Metabolites最新文献

Background: Acetyl phosphate (AcP) is a microbial intermediate involved in the central bacterial metabolism. In bacteria, it also functions as a donor of acetyl and phosphoryl groups in the nonenzymatic protein acetylation and signal transduction. In host, AcP was detected as an intermediate of the pyruvate dehydrogenase complex, and its appearance in the blood was considered as an indication of mitochondrial breakdown. In vitro experiments showed that AcP is a powerful agent of nonenzymatic acetylation of proteins. The influence of AcP on isolated mitochondria has not been previously studied.

Methods: In this work, we tested the influence of AcP on the opening of the mitochondrial permeability transition pore (mPTP), respiration, and succinate dehydrogenase (SDH) activity under neutral and alkaline conditions stimulating the nonenzymatic acetylation using polarographic, cation-selective, and spectrophotometric methods.

Results: It was found that AcP slowed down the opening of the mPTP by calcium ions and decreased the efficiency of oxidative phosphorylation and the activity of SDH. These effects were observed only at neutral pH, whereas alkaline pH by itself caused a decrease in these functions to a much greater extent than AcP. AcP at a concentration of 0.5-1 mM decreased the respiratory control and the swelling rate by 20-30%, while alkalization decreased them twofold, thereby masking the effect of AcP. Presumably, the acetylation of adenine nucleotide translocase involved in both the opening of mPTP and oxidative phosphorylation underlies these changes. The intermediate electron carrier phenazine methosulfate (PMS), removing SDH inhibition at the ubiquinone-binding site, strongly activated SDH under alkaline conditions and, partially, in the presence of AcP. It can be assumed that AcP weakly inhibits the oxidation of succinate, while alkalization slows down the electron transfer from the substrate to the acceptor.

Conclusions: The results show that both AcP and alkalization, by promoting nonmetabolic and nonenzymatic acetylation from the outside, retard mitochondrial functions.

Background/Objectives: Dietary patterns, including high-fat and high-carbohydrate diets (HFDs and HCDs), as well as non-dietary factors such as food additives and antibiotics, are strongly linked to metabolic endotoxemia, a critical driver of low-grade chronic inflammation. This review explores the mechanisms through which these factors impair intestinal permeability, disrupt gut microbial balance, and facilitate lipopolysaccharide (LPS) translocation into the bloodstream, contributing to metabolic disorders such as obesity, type 2 diabetes mellitus, and inflammatory bowel disease. Methods: The analysis integrates findings from recent studies on the effects of dietary components and gut microbiota interactions on intestinal barrier function and systemic inflammation. Focus is given to experimental designs assessing gut permeability using biochemical and histological methods, alongside microbiota profiling in both human and animal models. Results: HFDs and HCDs were shown to increase intestinal permeability and systemic LPS levels, inducing gut dysbiosis and compromising barrier integrity. The resulting endotoxemia promoted a state of chronic inflammation, disrupting metabolic regulation and contributing to the pathogenesis of various metabolic diseases. Food additives and antibiotics further exacerbated these effects by altering microbial composition and increasing gut permeability. Conclusions: Diet-induced alterations in gut microbiota and barrier dysfunction emerge as key mediators of metabolic endotoxemia and related disorders. Addressing dietary patterns and their impact on gut health is crucial for developing targeted interventions. Further research is warranted to standardize methodologies and elucidate mechanisms for translating these findings into clinical applications.

Background: Cardiac diseases remain one of the leading causes of death globally, often linked to ischemic conditions that can affect cellular homeostasis and metabolism, which can lead to the development of cardiovascular dysfunction. Considering the effect of ischemic cardiomyopathy on the global population, it is vital to understand the impact of ischemia on cardiac cells and how ischemic conditions change different cellular functions through post-translational modification of cellular proteins. Methods: To understand the cellular function and fine-tuning during stress, we established an ischemia model using neonatal rat ventricular cardiomyocytes. Further, the level of cellular acetylation was determined by Western blotting and affinity chromatography coupled with liquid chromatography-mass spectroscopy. Results: Our study found that the level of cellular acetylation significantly reduced during ischemic conditions compared to normoxic conditions. Further, in mass spectroscopy data, 179 acetylation sites were identified in the proteins in ischemic cardiomyocytes. Among them, acetylation at 121 proteins was downregulated, and 26 proteins were upregulated compared to the control groups. Differentially, acetylated proteins are mainly involved in cellular metabolism, sarcomere structure, and motor activity. Additionally, a protein enrichment study identified that the ischemic condition impacted two major biological pathways: the acetyl-CoA biosynthesis process from pyruvate and the tricarboxylic acid cycle by deacetylation of the associated proteins. Moreover, most differential acetylation was found in the protein pyruvate dehydrogenase complex. Conclusions: Understanding the differential acetylation of cellular protein during ischemia may help to protect against the harmful effect of ischemia on cellular metabolism and cytoskeleton organization. Additionally, our study can help to understand the fine-tuning of proteins at different sites during ischemia.

