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Pediatric Obesity Jul 2024This study identified metabolite modules associated with adiposity and body fat distribution in childhood using gold-standard measurements.
OBJECTIVE
This study identified metabolite modules associated with adiposity and body fat distribution in childhood using gold-standard measurements.
METHODS
We used cross-sectional data from 329 children at mid-childhood (age 5.3 ± 0.3 years; BMI 15.7 ± 1.5 kg/m) from the Genetics of Glucose regulation in Gestation and Growth (Gen3G), a prospective pre-birth cohort. We quantified 1038 plasma metabolites and measured body composition using the gold-standard dual-energy x-ray absorptiometry (DXA), in addition to skinfold, waist circumference, and BMI. We applied weighted-correlation network analysis to identify a network of highly correlated metabolite modules. Spearman's partial correlations were applied to determine the associations of adiposity with metabolite modules and individual metabolites with false discovery rate (FDR) correction.
RESULTS
We identified a 'green' module of 120 metabolites, primarily comprised of lipids (mostly sphingomyelins and phosphatidylcholine), that showed positive correlations (all FDR p < 0.05) with DXA estimates of total and truncal fat (ρ = 0.11-0.19), skinfold measures (ρ = 0.09-0.26), and BMI and waist circumference (ρ = 0.15 and 0.18, respectively). These correlations were similar when stratified by sex. Within this module, sphingomyelin (d18:2/14:0, d18:1/14:1)*, a sphingomyelin sub-specie that is an important component of cell membranes, showed the strongest associations.
CONCLUSIONS
A module of metabolites was associated with adiposity measures in childhood.
PubMed: 38958048
DOI: 10.1111/ijpo.13149 -
IScience Jun 2024Osteophyte formation, a key indicator of osteoarthritis (OA) severity, remains poorly understood in its relation to gut microbiota and metabolites in knee osteoarthritis...
Osteophyte formation, a key indicator of osteoarthritis (OA) severity, remains poorly understood in its relation to gut microbiota and metabolites in knee osteoarthritis (KOA). We conducted 16S rDNA sequencing and untargeted metabolomics on fecal and serum samples from 20 healthy volunteers, 80 KOA patients in Guangdong, and 100 in Inner Mongolia, respectively. Through bioinformatics analysis, we identified 3 genera and 5 serum metabolites associated with KOA osteophyte formation. Blautia abundance negatively correlated with meat, cheese, and bean consumption. The 5 serum metabolites negatively correlated with dairy, beef, cheese, sugar, and salt intake, yet positively with age and oil consumption. Higher Blautia levels in the gut may contribute to KOA osteophyte formation, with serum metabolites LTB4 and PGD2 potentially serving as biomarkers. KOA patients in Inner Mongolia exhibited lower Blautia levels and reduced expression of 5 serum metabolites, possibly due to cheese consumption habits, resulting in less osteophyte formation.
PubMed: 38957790
DOI: 10.1016/j.isci.2024.110111 -
Frontiers in Plant Science 2024Salt stress is a major environmental factor that constrains soybean growth, development, and productivity. Flavonoids are key secondary metabolites that play a crucial...
INTRODUCTION
Salt stress is a major environmental factor that constrains soybean growth, development, and productivity. Flavonoids are key secondary metabolites that play a crucial role in enhancing plant resistance to both biotic and abiotic stress. However, a comprehensive understanding of the regulatory mechanisms underlying flavonoid biosynthesis under salt stress in soybean is lacking.
METHODS
In this study, an integrative analysis of soybean metabolome and transcriptome was conducted using two soybean lines, FQ03 (salt-sensitive, SS) and FQ07 (salt-tolerant, ST).
RESULTS
A total of 650 significantly changed metabolites were identified in SS and ST after salt stress treatment. Among them, 151 flavonoids were categorized into nine classes, with flavones and flavonols being the predominant flavonoid types in soybean. Heatmap analysis showed higher contents of most flavonoid metabolites in ST than in SS under salt stress, and the total flavonoid content in ST was significantly higher than that in SS. In addition, transcriptome analysis revealed a higher number of differentially expressed genes (DEGs) in ST than in SS under salt stress. KEGG enrichment analysis revealed that DEGs were mainly enriched in pathways related to phenylpropanoid biosynthesis, isoflavonoid biosynthesis, flavonoid biosynthesis, as well as flavone and flavonol biosynthesis. Notably, 55 DEGs that were mapped to the flavonoid biosynthetic pathway were identified, with most showing higher expression levels in ST than in SS. Weighted gene correlation network analysis identified eight structural genes and six transcription factor genes as key regulators of flavonoid biosynthesis within the blue module. Furthermore, qRT-PCR results confirmed the accuracy of the transcriptomic data and reliability of the identified candidate genes.
