PubMed

Biochimie. 2024 Dec 5:S0300-9084(24)00293-1. doi: 10.1016/j.biochi.2024.11.015. Online ahead of print.ABSTRACTMicroalgae are active producers of various compounds, including toxic substances. However, their metabolism is very diverse and insufficiently known. We demonstrate an approach that includes growing a new strain of cyanobacterium Leptolyngbya sp. (IPPAS B-1204) on an isotopically labeled medium (D2O) and evaluating the metabolomic composition of these microorganisms after deuterium uptake. Despite the low resolution of the GC-MS method, the interpretation of the obtained spectra allowed us to find out not only the amount of the embedded isotope label but also to assume the position in the structure where the label is embedded. We present the results of reliably detecting more than 30 compounds with isotope labels belonging to various classes of biological compounds produced by this cyanobacterium, revealing the metabolic pathways of entry of this label. We also demonstrate that the synthesis of unsaturated fatty acids is suppressed under the growth on D2O medium. In addition, we found an isotopic effect in the chromatographic separation of isotopically labeled compounds in gas chromatography. These data can be used in the future both for the identification of compounds and the analysis of the biosynthesis pathways of secondary biologically active compounds and in the analysis of the production of isotopically labeled standards of compounds.PMID:39645069 | DOI:10.1016/j.biochi.2024.11.015

Comp Biochem Physiol Part D Genomics Proteomics. 2024 Nov 28;54:101371. doi: 10.1016/j.cbd.2024.101371. Online ahead of print.ABSTRACTWater temperature plays a vital role in shaping the physical conditions crucial for the growth, development and reproduction of fish species. Since limited comprehensive multi-omics analyses exploring the molecular mechanisms of temperature influences on the early life stages of fish. Here, the effects of temperature variations on the growth of Takifugu rubripes, a commercial teleost farmed in Asia were investigated. Nineteen-days-old fugu larvae were subjected to different temperature (15 °C-T15, 20 °C-T20, 25 °C-T25) for 30 days. Liver tissues were harvested at the end of the study for transcriptomic and metabolomic assessments. The T. rubripes larvae in the T15 group showed a significant decrease in total length and body weight compared to the T20 and T25 groups (p < 0.05). 1344, 416, and 2080 differentially expressed genes (DEGs) were identified in T15-vs-T20, T20-vs-T25, and T15-vs-T25 comparisons, respectively. Those DEGs were mainly enriched in metabolic, protein digestion and absorption, steroid biosynthesis, and glycerophospholipid metabolism pathways. 15 DEGs were randomly selected for RNA-seq validation, and the transcriptome results were consistent with the qPCR validation results, illustrating the accuracy of transcriptome sequencing. 340, 238, and 330 significantly different metabolites (SDMs) were identified in positive modes when comparing in T15-vs-T20, T20-vs-T25, and T15-vs-T25, respectively. Additionally, 145, 137, and 159 SDMs were identified in negative modes within the three comparisons. Those SDMs enriched in biosynthesis of secondary metabolites, glycerophospholipid metabolism, linoleic acid metabolism, and metabolic pathways. The integration of transcriptomic and metabolomic analyses indicated that DEGs and SDMs mainly enriched in metabolic pathways. These discoveries provide valuable insights into the effects of temperature on fish larvae in aquaculture, laying a foundation for future breeding approaches aimed at improving the growth of T. rubripes.PMID:39644865 | DOI:10.1016/j.cbd.2024.101371