During the COVID-19 pandemic, omics-based methodologies were extensively used to study the pathological mechanisms of SARS-CoV-2 infection and replication in human cells at a large scale [...].

Background: Volatile compounds have a deep influence on the quality and application of the medicinal herb Artemisia argyi; however, little is known about the effect of UV-B radiation on volatile metabolites. Methods: We herein investigated the effects of UV-B exposure on the volatile compounds and transcriptome of A. argyi to assess the potential for improving its quality and medicinal characteristics. Results: Out of 733 volatiles obtained, a total of 133 differentially expressed metabolites (DEMs) were identified by metabolome analysis. These were classified into 16 categories, primarily consisting of terpenoids, esters, heterocyclic compounds, alcohols, and ketones. Sensory odor analysis indicated that green was the odor with the highest number of annotations. Among the 544 differentially expressed genes (DEGs) identified by transcriptome analysis, most DEGs were linked to "metabolic pathways" and "biosynthesis of secondary metabolites". Integrated analysis revealed that volatiles were mainly synthesized through the shikimate pathway and the MEP pathway. RNA-seq and qPCR results indicated that transcription factors HY5, bHLH25, bHLH18, bHLH148, MYB114, MYB12, and MYB111 were upregulated significantly after UV-B radiation, and were therefore considered key regulatory factors for volatiles synthesis under UV-B radiation. Conclusions: These findings not only provide new insights into UV-induced changes in volatile compounds, but also provide an exciting opportunity to enhance medicinal herbs' value, facilitating the development of products with higher levels of essential oils, flavor, and bioactivity.

Background/objectives: The acute stress response affects brain metabolites closely linked to the tricarboxylic acid (TCA) cycle. This response involves time-dependent changes in hormones and neurotransmitters, which contribute to resilience and the ability to adapt to acute stress while maintaining homeostasis. This physiological mechanism of metabolic dynamics, combined with time-series analysis, has prompted the development of new methods to observe the relationship between TCA cycle-related brain metabolites. This study aimed to observe the acute stress response through metabolic interactions using time-series proton magnetic resonance spectroscopy (1H-MRS) in the left hippocampus of mice.

Methods: In this study, 4-week-old male C57BL/6N mice (n = 24) were divided into control (n = 12) and acute stress groups (n = 12). Acute stress was induced through a 2 h restraint protocol. Time-series 1H-MRS data were obtained on the left hippocampus of both groups using a 9.4 T 1H-MRS scanner. Time-series MRS data were quantified using LCModel, and significant metabolic interactions were identified through Spearman correlation analysis, a one-tailed sign test, and false discovery rate correction.

Results: No significant metabolic correlation coefficient was observed in the control group. However, in the acute stress group, glutathione (GSH) and N-acetyl aspartate (NAA) showed a significant positive correlation over time, with a high correlation coefficient exceeding 0.5.

Conclusions: Temporal measurement of GSH and NAA, combined with correlation analysis, offers a comprehensive understanding for the metabolic dynamics during acute stress. This approach emphasizes their distinct roles and interdependence in the progression of oxidative stress, mitochondrial function, and the maintenance of physiological homeostasis.

Background: ALDH1L1 plays a crucial role in folate metabolism, regulating the flow of one-carbon groups through the conversion of 10-formyltetrahydrofolate to tetrahydrofolate and CO₂ in a NADP⁺-dependent reaction. The downregulation of ALDH1L1 promotes malignant tumor growth, and silencing of ALDH1L1 is commonly observed in many cancers. In a previous study, Aldh1l1 knockout (KO) mice were found to have an altered liver metabotype, including significant alterations in glycine and serine. Serine and glycine play crucial roles in pathways linked to cancer initiation and progression, including one-carbon metabolism. Objective/Methods: To further investigate the metabolic role of ALDH1L1, an untargeted metabolomic analysis was conducted on the liver and plasma of both KO and wild-type (WT) male and female mice. Since ALDH1L1 affects glycine- and serine-coupled metabolites and metabolic pathways, correlation analyses between liver glycine and serine with other liver or plasma metabolites were performed for both WT and KO mice. Significantly correlated metabolites were input into MetaboAnalyst 5.0 for pathway analysis to uncover metabolic pathways coupled with serine and glycine in the presence or absence of ALDH1L1 expression. Results: This analysis showed substantial alterations in pathways associated with glycine and serine following ALDH1L1 loss, including the amino acid metabolism, antioxidant pathways, fatty acid oxidation, and vitamin B5 metabolism. These results indicate the glycine- and serine-linked metabolic reprogramming following ALDH1L1 loss to support macromolecule biosynthesis and antioxidant defense. Additional research is required to further explore the correlation between specific alterations in these pathways and tumor growth, as well as to identify potential dietary interventions to mitigate the detrimental effects of ALDH1L1 loss.