DISCUSSION
This study provides insights into the regulatory mechanisms underlying salt stress responses in soybean and highlights hub genes as potential targets for developing salt-tolerant soybean varieties.
PubMed: 38957602
DOI: 10.3389/fpls.2024.1415867 -
Frontiers in Plant Science 2024is an important edible and medicinal plant. To gain a comprehensive and clear understanding of the variation patterns of metabolites in , we employed the UPLC-MS...
is an important edible and medicinal plant. To gain a comprehensive and clear understanding of the variation patterns of metabolites in , we employed the UPLC-MS platform along with widely targeted metabolomics techniques to analyze the metabolites in the stems and leaves of at different stages. Our results revealed a total of 1228 detected metabolites, including 241 phenolic acids, 203 flavonoids, 152 lipids, 128 terpenes, 106 amino acids, 79 organic acids, 74 saccharides, 66 alkaloids, 44 lignans, etc. As the growth time increased, the differential metabolites (DAMs) mainly enriched in leaves were terpenoids, phenolic acids, and lipids, while the DAMs primarily enriched in stems were terpenoids. Compared to stems, there were more differential flavonoids in leaves, and saccharides and flavonoids were significantly enriched in leaves during the S1 and S2 stages. Additionally, we identified 13, 10, and 23 potential markers in leaf, stem, and leaf vs. stem comparison groups. KEGG enrichment analysis revealed that arginine biosynthesis was the common differential metabolic pathway in different growth stages and tissues. Overall, this study comprehensively analyzed the metabolic profile information of , serving as a solid foundation for its further development and utilization.
PubMed: 38957601
DOI: 10.3389/fpls.2024.1378881 -
Frontiers in Plant Science 2024Tree nut consumption has been widely associated with various health benefits, with walnuts, in particular, being linked with improved cardiovascular and neurological...
Tree nut consumption has been widely associated with various health benefits, with walnuts, in particular, being linked with improved cardiovascular and neurological health. These benefits have been attributed to walnuts' vast array of phenolic antioxidants and abundant polyunsaturated fatty acids. However, recent studies have revealed unexpected clinical outcomes related to walnut consumption, which cannot be explained simply with the aforementioned molecular hallmarks. With the goal of discovering potential molecular sources of these unexplained clinical outcomes, an exploratory untargeted metabolomics analysis of the isolated walnut pellicle was conducted. This analysis revealed a myriad of unusual lipids, including oxylipins and endocannabinoids. These lipid classes, which are likely present in the pellicle to enhance the seeds' defenses due to their antimicrobial properties, also have known potent bioactivities as mammalian signaling molecules and homeostatic regulators. Given the potential value of this tissue for human health, with respect to its "bioactive" lipid fraction, we sought to quantify the amounts of these compounds in pellicle-enriched waste by-products of mechanized walnut processing in California. An impressive repertoire of these compounds was revealed in these matrices, and in notably significant concentrations. This discovery establishes these low-value agriculture wastes promising candidates for valorization and translation into high-value, health-promoting products; as these molecules represent a potential explanation for the unexpected clinical outcomes of walnut consumption. This "hidden quality" of the walnut pellicle may encourage further consumption of walnuts, and walnut industries may benefit from a revaluation of abundant pellicle-enriched waste streams, leading to increased sustainability and profitability through waste upcycling.
PubMed: 38957599
DOI: 10.3389/fpls.2024.1395543 -
Drug Design, Development and Therapy 2024To explored the potential molecular mechanism of Sugemule-4 decoction (MMS-4D) in treating insomnia.
Integration of Gut Microbiota, Serum Metabolomic, and Network Pharmacology to Reveal the Anti Insomnia Mechanism of Mongolian Medicine Sugemule-4 Decoction on Insomnia Model Rats.
OBJECTIVE
To explored the potential molecular mechanism of Sugemule-4 decoction (MMS-4D) in treating insomnia.