J Chromatogr B Analyt Technol Biomed Life Sci. 2024 Dec 2;1251:124373. doi: 10.1016/j.jchromb.2024.124373. Online ahead of print.ABSTRACTBACKGROUND: Xuemaitong Capsule (XMT) is a widely recognized traditional Miao medicine extensively utilized in Chinese clinical settings. Previous studies have demonstrated XMT protective effects against acute myocardial ischemia (AMI). However, the mechanism by which XMT provides protection to AMI rats is yet to be fully understood.AIM OF THE STUDY: The purpose of this study was to investigate the protective mechanism of XMT on AMI rats through network pharmacology, traditional pharmacodynamics and metabolomics.MATERIAL AND METHODS: The components and potential targets of XMT were identified through the application of traditional Chinese medicine system pharmacology and traditional Chinese medicine molecular mechanism bioinformatics analysis tools. We constructed herb-composition-target networks and analyzed protein-protein interaction (PPI) networks. The potential mechanism was explored by pathway enrichment analysis. Subsequently, the AMI model was constructed by ligation of the anterior descending branch of the left coronary artery, and XMT protective effects on AMI rats were evaluated by analyzing the myocardial enzyme profiles, electrocardiograms(ECG), Triphenyltetrazolium chloride(TTC) staining, and Hematoxylin-Eosin (HE) staining in AMI rats. Metabolomics based on UHPLC-Q-Exactive Orbitrap MS was used to observe the protective effect of XMT on the serum metabolic profile of AMI, and multivariate statistical analysis further revealed the differential patterns of metabolites after XMT treatment. Finally, integrated pathway analysis was carried out to reveal the biological metabolic mechanism.RESULTS: A total of 392 active components of XMT acted with 624 targets for treating AMI. Pathway enrichment analysis revealed that XMT could treat AMI through TNF, MAPK and PI3K-Akt signaling pathways. Further, XMT could effectively prevent ST-segment elevation in the ECG, reduce the size of myocardial infarction, decrease cardiac weight index and cardiac enzyme levels, and mitigate histological damage in the hearts of AMI rats. In addition, XMT callback 117 metabolites and four metabolic pathways, including taurine and hypotaurine metabolism, phenylalanine metabolism, pyrimidine metabolism and retinol metabolism. Through integrating network pharmacology and metabolomics, we explored the biological mechanism by which XMT treats AMI. It was speculated that the mechanism of XMT is to regulate TNF signaling, PI3K-Akt pathway and MAPK signaling pathway, and participate in cell apoptosis, oxidative stress, immune and inflammatory reaction and other biological processes.CONCLUSION: XMT plays a protective role in AMI rats by regulating multiple metabolic biomarkers, multiple targets and pathways. Therefore, XMT may provide a potential strategy for the treatment of AMI.PMID:39644825 | DOI:10.1016/j.jchromb.2024.124373

EBioMedicine. 2024 Dec 6;111:105482. doi: 10.1016/j.ebiom.2024.105482. Online ahead of print.ABSTRACTBACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is associated with impaired regenerative capacity and poor postoperative prognosis following hepatectomy. Previous research has highlighted the importance of the gut-liver axis in the physiological and pathological processes of the liver. However, the contribution of gut bacteria to the regeneration of livers with MAFLD and its metabolic regulatory mechanisms remain elusive.METHODS: Partial hepatectomy (PHx) was performed on C57Bl/6J mice fed with high-fat diet (HFD) for 12 weeks. Pathological examination, immunohistochemistry, and qRT-PCR analysis were performed to assess the severity of steatosis and proliferative potential. The gut microbiome was examined by 16S rRNA gene sequencing and shotgun metagenomics, whereas liver metabolomics was analysed via untargeted and targeted metabolomics using liquid chromatography-tandem mass spectrometry (LC-MS).FINDINGS: HFD-induced hepatic steatosis in mice led to impaired liver regeneration following PHx. The gut microbiota and liver metabolites were altered along with the liver regeneration process. Longitudinal time-series analysis revealed dynamic alterations in these data, whereas correlation analysis screened out bacterial candidates that potentially influence liver regeneration in MAFLD by modulating metabolic pathways. Among these bacteria, the dominant bacterium Akkermansia was selected for subsequent investigation. MAFLD mice gavaged with Akkermansia muciniphila (A. muciniphila) exhibited reduced liver lipid accumulation and accelerated liver regeneration, possibly through the regulation of the tricarboxylic acid (TCA) cycle.INTERPRETATION: These data demonstrated the interplay between the gut microbiome, liver metabolomics, and liver regeneration in mice with MAFLD. A. muciniphila has the potential to serve as a clinical intervention agent to accelerate postoperative recovery in MAFLD.FUNDING: This work was supported by the Research Project of Jinan Microecological Biomedicine Shandong Laboratory [JNL-2022008B]; the Zhejiang Provincial Natural Science Foundation of China [LZ21H180001]; the Fundamental Research Funds for the Central Universities [No. 2022ZFJH003].PMID:39644773 | DOI:10.1016/j.ebiom.2024.105482

