PubMed

ACS Chem Neurosci. 2024 Aug 23. doi: 10.1021/acschemneuro.4c00355. Online ahead of print.ABSTRACTParkinson's disease (PD) is a neurodegenerative disorder characterized by diverse symptoms, where accurate diagnosis remains challenging. Traditional clinical observation methods often result in misdiagnosis, highlighting the need for biomarker-based diagnostic approaches. This study utilizes ultraperformance liquid chromatography coupled to an electrospray ionization source and quadrupole time-of-flight untargeted metabolomics combined with biochemometrics to identify novel serum biomarkers for PD. Analyzing a Brazilian cohort of serum samples from 39 PD patients and 15 healthy controls, we identified 15 metabolites significantly associated with PD, with 11 reported as potential biomarkers for the first time. Key disrupted metabolic pathways include caffeine metabolism, arachidonic acid metabolism, and primary bile acid biosynthesis. Our machine learning model demonstrated high accuracy, with the Rotation Forest boosting model achieving 94.1% accuracy in distinguishing PD patients from controls. It is based on three new PD biomarkers (downregulated: 1-lyso-2-arachidonoyl-phosphatidate and hypoxanthine and upregulated: ferulic acid) and surpasses the general 80% diagnostic accuracy obtained from initial clinical evaluations conducted by specialists. Besides, this machine learning model based on a decision tree allowed for visual and easy interpretability of affected metabolites in PD patients. These findings could improve the detection and monitoring of PD, paving the way for more precise diagnostics and therapeutic interventions. Our research emphasizes the critical role of metabolomics and machine learning in advancing our understanding of the chemical profile of neurodegenerative diseases.PMID:39177430 | DOI:10.1021/acschemneuro.4c00355

J Sci Food Agric. 2024 Aug 23. doi: 10.1002/jsfa.13807. Online ahead of print.ABSTRACTBACKGROUND: The present study evaluated the effects of temperature, pH, light and chemical oxidation on fucoxanthin changes in terms of colour, antioxidant activity and metabolomic profile. Additionally, the correlation between antioxidant activity and identified metabolites was analysed.RESULTS: It was found that colour change was significantly reduced at elevated heat (100 °C, *∆E = 0.81 ± 0.05), reduced pH (pH 3, *∆E = 0.59 ± 0.04) and length of light exposure (*∆E = 3.16 ± 0.04). Antioxidant activity decreased under all treatments. Among the temperatures tested, fucoxanthin exhibited the highest activity at 60 °C, ranging from 0.92 to 3.04 mg Trolox equivalents (TE) g-1. Significant activity reductions (P < 0.05) were observed as a result of pH changes in the 2,2-diphenyl-1-picrylhydrazyl and β-carotene bleaching assays. Exposure to light 2: warm white lamp for 120 h significantly reduced antioxidant activity (0.01 to 1.70 mg TE g-1). Chemical oxidation also led to reduced activity, ranging from 0.18 to 0.29 mg TE g-1. Multivariate data analysis revealed distinct profiles for temperature, pH, light and chemical oxidation treatments. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomics analysis identified 10 metabolites, and significant correlations (P < 0.05) indicate that these metabolites contributed to the samples' antioxidant activities.CONCLUSION: In conclusion, fucoxanthin tolerates well at 60 °C, within pH range 3-9, and within 8 h of light exposure, as indicated by its consistent antioxidant activity and minimal colour change. Each treatment resulted in distinct metabolite concentrations, as shown by LC-MS/MS-based metabolomics analysis. Further research into these metabolites could advance the understanding of their roles and aid in optimising processing conditions to favour beneficial metabolites. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.PMID:39177277 | DOI:10.1002/jsfa.13807