METHODS
-4-chlorophenylalanine (PCPA) + chronic unpredictable mild stress stimulation (CUMS) was used to induce an insomnia model in rats. After the model was successfully established, MMS-4D was intervened at low, medium, and high doses for 7 days. The open-field test (OFT) was used to preliminarily evaluate the efficacy. The potential mechanism of MMS-4D in treating insomnia was investigated using gut microbiota, serum metabolomics, and network pharmacology (NP). Experimental validation of the main components of the key pathways was carried out using ELISA and Western blot.
RESULTS
The weights of the insomnia-model rats were significantly raised ( ≤ 0.05), the total exercise distance in the OFT increased ( ≤ 0.05), the rest time shortened, and the number of standing times increased ( ≤ 0.05), after treatment with MMS-4D. Moreover, there was a substantial recovery in the 5-HT, DA, GABA, and Glu levels in the hypothalamus tissue and the 5-HT and GABA levels in the colon tissue of rats. The expression of DAT and DRD1 proteins in the hippocampus of insomnia rats reduced after drug treatment. MMS-4D may treat insomnia by regulating different crucial pathways including 5-HT -, DA -, GABA -, and Glu-mediated neuroactive light receiver interaction, cAMP signaling pathway, serotonergic, glutamatergic, dopaminergic, and GABAergic synapses.
CONCLUSION
This study revealed that MMS-4D can improve the general state and behavioral changes of insomnia model rats. Its mechanism may be related to the reversal of abnormal pathways mediated by 5-HT, DA, GABA, and Glu, such as Serotonergic synapse, Dopaminergic synapse, Glutamatergic synapse, and GABAergic synapse.
Topics: Animals; Rats; Sleep Initiation and Maintenance Disorders; Network Pharmacology; Gastrointestinal Microbiome; Male; Disease Models, Animal; Rats, Sprague-Dawley; Drugs, Chinese Herbal; Metabolomics; Dose-Response Relationship, Drug
PubMed: 38957410
DOI: 10.2147/DDDT.S455600 -
Journal of Agricultural and Food... Jul 2024Aflatoxin B (AFB), a mycotoxin and natural carcinogen, commonly contaminates cereals and animal feeds, posing serious health risks to human and animal. In this study,...
Aflatoxin B (AFB), a mycotoxin and natural carcinogen, commonly contaminates cereals and animal feeds, posing serious health risks to human and animal. In this study, ZG08 isolated from kimchi could effectively remove 80.93% of AFB within 72 h at 37 °C and pH 7.0. Metabolome and transcriptome analysis showed that metabolic processes including glycerophospholipid metabolism and amino acid metabolism were most affected in ZG08 exposed to AFB. The adaptation mechanism likely involved activation of the thioredoxin system to restore intracellular redox equilibrium. The key genes, and , overexpressed in BL21, achieved degradation rates of 60.15% and 47.16% for 100 μg/kg AFB under optimal conditions of 37 °C and pH 8.0 and 45 °C and pH 7.0, respectively. The degradation products, identified as AFD, were less cytotoxic than AFB in HepG2 cells. These findings suggest potential strategies for utilizing probiotics and engineered enzymes in AFB detoxification.
PubMed: 38957116
DOI: 10.1021/acs.jafc.4c04055 -
Cancer Research Communications Jul 2024Various lines of investigation support a signaling interphase shared by receptor tyrosine kinases and the DNA damage response. However, the underlying network nodes and...
Various lines of investigation support a signaling interphase shared by receptor tyrosine kinases and the DNA damage response. However, the underlying network nodes and their contribution to the maintenance of DNA integrity remain unknown. We explored MET-related metabolic pathways whose interruption compromises proper resolution of DNA damage. Discovery metabolomics combined with transcriptomics identified changes in pathways relevant to DNA repair following MET inhibition (METi). METi by tepotinib was associated with formation of γH2AX foci and with significant alterations in major metabolic circuits such as glycolysis, gluconeogenesis, and purine, pyrimidine, amino acids, and lipids metabolism. 5'-Phosphoribosyl-N-formylglycinamide (FGAR), a de novo purine synthesis pathway metabolite, was consistently decreased in in vitro and in vivo MET-dependent models, and a METi-related depletion of dNTPs was observed. METi instigated the downregulation of critical purine synthesis enzymes including phosphoribosylglycinamide formyltransferase (GART) which catalyzes FGAR synthesis. Genes encoding these enzymes are regulated through E2F1, whose levels decrease upon METi in MET-driven cells and xenografts. Transient E2F1 overexpression prevented dNTPs depletion and the concomitant METi-associated DNA damage in MET-driven cells. We conclude that DNA damage following METi results from dNTPs reduction via downregulation of E2F1 and a consequent decline of de novo purine synthesis.