EBioMedicine. 2024 Dec 6;111:105484. doi: 10.1016/j.ebiom.2024.105484. Online ahead of print.ABSTRACTBACKGROUND: Sudden Infant Death Syndrome (SIDS) is a leading cause of postneonatal mortality. The absence of specific biomarkers of SIDS diagnosis and risk leaves a significant gap in understanding SIDS pathophysiology. Metabolomics offers an avenue to better understand SIDS biology and identifying potential biomarkers.METHODS: Using Metabolon Inc., global discovery panel, we analysed 828 metabolites from post-mortem serum samples of infants from the Chicago Infant Mortality Study (CIMS) and the NIH NeuroBioBank (NBB). In total, 300 infants (195 SIDS; 105 non-SIDS) across multiple race/ethnicities (70% Black, 13% White, and 16% Hispanic) were included. Metabolite associations with SIDS were performed using Welch's t-tests, linear and logistic regression, and network-cluster analyses.FINDINGS: We identified thirty-five significant metabolite predictors of SIDS after adjustment for age, sex, race and ethnicity, and post-mortem interval, including ornithine (OR 21.98; p-value 6.44e-7), 5-hydroxylysine (OR 19.48; p-value 6.78e-7), 1-stearoyl-2-linoleoyl-GPC (18:0/18:2) (OR 16.80; p-value 3.4e-7), ribitol (OR 8.19; p-value 4.2e-8), and arabitol/xylitol. Using Weighted Gene Co-expression Network Analysis (WGCNA), ten metabolite clusters were identified. Four exhibited significant associations with SIDS. The two most correlated clusters were enriched for metabolites in the tyrosine metabolism pathway and lipid (sphingomyelins) pathways.INTERPRETATION: We identified metabolite biomarkers within key biological pathways and processes (e.g., nitrogen metabolism, lipid and fatty acid metabolism, stress response, nerve cell communication, hormone regulation, oxidative stress) with potential implications in SIDS pathology. Further research is needed to validate these biomarkers in additional SIDS cohorts.FUNDING: The Chicago Infant Mortality Study was funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute on Deafness and Other Communication Disorders under contract number NO1-HD-3-3188, the Centers for Disease Control and Prevention and the Association of Teachers of Preventive Medicine under cooperative agreement number U50/CCU300860-06, and the Playmates in Heaven Foundation. The current analyses were funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development under 5R01HD101518-04.PMID:39644771 | DOI:10.1016/j.ebiom.2024.105484