Virulence. 2024 Aug 23:2395833. doi: 10.1080/21505594.2024.2395833. Online ahead of print.ABSTRACTBACKGROUND: Fatty acid metabolism constitutes a significant and intricate biochemical process within microorganisms. Cytochrome P450 (CYP450) enzymes are found in most organisms and occupy a pivotal position in the metabolism of fatty acids. However, the role of CYP450 enzyme mediated fatty acid metabolism in the pathogenicity of pathogenic fungi remains unclear.METHODS: In this study, a CYP450 enzyme-encoding gene, SsCYP86, was identified in the sugarcane smut fungus Sporisorium scitamineum and its functions was characterized using a target gene homologous recombination strategy and metabonomics.RESULTS: We found that the expression of SsCYP86 was induced by or sugarcane wax or under the condition of mating/filamentation. Sexual reproduction assay demonstrated that the SsCYP86 deletion mutant was defective in mating/filamentation and significantly reduced its pathogenicity. Further fatty acid metabolomic analysis unravelled the levels of fatty acid metabolites were reduced in the SsCYP86 deletion mutant. Exogenous addition of fatty acid metabolites cis-11-eicosenoic acid (C20:1N9), pentadecanoic acid (C15:0), and linolenic acid (C18:3N3) partially restored the mating/filamentation ability of the SsCYP86 deletion mutant and restored the transcriptional level of the SsPRF1, a pheromone response transcription factor that is typically down-regulated in the absence of SsCYP86. Moreover, the constitutive expression of SsPRF1 in the SsCYP86 deletion mutant restored its mating/filamentation.CONCLUSION: Our results indicated that SsCyp86 modulates the SsPRF1 transcription by fatty acid metabolism, and thereby regulate the sexual reproduction of S. scitamineum. These findings provide insights into how CYPs regulate sexual reproduction in S. scitamineum.PMID:39177034 | DOI:10.1080/21505594.2024.2395833

Food Chem X. 2024 Jul 22;23:101688. doi: 10.1016/j.fochx.2024.101688. eCollection 2024 Oct 30.ABSTRACTMulti-omics techniques were combined with microstructure, molecular sensory science and non-volatile matrices for the first time to investigate variations in organic macromolecules and flavor in caviar during preservation. After 4-6 weeks of storage, the peroxide value was 35.38 mg/g and the accumulation of thiobarbiturates was significant with caviar membranes exhibiting a decrease in elasticity and an increase in viscosity. Sixteen key volatile compounds were detected by GC-MS, while the volatile compounds that contributed to the differences in caviar flavor at different storage times were mainly tetradecane, (E)-2-hexenal, and heptanal. The pathways associated with flavor release during storage were mainly abundant in the linolenic acid metabolism, alanine metabolism, and glycerophospholipid metabolism pathways. The correlation of 11 differential proteins and 24 differential lipids with odorants was further explored, such as arginine, proline, alanine, PE (20:4/22:6), PE (16:1/18:2), and PE (20:5/18:2). Overall, Aspartate, glutamate, oleic acid, linoleic acid, and phospholipids enriched in C22:6 and C18:2 chains are potential metabolic markers. This study provides a basis from a multi-omics perspective for the investigation of the relationship between quality deterioration and precursor metabolism in caviar storage process.PMID:39176039 | PMC:PMC11339060 | DOI:10.1016/j.fochx.2024.101688

J Inflamm Res. 2024 Aug 17;17:5521-5531. doi: 10.2147/JIR.S461621. eCollection 2024.ABSTRACTPURPOSE: The aim of this study was to investigate the changes of different metabolites in the body fluids of non-dialysis patients with chronic kidney disease (CKD) using a metabolomics approach. The goal was to identify early biomarkers of CKD progression through metabolic pathway analysis.PATIENTS AND METHODS: Plasma samples from 47 patients with stages 1-4 CKD not requiring dialysis and 30 healthy controls were analyzed by liquid chromatography-mass spectrometry (LC-MS). Using multivariate data analysis, specifically a partially orthogonal least squares discriminant analysis model (OPLS-DA), we investigated metabolic differences between different stages of CKD. The sensitivity and specificity of the analysis were evaluated using the Area Under Curve (AUC) method. Furthermore, the metabolic pathways were analyzed using the Met PA database.RESULTS: Plasma samples from CKD patients and controls were successfully differentiated using an OPLS-DA model. Initially, twenty-five compounds were identified as potential plasma metabolic markers for distinguishing CKD patients from healthy controls. Among these, six compounds (ADMA, D-Ornithine, Kynurenine, Kynurenic acid, 5-Hydroxyindoleacetic acid, and Gluconic acid) were found to be associated with CKD progression It has been found to be associated with the progression of CKD. Changes in metabolic pathways associated with CKD progression include arginine and ornithine metabolism, tryptophan metabolism, and the pentose phosphate pathway.CONCLUSION: By analyzing the metabolic pathways of different metabolites, we have identified the significant impact of CKD progression. The main metabolic pathways involved are Arginine and Ornithine metabolism, Tryptophan metabolism, and Pentose phosphate pathway. ADMA, D-Ornithine, L-Kynurenine, Kynurenic acid, 5-Hydroxyindoleacetic acid, and Gluconic acid could serve as potential early biomarkers for CKD progression. These findings have important implications for the early intervention and treatment of CKD, as well as for further research into the underlying mechanisms of its pathogenesis.PMID:39176038 | PMC:PMC11339343 | DOI:10.2147/JIR.S461621

