Metabolites最新文献

Female infertility is a complex and multifaceted condition that affects millions of women globally [...].

Background/objectives: Fibroblast growth factor 21 (FGF21) is a hormonal regulator of lipid and glucose metabolism exerting protection against atherosclerosis by multiple actions on the blood vessels, liver, and adipose tissues. We aimed to investigate serum FGF21 level and its relation to thyroid hormones and metabolic parameters among patients with Hashimoto's thyroiditis (HT).

Methods: Eighty patients with HT on levothyroxine treatment and eighty-two age- and BMI-matched adults without thyroid disease serving as controls were enrolled. Serum FGF21 concentrations were determined with an enzyme-linked immunosorbent assay.

Results: Median serum FGF21 level was significantly lower in HT patients compared with controls (74.2 (33.4-148.3) pg/mL vs. 131.9 (44.8-236.3) pg/mL; p = 0.03). We found a positive correlation between FGF21 and age, triglyceride, total cholesterol, and low-density lipoprotein cholesterol in both groups, while thyroid stimulating hormone and C-reactive protein showed a positive correlation, and thyroxine had an inverse correlation with FGF21 only in control subjects. According to multiple regression analyses, thyroid status is the main predictor of FGF21 in healthy controls, while it is not a significant predictor of FGF21 among HT patients on levothyroxine supplementation therapy.

Conclusions: Our results indicate that the physiological role of thyroid function in the regulation of FGF21 synthesis is impaired in HT patients, which may contribute to the metabolic alterations characteristic of HT patients.

Background/Objectives:Meconopsis has long been used in traditional Tibetan medicine to treat various inflammatory and pain-related conditions. However, blue-flowered Meconopsis (M. betonicifolia) is becoming increasingly scarce due to overharvesting. As a potential alternative, yellow-flowered Meconopsis (M. integrifolia) shows promise but requires comprehensive characterization. This study aimed to evaluate and compare the anti-inflammatory potential of yellow- and blue-flowered Meconopsis species. Methods: Liquid chromatography-mass spectrometry (LC-MS) techniques were used to analyze the chemical profiles of yellow- and blue-flowered Meconopsis. Putative targets of shared constituents were subjected to GO and disease enrichment analysis. The LPS-induced RAW264.7 macrophage model was employed to assess anti-inflammatory effects. Metabolomics was applied to gain mechanistic insights. Results: LC-MS revealed over 70% chemical similarity between species. Enrichment analysis associated targets with inflammation-related pathways. In macrophage assays, both species demonstrated dose-dependent antioxidative and anti-inflammatory activities, with yellow Meconopsis exhibiting superior efficacy. Metabolomics showed modulation of key inflammatory metabolic pathways. Conclusions: This integrative study validated yellow-flowered Meconopsis as a credible alternative to its blue-flowered counterpart for anti-inflammatory applications. Metabolic profiling provided initial clues regarding their multi-targeted modes of action, highlighting their potential for sustainable utilization and biodiversity conservation.

Background/Objectives: Excessive reactive oxygen species (ROS) can lead to oxidative stress, which has become an urgent problem requiring effective solutions. Due to the drawbacks of chemically synthesized antioxidants, there is a growing interest in natural antioxidants, particularly antioxidant peptides. Methods: By reviewing recent literature on antioxidant peptides, particularly those extracted from various parts of fish, summarize which fish by-products are more conducive to the extraction of antioxidant peptides and elaborate on their characteristics. Results: This article summarizes recent advancements in extracting antioxidant peptides from fish processing by-products, Briefly introduced the purification and identification process of antioxidant peptides, specifically focusing on the extraction of antioxidant peptides from various fish by-products. Additionally, this article comprehensively reviews the relationship between amino acid residues that compose antioxidant peptides and their potential mechanisms of action. It explores the impact of amino acid types, molecular weight, and structure-activity relationships on antioxidant efficacy. Conclusions: Different amino acid residues can contribute to the antioxidant activity of peptides by scavenging free radicals, chelating metal ions, and modulating enzyme activities. The smaller the molecular weight of the antioxidant peptide, the stronger its antioxidant activity. Additionally, the antioxidant activity of peptides is influenced by specific amino acids located at the C-terminus and N-terminus positions. Simultaneously, this review provides a more systematic analysis and a broader perspective based on existing research, concluded that fish viscera are more favorable for the extraction of antioxidant peptides, providing new insights for the practical application of fish by-products. This could increase the utilization of fish viscera and reduce the environmental pollution caused by their waste, offering valuable references for the study and application of antioxidant peptides from fish by-products.