J Chromatogr A. 2024 Dec 3;1740:465580. doi: 10.1016/j.chroma.2024.465580. Online ahead of print.ABSTRACTMetabolomics based on hydrophilic interaction liquid chromatography (HILIC) coupled with mass spectrometry (MS) is a powerful tool for polar metabolite identification and quantification to further contribute to biomarker discovery and disease mechanism elucidation. However, matrix effect (ME), which may lead to altered ionization efficiency due to co-eluting compounds, is a significant challenge during biological analysis. Therefore, ME evaluation plays a crucial role during method development. Two approaches to evaluate ME are using stable isotope labelled-internal standards (SIL-IS) and post-column infusion (PCI) of standards. In this study, we developed an untargeted HILIC-MS method by applying four PCI standards for ME evaluation. We found PCI is a compelling approach for ME assessment compared to SIL-IS method due to its advantage in untargeted analysis. Through the ME evaluation and chromatographic performance comparison of 18 SIL standards across three columns and three different mobile phase pH conditions, our findings revealed that the BEH-Z-HILIC column operated at pH 4 with 10 mM ammonium formate exhibited minimal ME and superior performance. The method showed exceptional linearity (R² > 0.98), reliable repeatability (RSD < 15 %), good inter-day precision (RSD < 30 %), and acceptable recovery (>75 %) for all SIL standards. Absolute matrix effect (AME) and relative matrix effect (RME) assessment in three plasma donors revealed a high consistency between PCI and SIL-IS approaches. Finally, this method coupled with the PCI approach was applied to 40 plasma samples. Fifty endogenous compounds were detected and their AME and RME were evaluated. Results showed that many compounds experienced severe ion suppression, though their ME variation between 40 samples is low. In conclusion, PCI method is a robust alternative for monitoring ME and evaluating ME of endogenous compounds during untargeted method optimization and biological analysis.PMID:39644743 | DOI:10.1016/j.chroma.2024.465580

Plant Physiol Biochem. 2024 Dec 3;219:109373. doi: 10.1016/j.plaphy.2024.109373. Online ahead of print.ABSTRACTThe mutants resistant to ethylene are helpful in deciphering the role of ethylene in plant development. We isolated an ethylene-resistant tomato (Solanum lycopersicum) mutant by screening for acetylene-resistant (atr-1) seedlings. The atr-1 mutant displayed resistance to kinetin, suggesting attenuation of the ethylene sensing response. atr-1 also exhibited resistance to ABA- and glucose-mediated inhibition of seed germination. Unlike the Never-ripe (Nr) mutant seedlings that were hypersensitive to glucose, atr-1 seedlings were resistant to glucose, indicating ethylene sensing in atr-1 is compromised in a manner distinct from Nr. Metabolically, atr-1 seedlings had lower levels of amino acids but higher levels of several phytohormones, including ABA. atr-1 plants grew faster and produced more flowers, leading to a higher fruit set. However, the atr-1 fruits took a longer duration to reach the red-ripe (RR) stage. The ripened atr-1 fruits retained high β-carotene and lycopene levels post-RR stage and had longer on-vine longevity. The metabolome profiles of post-RR stage atr-1 fruits revealed increased levels of sugars. The atr-1 had a P279L mutation in the GAF domain of the ETR4, a key ethylene receptor regulating tomato ripening. The atr-1 exhibits phenotypic traits distinct from the Sletr4-1 (G154S) mutant, thus represents a new ETR4 allele named Sletr4-2. Our study highlights that novel alleles in ethylene receptors may aid in enhancing the nutritional quality of tomato.PMID:39644684 | DOI:10.1016/j.plaphy.2024.109373

J Pharm Biomed Anal. 2024 Nov 28;255:116588. doi: 10.1016/j.jpba.2024.116588. Online ahead of print.ABSTRACTArtemisia species have been regarded as an important source of ethnic medicinal plants, such as A. annua and A. capillaris, both of which are widely used in clinical treatment. The clinical efficacy of A. japonica is similar to that of A. capillaris, but fewer pharmaceutical studies have been reported. Given that the extracts of A. japonica were observed to reduce the rectal temperature of febrile rats induced by LPS, this study was designed to demonstrate this regulatory effect of the extracts, with a particular focus on the lipidomic profiling of the febrile rat hypothalamus. A total of 72 differential metabolites were filtered out and the association between lipid profiling and potential mechanism was explored. Sphingolipid, glycerophospholipid, arachidonic acid and ether lipid metabolism pathways were significantly enriched. TNF-α, IL-6 and PGE2 cytokines in the hypothalamus were significantly downregulated by the intervention of the extracts of A. japonica. Enzymatic reaction enrichment analysis suggested that PEMT and COX-2 might be potential targets of the efficacy, and which were testified to be downregulated by the ELISA assay under the extracts intervention.PMID:39644683 | DOI:10.1016/j.jpba.2024.116588