Front Nutr. 2024 Aug 8;11:1442535. doi: 10.3389/fnut.2024.1442535. eCollection 2024.ABSTRACTBACKGROUND: Radish seed is a functional food with many beneficial health effects. Glucosinolates are characteristic components in radish seed that can be transformed into bioactive isothiocyanates by gut microbiota.OBJECTIVE: The present study aims to assess anti-obesity efficacy of radish seed glucosinolates (RSGs) and explored the underlying mechanisms with a focus on gut microbiota and fecal metabolome.METHODS: High-fat diet-induced obese mice were supplemented with different doses of RSGs extract for 8 weeks. Changes in body weight, serum lipid, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels; and pathological changes in the liver and adipose tissue were examined. Fecal metabolome and 16S rRNA gene sequencing were used to analyze alterations in fecal metabolite abundance and the gut microbiota, respectively.RESULTS AND CONCLUSION: Results showed that RSG extract prevented weight gain and decreased serum lipid, ALT, AST levels and lipid deposition in liver and epididymal adipocytes in obese mice. Treatment with RSG extract also increased gut microbiota diversity and altered the dominant bacteria genera in the gut microbiota, decreasing the abundance of Faecalibaculum and increasing the abundance of Allobaculum, Romboutsia, Turicibacter, and Akkermansia. Fecal metabolome results identified 570 differentially abundant metabolites, of which glucosinolate degradation products, such as sulforaphene and 7-methylsulfinylheptyl isothiocyanate, were significantly upregulated after RSG extract intervention. Furthermore, enrichment analysis of metabolic pathways showed that the anti-obesity effects of RSG extract may be mediated by alterations in bile secretion, fat digestion and absorption, and biosynthesis of plant secondary metabolites. Overall, RSG extract can inhibit the development of obesity, and the obesity-alleviating effects of RSG are related to alternative regulation of the gut microbiota and glucosinolate metabolites.PMID:39176030 | PMC:PMC11340518 | DOI:10.3389/fnut.2024.1442535

Exploration (Beijing). 2024 Jan 23;4(4):20230064. doi: 10.1002/EXP.20230064. eCollection 2024 Aug.ABSTRACTSelf-assembled peptides have been among the important biomaterials due to its excellent biocompatibility and diverse functions. Over the past decades, substantial progress and breakthroughs have been made in designing self-assembled peptides with multifaceted biomedical applications. The techniques for quantitative analysis, including imaging-based quantitative techniques, chromatographic technique and computational approach (molecular dynamics simulation), are becoming powerful tools for exploring the structure, properties, biomedical applications, and even supramolecular assembly processes of self-assembled peptides. However, a comprehensive review concerning these quantitative techniques remains scarce. In this review, recent progress in techniques for quantitative investigation of biostability, cellular uptake, biodistribution, self-assembly behaviors of self-assembled peptide etc., are summarized. Specific applications and roles of these techniques are highlighted in detail. Finally, challenges and outlook in this field are concluded. It is believed that this review will provide technical guidance for researchers in the field of peptide-based materials and pharmaceuticals, and facilitate related research for newcomers in this field.PMID:39175887 | PMC:PMC11335468 | DOI:10.1002/EXP.20230064