Background: Specialised anti-herbivory metabolites are abundant in the solanaceous genus Nicotiana. These metabolites include the large family of 17-hydroxygeranyllinalool diterpene glycosides (HGL-DTGs). Many HGL-DTGs occur exclusively within the Nicotiana genus, but information from the molecular model species N. tabacum, N. benthamiana, and the tree tobacco N. glauca is limited.

Objectives: We studied HGL-DTG occurrence and complexity in these species with the aim of providing in-depth reference annotations and comprehensive HGL-DTG inventories.

Methods: We analysed polar metabolite extracts in comparison to the previously investigated wild reference species N. attenuata using positive ESI(+) and negative ESI(-) mode electrospray ionisation LC-MS and MS/MS.

Results: We provide annotations of 66 HGL-DTGs with in-source and MS/MS fragmentation spectra for selected HGL-DTGs with exemplary fragment interpretations of ESI(+) as well as less studied ESI(-) spectra. We assemble a potential biosynthesis pathway comparing the presence of HGL-DTGs in N. tabacum, N. glauca, and N. benthamiana to N. attenuata. Approximately one-third of HGL-DTGs are chromatographically resolved isomers of hexose, deoxyhexose, or malonate conjugates. The number of isomers is especially high for conjugates with low numbers of deoxyhexose moieties.

Conclusions: We extend the number of known HGL-DTGs with a focus on Nicotiana model species and demonstrate that the HGL-DTG family of N. tabacum plants can be surprisingly complex. Our study provides an improved basis with detailed references to previous studies of wild Nicotiana species and enables inference of HGL-DTG pathways with required enzymes for the biosynthesis of this important family of specialised defence metabolites.

Background/Objectives: Degenerative musculoskeletal diseases represent a global health problem due to the progressive deterioration of affected individuals. As a bioactive compound, catechins have shown osteoprotective properties by stimulating osteoblastic cells and inhibiting bone resorption. Thus, this review aimed to address the mechanism of action of catechins on bone tissue. Methods: The search was applied to PubMed without limitations in date, language, or article type. Fifteen articles matched the topic and objective of this review. Results: EGCG (epigallocatechin gallate) and epicatechin demonstrated action on the osteogenic markers RANKL, TRAP, and NF-κβ and expression of BMPs and ALP, thus improving the bone microarchitecture. Studies on animals showed the action of EGCG in increasing calcium and osteoprotegerin levels, in addition to regulating the transcription factor NF-ATc1 associated with osteoclastogenesis. However, it did not show any effect on osteocalcin and RANK. Regarding human studies, EGCG reduced the risk of fracture in a dose-dependent manner. In periodontal tissue, EGCG reduced IL-6, TNF, and RANKL in vitro and in vivo. Human studies showed a reduction in periodontal pockets, gingival index, and clinical attachment level. The action of EGCG on membranes and hydrogels showed biocompatible and osteoinductive properties on the microenvironment of bone tissue by stimulating the expression of osteogenic growth factors and increasing osteocalcin and alkaline phosphate levels, thus promoting new bone formation. Conclusions: EGCG stimulates cytokines related to osteogenes, increasing bone mineral density, reducing osteoclastogenesis factors, and showing great potential as a therapeutic strategy for reducing the risk of bone fractures.

Background: The increasing prevalence of autism spectrum disorder (ASD) highlights the need for objective diagnostic markers and a better understanding of its pathogenesis. Metabolic differences have been observed between individuals with and without ASD, but their causal relevance remains unclear.

Methods: Bidirectional two-sample Mendelian randomization (MR) was used to assess causal associations between circulating plasma metabolites and ASD using large-scale genome-wide association study (GWAS) datasets-comprising 1091 metabolites, 309 ratios, and 179 lipids-and three European autism datasets (PGC 2015: n = 10,610 and 10,263; 2017: n = 46,351). Inverse-variance weighted (IVW) and weighted median methods were employed, along with robust sensitivity and power analyses followed by independent cohort validation.

Results: Higher genetically predicted levels of sphingomyelin (SM) (d17:1/16:0) (OR, 1.129; 95% CI, 1.024-1.245; p = 0.015) were causally linked to increased ASD risk. Additionally, ASD children had higher plasma creatine/carnitine ratios. These MR findings were validated in an independent US autism cohort using machine learning analysis.