J Pharm Biomed Anal. 2024 Nov 22;255:116575. doi: 10.1016/j.jpba.2024.116575. Online ahead of print.ABSTRACTArtificial sweeteners (ASs) and dyes are widely used in foods, beverages and pharmaceutical and are recognized as emerging environmental contaminants due to their persistence and widespread occurrence. These substances often pass through the human body unchanged and resist wastewater treatment processes, leading to continuous introduction into aquatic environments and potential long-lasting term environmental effects. This study investigated, for the first time, the biodegradability of nine commercial dietary supplements, both natural and those containing ASs and synthetic dyes, using the Organisation for Economic Cooperation and Development (OECD) 301 F ready biodegradation test (RBT), which is a respirometry-manometric method. While the products showed good biodegradability, those containing ASs and dyes were further studied to determine their fate at the end of the RBT. The study involved developing and validating a chromatographic method to quantitatively determine the presence of Acesulfame K (1), Sucralose (2), Tartrazine (3) and Carmoisine (4) in the RBT mineral medium, using ultra-high performance liquid chromatography (UHPLC) coupled with two detectors: a high-resolution mass-spectrometer with quadrupole time-of-flight (qToF) and a UV-Vis diode array detector (DAD). Results indicated that these additives were not readily biodegraded, highlighting a potential significant environmental concern. This issue extends beyond dietary supplements to all Pharmaceutical and Personal Care Products (PPCP) including drugs and medical devices. The findings underscore the importance of raising cultural awareness about the environmental impact of persistent substances, encouraging the healthcare chain and patients to make informed choices. From a One Health perspective, reducing environmental contamination can lead to positive outcomes for human health.PMID:39644680 | DOI:10.1016/j.jpba.2024.116575

J Trace Elem Med Biol. 2024 Dec 6;87:127579. doi: 10.1016/j.jtemb.2024.127579. Online ahead of print.NO ABSTRACTPMID:39644677 | DOI:10.1016/j.jtemb.2024.127579

Food Chem. 2024 Dec 2;467:142323. doi: 10.1016/j.foodchem.2024.142323. Online ahead of print.ABSTRACTEdible fungal fruiting bodies develop from mycelia that experienced physiological knotting, establishing a tight nutrient connection between mycelia and fruiting bodies. Despite this connection, limited research has explored this field. This study aimed to elucidate the crude polysaccharide and protein contents in mycelia and fruiting bodies of 5 main edible fungi cultivars: Flammulina velutipes, Hypsizygus marmoreus, Lyophyllum decastes etc., under defined nutrient conditions. H. marmoreus was selected as an example, the study investigated nutrient relationships in both mycelia and fruiting bodies across 5 media with varying carbon to nitrogen ratios (C/N). Results indicated higher crude polysaccharide and protein contents in mycelia compared to fruiting bodies. A predictive model for the crude polysaccharide and protein contents of H. marmoreus fruiting bodies was developed using partial least squares (PLS) method. Predicted values closely matched experimental determinations, providing the model's accuracy. The impact of different C/N on crude fiber content in the culture media was minimal. Metabolomics analysis of H. marmoreus revealed significant up-regulation of carbohydrate metabolites (72 %) and amino acid metabolites (84 %) in mycelia relative to fruiting bodies. Specifically, metabolites involved in polysaccharide precursor synthesis pathways (Gal1P, Glc-1P, UDP-Glc) and protein precursor synthesis pathways (9 amino acids) showed heightened levels in mycelia, which suggested a possible reason for the observed higher crude polysaccharide and protein content in mycelia compared to fruiting bodies. Overall, these results provide a crucial theoretical foundation for predicting and enhancing edible fungal quality and diversity through mycelial studies. They also establish a cornerstone for accelerating new variety development and optimizing high-quality mushroom production formulations.PMID:39644664 | DOI:10.1016/j.foodchem.2024.142323