J Pharm Anal. 2024 Jul;14(7):100973. doi: 10.1016/j.jpha.2024.100973. Epub 2024 Mar 28.ABSTRACTPolygala tenuifolia, commonly known as Yuanzhi (YZ) in Chinese, has been shown to possess anti-insomnia properties. However, the material basis and the mechanism underlying its sedative-hypnotic effects remain unclear. Herein, we investigated the active components and neurochemical mechanism of YZ extracts using liquid chromatography tandem mass spectrometry (LC-MS/MS)-based pharmacometabolomics and mass spectrometry imaging (MSI)-based spatial resolved metabolomics. According to the results, 17 prototypes out of 101 ingredients in the YZ extract were detected in both the plasma and brain, which might be the major components contributing to the sedative-hypnotic effects. Network pharmacology analysis revealed that these prototypes may exert their effects through neuroactive ligand-receptor interaction, serotonergic synapse, dopaminergic synapse, and dopaminergic synapse, among other pathways. LC-MS/MS-based targeted metabolomics and Western blot (WB) revealed that tryptophan-serotonin-melatonin (Trp-5-HT-Mel) and tyrosine-norepinephrine-adrenaline (Tyr-Ne-Ad) are the key regulated pathways. Dopa decarboxylase (DDC) upregulation and phenylethanolamine N-methyltransferase (PNMT) downregulation further confirmed these pathways. Furthermore, MSI-based spatially resolved metabolomics revealed notable alterations in 5-HT in the pineal gland (PG), and Ad in the brainstem, including the middle brain (MB), pons (PN), and hypothalamus (HY). In summary, this study illustrates the efficacy of an integrated multidimensional metabolomics approach in unraveling the sedative-hypnotic effects and neurochemical mechanisms of a Chinese herbal medicine, YZ.PMID:39175609 | PMC:PMC11340588 | DOI:10.1016/j.jpha.2024.100973

Front Endocrinol (Lausanne). 2024 Aug 8;15:1375896. doi: 10.3389/fendo.2024.1375896. eCollection 2024.ABSTRACTBACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is a common chronic inflammatory bowel disease characterized by diarrhea and abdominal pain. Recently human metabolites have been found to help explain the underlying biological mechanisms of diseases of the intestinal system, so we aimed to assess the causal relationship between human blood metabolites and susceptibility to IBD subtypes.METHODS: We selected a genome-wide association study (GWAS) of 275 metabolites as the exposure factor, and the GWAS dataset of 10 IBD subtypes as the outcome, followed by univariate and multivariate analyses using a two-sample Mendelian randomization study (MR) to study the causal relationship between exposure and outcome, respectively. A series of sensitivity analyses were also performed to ensure the robustness of the results.RESULTS: A total of 107 metabolites were found to be causally associated on univariate analysis after correcting for false discovery rate (FDR), and a total of 9 metabolites were found to be significantly causally associated on subsequent multivariate and sensitivity analyses. In addition we found causal associations between 7 metabolite pathways and 6 IBD subtypes.CONCLUSION: Our study confirms that blood metabolites and certain metabolic pathways are causally associated with the development of IBD subtypes and their parenteral manifestations. The exploration of the mechanisms of novel blood metabolites on IBD may provide new therapeutic ideas for IBD patients.PMID:39175573 | PMC:PMC11338916 | DOI:10.3389/fendo.2024.1375896

