-day microcosmic experiment was conducted to explore the toxicity mechanism of ZnONPs (1000 mg kg-1 soil) on straw decomposition, soil organic carbon (SOC) mineralization, and changes in microbial activities and functions in agricultural soil with general wheat straw incorporation using the 13C isotope tracer technique. The results demonstrated that straw incorporation increased the rate of CO2 emission and promoted the straw decomposition. However, the presence of ZnONPs reduced the CO2 release rates during incubation period although the rates were still higher than those under the control due to straw incorporation. CO2 emissions from straw decomposition were dominant before the 7th day of incubation. After day 7, CO2 emissions from the mineralization of original SOC became dominant with their contribution increasing from 17.52 % on day 7 to 60.20 % on day 56 under straw incorporation. ZnONPs affected soil carbon composition and straw decomposition by inhibiting enzyme activity and reducing the abundance of functional genes, indirectly impacting CO2 release. Community Level Physiological Profiles (CLPP) showed ZnONPs reduced functional richness indices, including Shannon-Weiner index (H) and McIntosh index (U), and altered C substrate utilization patterns. This may be due to the direct toxicity of zinc ion (Zn2+) released by ZnONPs to the soil bacterial community. The findings provide insights into the toxicity effects of emerging contaminants on carbon transformation from straw and SOC. Further investigations involving metabolomics are required to reveal the essential effects of ZnONPs on biogeochemical cycle of elements in agricultural soil.PMID:39542265 | DOI:10.1016/j.scitotenv.2024.177460