Food Chem. 2024 Dec 4;467:142344. doi: 10.1016/j.foodchem.2024.142344. Online ahead of print.ABSTRACTChicory, recognized as a functional food, is increasingly becoming the focus of research. This study aimed to investigate the in vitro impact of gastrointestinal digestion on the composition and bioactive properties of chicory decoction. Chicory flour, derived from the roots, was transformed into an aqueous decoction and was subjected to simulated in vitro human gastrointestinal digestion (SGID). For the first time, the influence of the digestive process on specific classes of bioactive molecules was tracked across different digestive compartments (oral, gastric, and intestinal) using a metabolomic approach. Concurrently, the antioxidant, anti-inflammatory, and intestinal hormone regulation effects were assessed before and after SGID. The findings revealed that specific transformations of chlorogenic acid (CGA) and sesquiterpene lactones (STL) during SGID enhanced antioxidant and anti-inflammatory properties post-digestion. Quantitative results demonstrated a significant increase in ROS scavenging capacity and metabolite activity.PMID:39644662 | DOI:10.1016/j.foodchem.2024.142344

Atherosclerosis. 2024 Dec 6;401:119071. doi: 10.1016/j.atherosclerosis.2024.119071. Online ahead of print.NO ABSTRACTPMID:39644614 | DOI:10.1016/j.atherosclerosis.2024.119071

STAR Protoc. 2024 Dec 6;5(4):103478. doi: 10.1016/j.xpro.2024.103478. Online ahead of print.ABSTRACT2-deoxy-D-glucose (2DG) is a glucose analog converted to 2-deoxy-D-glucose-6-phosphate (2DG-6P) by hexokinase in glycolysis. While 2DG commonly measures glucose uptake, 2DG-6P detects glucose utilization. Here, we present a protocol to measure glucose utilization in various tissues after entering a mouse's body using radiolabeled 2DG. We describe steps for preparing mice and chemicals, extracting blood, adding chemicals, and dissolving tissue. We then detail procedures for calculating glucose utilization using the trapezoid rule.PMID:39644497 | DOI:10.1016/j.xpro.2024.103478

Med Oncol. 2024 Dec 7;42(1):23. doi: 10.1007/s12032-024-02575-3.ABSTRACTDespite significant advancements in the research of the pathogenesis mechanisms of Myelodysplastic Neoplasm (MDS) in recent years, there are still many gaps to fill. The advancement of metabolomics studies has led to a research booming in clarifying the impact of metabolic abnormalities during the pathogenesis of MDS. The present review primarily focuses on the dysregulated metabolic pathways, exploring the influences on the pathogenesis of MDS and their roles during the course of the disease. Furthermore, we discuss the potential of relevant metabolic pathways as therapeutic targets, along with the latest metabolic-related treatment drugs and approaches.PMID:39644425 | DOI:10.1007/s12032-024-02575-3