Front Plant Sci. 2024 Aug 8;15:1332426. doi: 10.3389/fpls.2024.1332426. eCollection 2024.ABSTRACTINTRODUCTION: Cadmium (Cd) is a highly toxic trace element that occurs in large quantities in agricultural soils. The cultivation of industrial crops with high phytoremediation potential, such as kenaf, could effectively reduce soil Cd contamination, but the mechanisms of toxicity, tolerance, and detoxification remain unclear.METHODS: In this study, the effects of different Cd concentrations (0, 100, 250, and 400 µM) on growth, biomass, Cd uptake, physiological parameters, metabolites and gene expression response of kenaf were investigated in a hydroponic experiment.RESULTS AND DISCUSSION: The results showed that Cd stress significantly altered the ability of kenaf to accumulate and transport Cd; increased the activity of hydrogen peroxide (H2O2), superoxide anion (O2 -), and malondialdehyde (MDA); reduced the activities of superoxide dismutase (SOD) and catalase (CAT); and decreased the content of photosynthetic pigments, resulting in significant changes in growth and biomass production. Exposure to Cd was found to have a detrimental effect on the ascorbate-glutathione (AsA-GSH) cycle in the roots, whereas it resulted in an elevation in AsA levels and a reduction in GSH levels in the leaves. The increased content of cell wall polysaccharides under Cd stress could contribute to Cd retention in roots and limited Cd transport to above-ground plant tissues. Metabolomic analyses revealed that alanine, aspartate, and glutamate metabolism, oxidative phosphorylation, ABC transporter, and carbon metabolism were the major metabolic pathways associated with Cd stress tolerance. Cd stress increased gene expression of IRT1 and MTP1 in roots, which resulted in kenaf roots accumulating high Cd concentrations. This study extends our knowledge of the factors regulating the response of kenaf to Cd stress. This work provided a physiological and metabolomic perspective on the mechanism controlling the response of kenaf to Cd stress.PMID:39175486 | PMC:PMC11340530 | DOI:10.3389/fpls.2024.1332426

Plant J. 2024 Aug 23. doi: 10.1111/tpj.16992. Online ahead of print.ABSTRACTIn plants, exposure to high light irradiation induces various stress responses, which entail complex metabolic rearrangements. To explore these dynamics, we conducted time‐course experiments spanning 2 min to 72 h with Arabidopsis thaliana under high and control light. Comparative metabolomics, transcriptomics, redox proteomics, and stable isotope labeling on leaf rosettes identified a series of synchronous and successive responses that provide a deeper insight into well‐orchestrated mechanisms contributing to high‐light acclimation. We observed transient transcriptome downregulation related to light harvesting and electron flow before the profound remodeling of the photosynthetic apparatus. Throughout the entire time course, redox homeostasis is tightly balanced between downregulation of production and enhanced transformation of NADPH accompanied by redistribution of reducing equivalents across several subcellular compartments. In both light conditions, C4 acids such as malate and fumarate are produced via anaplerosis. In carbon units, their accumulation in vacuoles surpasses plastidic levels of starch and intensifies notably under high light. In parallel, citrate synthesis from pyruvate is significantly hindered diurnally. Isotopic labeling in 2‐oxoglutarate and glutamate suggests a moderate de novo synthesis of C5 acids from a vacuolar citrate reservoir during the light phase while they are largely renewed during the night. In the absence of a diurnal clockwise flow through the tricarboxylic acid (TCA) cycle, increased oxidation of photorespiratory glycine takes over as a source of reductants to fuel mitochondrial ATP production. These findings, along with previous research, contribute to a model integrating redox balance and linking increased carbon assimilation and nitrogen metabolism, especially in the context of an incomplete TCA cycle.PMID:39175460 | DOI:10.1111/tpj.16992

Biomed Chromatogr. 2024 Aug 23:e5996. doi: 10.1002/bmc.5996. Online ahead of print.ABSTRACTMolnupiravir (MO) is a pyrimidine nucleoside anti-SARS-CoV-2 drug. MO treatment could cause mild liver injury. However, the underlying mechanism of MO-induced liver injury and the metabolic pathway of MO in vivo are unclear. In this study, metabolomics analysis and molecular biology methods were used to explore these issues. Through metabolomics analysis, it was found that the homeostasis of pyrimidine, purine, lysophosphatidylcholine (LPC), and amino acids in mice was destroyed after MO treatment. A total of 80 changed metabolites were detected. Among these changed metabolites, 4-ethylphenyl sulfate, dihydrouracil, and LPC 20:0 was related to the elevation of alkaline phosphatase (ALP), interleukin-6 (IL6), and nuclear factor kappa-B (NF-κB). The levels of 4-ethylphenyl sulfate, dihydrouracil, and LPC 20:0 in plasma were positively correlated with their levels in the liver, suggesting that these metabolites were associated with MO-induced liver injury. MO treatment could increase NHC and cytidine levels, activate cytidine deaminase (CDA), and increase LPC levels. CDA and LPC could increase the mRNA expression level of toll-like receptor (TLR). The current study indicated that the elevation of hepatic TLR may be an important reason for MO leading to the liver injury.PMID:39175367 | DOI:10.1002/bmc.5996