PubMed: 38957115
DOI: 10.1158/2767-9764.CRC-23-0370 -
Chinese Medicine Jul 2024Irinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from...
BACKGROUND
Irinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from Huangqin Decoction (HQD) have been proven to enhance the anticancer activity of CPT-11 in our previous study.
OBJECTIVE
This study aimed to determine the optimal combination of the four components for sensitizing CPT-11 as well as to explore the underlying mechanism.
METHODS
The orthogonal design method was applied to obtain candidate combinations (Cmb1-9) of the four components. The influence of different combinations on the anticancer effect of CPT-11 was first evaluated in vitro by cell viability, wound healing ability, cloning formation, apoptosis, and cell cycle arrest. Then, a CRC xenograft mice model was constructed to evaluate the anticancer effect of the optimal combination in vivo. Potential mechanisms of the optimal combination exerting a sensitization effect combined with CPT-11 against CRC were analyzed by targeted metabolomics.
RESULTS
In vitro experiments determined that Cmb8 comprised of baicalin, baicalein, wogonin, and glycyrrhizic acid at the concentrations of 17 μM, 47 μM, 46.5 μM and 9.8 μM respectively was the most effective combination. Importantly, the cell viability assay showed that Cmb8 exhibited synergistic anticancer activity in combination with CPT-11. In in vivo experiments, this combination (15 mg/kg of baicalin, 24 mg/kg of baicalein, 24 mg/kg of wogonin, and 15 mg/kg of glycyrrhizic acid) also showed a synergistic anticancer effect. Meanwhile, inflammatory factors and pathological examination of the colon showed that Cmb8 could alleviate the gastrointestinal damage induced by CPT-11. Metabolic profiling of the tumors suggested that the synergistic anticancer effect of Cmb8 might be related to the regulation of fatty acid metabolism.
CONCLUSION
The optimal combination of four components derived from HQD for the synergistic sensitization of CPT-11 against CRC was identified.
PubMed: 38956673
DOI: 10.1186/s13020-024-00967-1 -
Journal of Nanobiotechnology Jul 2024Nanotechnology holds revolutionary potential in the field of agriculture, with zinc oxide nanoparticles (ZnO NPs) demonstrating advantages in promoting crop growth....
BACKGROUND
Nanotechnology holds revolutionary potential in the field of agriculture, with zinc oxide nanoparticles (ZnO NPs) demonstrating advantages in promoting crop growth. Enhanced photosynthetic efficiency is closely linked to improved vigor and superior quality in tea plants, complemented by the beneficial role of phyllosphere microorganisms in maintaining plant health. However, the effects of ZnO NPs on the photosynthesis of tea plants, the sprouting of new shoots, and the community of phyllosphere microorganisms have not been fully investigated.
RESULTS
This study investigated the photosynthetic physiological parameters of tea plants under the influence of ZnO NPs, the content of key photosynthetic enzymes such as RubisCO, chlorophyll content, chlorophyll fluorescence parameters, transcriptomic and extensive targeted metabolomic profiles of leaves and new shoots, mineral element composition in these tissues, and the epiphytic and endophytic microbial communities within the phyllosphere. The results indicated that ZnO NPs could enhance the photosynthesis of tea plants, upregulate the expression of some genes related to photosynthesis, increase the accumulation of photosynthetic products, promote the development of new shoots, and alter the content of various mineral elements in the leaves and new shoots of tea plants. Furthermore, the application of ZnO NPs was observed to favorably influence the microbial community structure within the phyllosphere of tea plants. This shift in microbial community dynamics suggests a potential for ZnO NPs to contribute to plant health and productivity by modulating the phyllosphere microbiome.
CONCLUSION
This study demonstrates that ZnO NPs have a positive impact on the photosynthesis of tea plants, the sprouting of new shoots, and the community of phyllosphere microorganisms, which can improve the growth condition of tea plants. These findings provide new scientific evidence for the application of ZnO NPs in sustainable agricultural development and contribute to advancing research in nanobiotechnology aimed at enhancing crop yield and quality.
Topics: Zinc Oxide; Photosynthesis; Camellia sinensis; Plant Shoots; Microbiota; Plant Leaves; Metal Nanoparticles; Chlorophyll; Nanoparticles
PubMed: 38956645
DOI: 10.1186/s12951-024-02667-2