Planta. 2024 Dec 6;261(1):8. doi: 10.1007/s00425-024-04585-x.ABSTRACTNutrient deficiency intensifies drought and salinity stress on rice growth. Bacillus amyloliquefaciens inoculation provides resilience through modulation in metabolic and gene regulation to enhance growth, nutrient uptake, and stress tolerance. Soil nutrient deficiencies amplify the detrimental effects of abiotic stresses, such as drought and salinity, creating substantial challenges for overall plant health and crop productivity. Traditional methods for developing stress-resistant varieties are often slow and labor-intensive. Previously, we demonstrated that plant growth-promoting rhizobacteria Bacillus amyloliquefaciens strain SN13 effectively alleviates stress induced by sub-optimum nutrient conditions in rice. In this study, we evaluated the effectiveness of SN13 in reducing the compounded impacts of drought and salinity under varying nutrient regimes in rice seedlings. The results demonstrated that PGPR inoculation not only improved the growth parameters, nutrient content, and physio-biochemical characteristics under nutrient-limited conditions, but also reduced the oxidative stress markers. The altered expression of stress-related and transcription factor genes (USP, DEF, CYP450, GST, MYB, and bZIP) revealed the regulatory effect of PGPR in enhancing stress tolerance through these genes. GC-MS-based untargeted metabolomic analysis revealed that PGPR significantly influenced various metabolic pathways, including galactose metabolism, fructose and mannose metabolism, and fatty acid biosynthesis pathways, suggesting that PGPR affects both energy production and stress-protective mechanisms, facilitating better growth and survival of rice seedlings.PMID:39643822 | DOI:10.1007/s00425-024-04585-x

Biogerontology. 2024 Dec 6;26(1):21. doi: 10.1007/s10522-024-10166-y.ABSTRACTNew insights into the metabolic mechanisms of frailty are needed. This study aimed to identify serum metabolites linked to frailty phenotype and its component through gas chromatography-mass spectrometry metabolomic analysis among community-dwelling older individuals. An exploratory, cross-sectional case-control study. Setting and participants: The participants were recruited from the ''Otassha Study,'' a cohort study conducted in Itabashi Ward, Tokyo, targeting women aged 65 years and older. The study population included 39 frail and 76 robust individuals. Metabolomic analysis was performed using the GCMS-TQTM8040 NX system and the Smart Metabolites Database Ver.2 to explore the primary metabolite characteristic of a frailty state. Conditional logistic regression analysis was conducted with frailty as the outcome and with metabolites as exposures. Concentrations of seven metabolites, including caffeine, catechol, paraxanthine, niacinamide, 5-hydroxymethyl-2-furoic acid, daidzein, and cytosine were lower in the frail than in the robust individuals. Odds ratios [95% confidence intervals] for frailty by halving the value were significant for catechol (1.26 [1.00, 1.59]), 5-hydroxymethyl-2-furoic acid (1.28 [1.04, 1.58]), caffeine (1.37 [1.07, 1.75]), paraxanthine (1.18 [1.00, 1.39]), and daidzein (1.29 [1.02, 1.62]). Furthermore, distinct patterns of metabolites associated with specific frailty symptoms, such as muscle weakness, fatigue, and reduced physical activity, were identified, especially with 5-hydroxymethyl-2-furoic acid and caffeine commonly associated with these components. Metabolomic analysis identified metabolites associated with frailty. In particular, low levels of caffeine, catechol, paraxanthine, niacinamide, 5-hydroxymethyl-2-furoate, daidzein, and cytosine contributed to frailty. These results provide new insights into the pathophysiology of frailty through metabolomic analysis.PMID:39643817 | DOI:10.1007/s10522-024-10166-y

Plant Cell Rep. 2024 Dec 7;44(1):1. doi: 10.1007/s00299-024-03393-7.ABSTRACTMulti-omics studies have shown that strigolactone modulates phenolic acid accumulation in the leaves of R. chrysanthum and can enable it to cope with UV-B stress. UV-B stress is an abiotic stress that plants will inevitably suffer during growth and can seriously affect the normal physiological state of plants. Strigolactone, a phytohormone, has been less studied and it is important to investigate its regulation of plant growth under UV-B radiation. In the present study, we investigated the changes in leaves of Rhododendron chrysanthum Pall. (R. chrysanthum) under UV-B radiation. The leaves of R. chrysanthum were collected for widely targeted metabolomics, hormonomics, transcriptomics, proteomics and acetylated proteomics assays. The results showed that the leaves of R. chrysanthum were able to produce a large amount of differential phenolic acids with antioxidant effects under UV-B stress, the content of strigolactone was significantly elevated, and the genes and proteins involved in phenolic acid biosynthesis and strigolactone biosynthesis were significantly altered, and some of the proteins (ASP1, 4CLL7, and CCD1) underwent acetylation modification. Meanwhile, correlation analysis showed that strigolactone was strongly correlated with differential phenolic acids, which might regulate the adaptive responses of the R. chrysanthum under UV-B stress. In this paper, we investigated the effects of strigolactone on the accumulation of phenolic acid compounds and found a strong correlation between strigolactone and elevated phenolic acid levels, which provided insights into the molecular mechanism of plant regulation of phenolic acid accumulation, and facilitated the adoption of measures to mitigate the adverse effects of UV-B stress on plant growth, and to achieve the purpose of protecting plant germplasm resources.PMID:39643793 | DOI:10.1007/s00299-024-03393-7