Conclusion: Utilizing large datasets, two MR approaches, robust sensitivity analyses, and independent validation, our novel findings provide evidence for the potential roles of metabolomics and circulating metabolites in ASD diagnosis and etiology.

Background/Objectives: Over time, the scientific community has developed a growing interest in the effects of mixtures of different compounds, for which there is currently no established evidence or knowledge, in relation to certain categories of xenobiotics. It is well known that exposure to pollutants causes oxidative stress, resulting in the overproduction of reactive oxygen species (ROS), which can affect signaling pathways that regulate the cell cycle, apoptosis, energy balance, and cellular metabolism. The aim of this study was to investigate the effects of sub-lethal concentrations of mixtures of emerging pollutants and pharmaceuticals on the modulation of biomarkers related to toxicity, oxidative stress, and cancer. Methods: In this study, the hepatoma cell line HepG2 was exposed to increasing concentrations of polybrominated diphenyl ether 47 (BDE-47), cadmium chloride (CdCl₂), and carbamazepine (CBZ), both individually and in mixtures, for 72 h to assess cytotoxicity using the MTT assay. The subsequent step, following the identification of the sub-lethal concentration, was to investigate the effects of exposure at the gene expression level, through the evaluation of molecular markers related to cell cycle and apoptosis (p53), oxidative stress (NRF2), conjugation and detoxification of xenobiotics (CYP2C9 and GST), DNA damage (RAD51 and γH2AFX), and SUMOylation processes (SUMO1 and UBC9) in order to identify any potential alterations in pathways that are normally activated at the cellular level. Results: The results showed that contaminants tend to affect the enzymatic detoxification and antioxidant system, influencing DNA repair defense mechanisms involved in resistance to oxidative stress. The combined effect of the compounds at sub-lethal doses results in a greater activation of these pathways compared to exposure to each compound alone, thereby exacerbating their cytotoxicity. Conclusions: The biomarkers analyzed could contribute to the definition of early warning markers useful for environmental monitoring, while simultaneously providing insight into the toxicity and hazard levels of these substances in the environment and associated health risks.

Porcine models are increasingly recognized for their similarities to humans and have been utilized in disease modeling and organ grafting research. While extensive metabolomics studies have been conducted in swine, primarily focusing on conventional cohorts or specific animal models, the composition and functions of fecal metabolites in pigs across different age groups-particularly in the elderly-remain inadequately understood. In this study, an untargeted metabolomics approach was employed to analyze the fecal metabolomes of pigs at three distinct age stages: young (one year), middle-aged (four years), and elderly (eight years). The objective was to elucidate age-associated changes in metabolite composition and functionality under standardized rearing conditions. The untargeted metabolomic analysis revealed a diverse array of age-related metabolites. Notably, L-methionine sulfoxide levels were found to increase with age, whereas cytidine-5-monophosphate levels exhibited a gradual decline throughout the aging process. These metabolites demonstrated alterations across various biological pathways, including energy metabolism, pyrimidine metabolism, lipid metabolism, and amino acid metabolism. Collectively, the identified key metabolites, such as L-methionine sulfoxide and Cholecalciferol, may serve as potential biomarkers of senescence, providing valuable insights into the mechanistic understanding of aging in pigs.

Background: Neonatal rats that receive sucrose during a critical postnatal period (CP, days 12 to 28) develop hypertension by the time they reach adulthood. Inflammation might contribute to changes during this period and could be associated with variations in the vascular smooth muscle (VSMC) phenotype.

Objective: We studied changes in inflammatory pathways that could underlie the expression of the secretory phenotype in the VSMC in the thoracic aorta of rats that received sucrose during CP.

Methods: We analyzed histological changes in the aorta and the expression of the COX-2, TLR4, iNOS, eNOS, MMP-2 and -9, and β- and α-actin, the quantities of TNF-α, IL-6, and IL-1β using ELISA, and the levels of fatty acids using gas chromatography.

Results: The aortic wall presented disorganization, decellularization, and wavy elastic fibers and an increase in the lumen area. The α- and β-actin expressions were decreased, while COX-2, TLR4, TNF-α, and the activity of IL-6 were increased. Oleic acid was increased in CP in comparison to the control group.

Conclusions: There is transient hypertension at the end of the CP that is accompanied by inflammation and a change in the phenotype of VSMC to the secretory phenotype. The inflammatory changes could act as epigenetic signals to determine the development of hypertension when animals reach adulthood.