Zh Nevrol Psikhiatr Im S S Korsakova. 2024;124(7. Vyp. 2):7-15. doi: 10.17116/jnevro20241240727.ABSTRACTInvestigation of multiple sclerosis (MS) pathogenesis requires sophisticated analytical tools of precision medicine, such as omics research, which include genomics, microbiomics and metabolomics (proteomics, lipidomics and glycomics). Such sensitive methods are based on careful preanalytical work with biomaterials to maintain quality and obtain objective results. Implementation of biobanking as a universal method for working with biomaterials will help to standardize the stages of research, compare different scientific team's results. Collaboration of MS researchers with large biobanks can also help to conduct multicenter and long-term prospective studies, to include a wide number of patients. In this article, we analyze the experience of biobanking practice technologies in studies of MS patients and share the experience of partnership between the Center for MS of the Tomsk Region and the Bank of Biological Material of the Siberian State Medical University.PMID:39175234 | DOI:10.17116/jnevro20241240727

J Food Sci. 2024 Aug 22. doi: 10.1111/1750-3841.17308. Online ahead of print.ABSTRACTTo understand the effects and related potential mechanism of H2O2 on pigment metabolism in postharvest broccoli, an integrated analysis of transcriptome and metabolome was performed. Results suggested that 65 differentially expressed genes and 26 differentially accumulated metabolites involved in chlorophyll, carotenoid, and flavonoid metabolism were identified. H2O2 treatment delayed the decrease of chlorophyll content by upregulating the expressions of chlorophyll synthetic genes, thylakoid synthetic genes, and 15 light-harvesting complex genes compared with the control and diphenylene iodonium treatments. H2O2 treatment decreased the accumulation of 11 flavonoids and 5 flavonols by downregulating the flavonoid synthetic genes. In addition, H2O2 treatment promoted carotenoid biosynthesis to eliminate reactive oxygen species in thylakoids, thereby protecting chlorophyll molecules from degradation. The inhibition of flavonoids and flavonols accumulation and chlorophyll decrease was the crucial reason for the delayed yellowing in H2O2 treatment. This study provides a new method and theoretical support for delaying the yellowing process in postharvest broccoli.PMID:39175179 | DOI:10.1111/1750-3841.17308

J Adv Res. 2024 Aug 20:S2090-1232(24)00364-3. doi: 10.1016/j.jare.2024.08.020. Online ahead of print.ABSTRACTINTRODUCTION: Bentazon (BNTZ) is a selective contact herbicide widely used to control field weeds for crop production. Excessive use of BNTZ leads to its accumulation in soils and crops, becoming an environmental contaminant. Therefore, investigation of the mechanisms for BNTZ detoxification and degradation in crops is fundamentally important to reduce crop contamination and ensure food safety.OBJECTIVES: This study aims to elucidate the mechanism of detoxification and degradation pathways of the BNTZ complex in rice by creating transgenic lines expressing a rice ATP-binding cassette (OsABC) transporter gene through genetic engineering techniques combined with chemical analytical techniques and metabolomics approaches.METHODS: We established the rice transgenic lines overexpressing (OE) a rice OsABC transporter and its knockout lines by CRISPR-Cas9 to characterize the gene function and measured the accumulation of BNTZ residues in rice. The metabolites of BNTZ were characterized by LC/Q-TOF-HRMS/MS (Liquid chromatography/time of flight-high resolution mass spectrometry).RESULTS: Overexpression of OsABC significantly conferred rice resistance to BNTZ toxicity by increasing plant elongation, dry weight, and chlorophyll content, and significantly reducing cell membrane damage and BNTZ accumulation in rice tissues. Six different metabolites and ten conjugates were well defined in chemical structures. The reduced BNTZ levels and degradation products in the grains of the OE lines supported the robust activity of the OsABC gene function. Using UPLC-Q-TOF/MS, we further identified accumulated basic metabolites of various carbohydrates, amino acids, hormones, and flavonoids, and found that these metabolites involved in BNTZ degradation were increased more in OE lines than in wild-type (WT) rice.CONCLUSIONS: Our work demonstrates that the OsABC transporter plays a critical role in regulating the mobility and degradative metabolism of BNTZ in rice, thus revealing a regulatory mechanism underlying rice resistance to BNTZ toxicity and adaptation to the environmental stress.PMID:39173875 | DOI:10.1016/j.jare.2024.08.020