Background/objectives: Acupuncture is an efficacious integrative therapy for treating pain, fatigue, and sleep disturbance (the psychoneurological symptom cluster) in breast cancer survivors. However, the mechanisms underlying its effects remain unclear, and related metabolomics studies are limited. This study aimed to examine serum metabolite changes after acupuncture and their relationships to symptom improvement.

Methods: Forty-two breast cancer survivors experiencing pain, fatigue, and sleep disturbance participated in a single-arm acupuncture trial. They received a 10-session acupuncture intervention over 5 weeks. Fasting blood samples and symptom surveys were collected before and after the acupuncture intervention, and untargeted metabolomics profiling was conducted on serum samples. Mixed-effects models adjusting for covariates (age, race, body mass index, and antidepressant use) were applied for analysis.

Results: After acupuncture, there was a significant reduction in the psychoneurological symptom cluster (mean reduction = -6.2, p < 0.001).Bonferroni correction was applied to 40 independent metabolite clusters (α = 0.00125); cysteine-glutathione disulfide (p = 0.0006) significantly increased, and retinal (p = 0.0002) and cis-urocanate (p = 0.0005) were significantly decreased. Dimethyl sulfone (p = 0.00139) showed a trend towards reduction after acupuncture and its change (p = 0.04, β =1.97) was positively associated with reduction in the psychoneurological symptom cluster. Also, increased lauroylcarnitine (p = 0.0009) and decreased cytosine (p = 0.0008) can modulate the therapeutic effects of acupuncture.

Conclusions: Acupuncture demonstrates beneficial effects on the psychoneurological symptom cluster in breast cancer survivors. Dimethyl sulfone may be a promising mediator in the relationship between acupuncture and psychoneurological symptoms, while acylcarnitine metabolism may modulate the therapeutic effect of acupuncture.

TCIPP (tris(1,3-dichloro-2-propyl) phosphate) and TCEP (tris(2-chloroethyl) phosphate) are organophosphate ester flame retardants found in various consumer products, posing significant health and environmental risks through inhalation, ingestion, and dermal exposure. Research reveals these compounds cause oxidative stress, inflammation, endocrine disruption, genotoxicity, neurotoxicity, and potentially hepatotoxicity, nephrotoxicity, cardiotoxicity, developmental, reproductive, and immunotoxicity. This review summarizes the current knowledge on the toxicological mechanisms of TCIPP and TCEP and presents the latest data on their toxicological effects obtained in vitro and in vivo, using omic systems, and on the basis of computational modelling. It also elaborates on the scope of further toxicities and highlights the necessity of ongoing mechanistic research, integration of new technologies, and successful transfer of the acquired knowledge into risk evaluation, policies and regulations, and the creation of safer products. Since flame retardants are already present in homes, schools, offices, and daycare centres, efforts to scale back the exposure to these chemicals, most especially the hazardous ones, must be made to protect human health and the environment. Therefore, effective and timely prevention, based upon a deep knowledge of the entire toxicological profile of these substances, is the only way to face this difficult toxicological issue and provide for a healthy and safe future.

Background: Weissella confusa is a member of the lactic acid bacterium group commonly found in many salt-fermented foods. Strains of W. confusa isolated from high-salinity environments have been shown to tolerate salt stress to some extent. However, the specific responses and mechanisms of W. confusa under salt stress are not fully understood.

Methods: To study the effect of NaCl stress on W. confusa, growth performance and metabolite profiles of the strains were compared between a NaCl-free group and a 35% NaCl-treated group. Growth performance was assessed by measuring viable cell counts and examining the cells using scanning electron microscopy (SEM). Intracellular and extracellular metabolites were analyzed by non-targeted metabolomics based on liquid chromatography-mass spectrometry (LC-MS).

Results: It was found that the viable cell count of W. confusa decreased with increasing salinity, and cells could survive even in saturated saline (35%) medium for 24 h. When exposed to 35% NaCl, W. confusa cells exhibited surface pores and protein leakage. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, 42 different metabolites were identified in the cells and 18 different metabolites in the culture medium. These different metabolites were mainly involved in amino acid metabolism, carbohydrate metabolism, and nucleotide metabolism. In addition, salt-exposed cells exhibited higher levels of intracellular ectoine and lactose, whose precursors, such as aspartate, L-2,4-diaminobutanoate, and galactinol, were reduced in the culture medium.

Conclusions: This study provides insight into the metabolic responses of W. confusa under salt stress, revealing its ability to maintain viability and alter metabolism in response to high NaCl concentrations. Key metabolites such as ectoine and lactose, as well as changes in amino acid and nucleotide metabolism, may contribute to its tolerance to salt. These findings may improve our understanding of the bacterium's survival mechanisms and have potential applications in food fermentation and biotechnology.