J Antibiot (Tokyo). 2024 Dec 6. doi: 10.1038/s41429-024-00792-6. Online ahead of print.ABSTRACTChemical and biological stimulus screening in a hypogean actinomycete was used to elicit secondary metabolism. Optimal biosynthesis of bioactive natural products was identified using Multiplexed Activity Profiling for determining dose-dependent activity via six single-cell biological readouts. Bioactive extracts were fractioned to establish candidate compounds for isolation using Multiplexed Activity Metabolomics by correlating microtiter well-isolated phenotypes and extracted ion current peaks. This guided the isolation of four filipin polyene macrolides including a new metabolite filipin XV, an alkyl side-chain hydroxylated congener of the filipin chainin, with substantially attenuated cytotoxicity. Filipin-specific cytotoxicity was confirmed using flow cytometry and fluorescence microscopy.PMID:39643649 | DOI:10.1038/s41429-024-00792-6

J Expo Sci Environ Epidemiol. 2024 Dec 6. doi: 10.1038/s41370-024-00736-0. Online ahead of print.ABSTRACTBACKGROUND: The chemical exposome includes exposure to numerous environmental and endogenous molecules, many of which have been linked to reproductive outcomes due to their endocrine-disrupting properties. As several breast cancer risk factors, including age and parity, are related to reproduction, it is imperative to investigate the interplay between such factors and the chemical exposome prior to conducting large scale exposome-based breast cancer studies.OBJECTIVE: This pilot study aimed to provide an overview of the chemical exposome in plasma samples from healthy women and identify associations between environmental exposures and three risk factors for breast cancer: age, parity, and age at menarche.MATERIAL AND METHODS: Plasma samples (n = 161), were selected based on reproductive history from 100 women participating in the Northern Sweden Health and Disease Study, between 1987 and 2006. Samples were analyzed by liquid chromatography high-resolution mass spectrometry (LC-HRMS) for 77 priority target analytes including contaminants and hormones, with simultaneous untargeted profiling of the chemical exposome and metabolome. Linear mixed effects models were applied to test associations between risk factors and chemical levels.RESULTS: Fifty-five target analytes were detected in at least one individual and over 94,000 untargeted features were detected across all samples. Among untargeted features, 430 could be annotated and were broadly classified as environmental (246), endogenous (167) or ambiguous (17). Applying mixed effect models to features detected in at least 70% of the samples (16,778), we found seven targeted analytes (including caffeine and various per- and poly-fluoroalkyl substances) and 38 untargeted features, positively associated with age. The directionality of these associations reversed for parity, decreasing with increasing births. Seven separate targeted analytes were associated with age at menarche.SIGNIFICANCE: This study demonstrates how a comprehensive chemical exposome approach can be used to inform future research prioritization regarding associations between known and unknown substances, reproduction, and breast cancer risk.IMPACT STATEMENT: This study illustrates how chemical exposomics of long-term stored blood samples offers valuable insights to discover chemical exposures and their potential links to disease in humans, particularly those related to reproduction and breast cancer risk factors.PMID:39643621 | DOI:10.1038/s41370-024-00736-0