Environ Pollut. 2024 Aug 20:124776. doi: 10.1016/j.envpol.2024.124776. Online ahead of print.ABSTRACTAcrolein is a widespread contaminant found in both diet and environment, entering the human body through food, alcohol, smoking, and exposure to fuel combustion fumes. While prior studies have highlighted acrolein's harmful impact on oocyte quality and early embryonic development in vitro, the specific mechanisms by which acrolein affects the female reproductive system in vivo remain poorly understood. This study first confirmed that in vitro acrolein exposure disrupts spindle morphology and chromosome alignment during the mid-MI stage of oocyte development, thus hindering oocyte maturation. Besides, exposure to acrolein not only stunts growth in mice but also impairs ovarian development, decreases the ovarian coefficient, disrupts follicular development, and increases the count of atretic follicles in vivo. Additional research has shown that acrolein exposure reduces the activity of key enzymes in glycolysis, pyruvate metabolism, and the tricarboxylic acid cycle within the ovaries. It also suppresses mitochondrial complex expression and disturbs the balance between mitochondrial fission and fusion, as confirmed by metabolomic analyses. Moreover, acrolein exposure in vivo induced granulosa cell apoptosis and reduced oocyte number. In summary, acrolein exposure impairs glucose metabolism and induces mitochondrial dysfunction in the ovaries.PMID:39173867 | DOI:10.1016/j.envpol.2024.124776

Sci Total Environ. 2024 Aug 20:175680. doi: 10.1016/j.scitotenv.2024.175680. Online ahead of print.ABSTRACTWe investigated the effects of different nanoplastic (NP, size = 100 nm) concentrations on red crayfish (Cherax quadricarinatus) and examined toxicity mechanisms. We established four concentration groups (control (CK): 0 μg/L; Low: 100 μg/L; Medium: 500 μg/L; and High: 1000 μg/L) and analyzed toxicity effects in C. quadricarinatus hepatopancreas using histopathological, transcriptomic, metabolomic, and fluorescence methods. NP exposure caused histological lesions and oxidative stress in hepatopancreas, and also significantly decreased glutathione (GSH) (P < 0.05) but significantly increased malondialdehyde content (MDA) (P < 0.05) in NP-treated groups. By analyzing different metabolic indicators, total cholesterol (T-CHO) content significantly increased (P < 0.05) and triglyceride (TG) content significantly decreased in Medium and High (P < 0.05). Transcriptomic analyses revealed that NPs influenced apoptosis, drug metabolism-cytochrome P450, and P53 signaling pathways. Metabolomic analyses indicated some metabolic processes were affected by NPs, including bile secretion, primary bile acid biosynthesis, and cholesterol metabolism. Caspase 3, 8, and 9 distribution levels in hepatopancreatic tissues were also determined by immunofluorescence; positive caspase staining increased with increased NP concentrations. Additionally, by examining relative Bcl-2, Bax, Apaf-1, and p53 mRNA expression levels, Bcl-2 expression was significantly decreased with increasing NP concentrations; and the expression of Bcl-2 was increasing significantly with the NPs concentration increasing. Bax expression in Low, Medium, and High groups was also significantly higher when compared with the CK group (P < 0.05); with High group levels significantly higher than in Low and Medium groups (P < 0.05). P53 expression was significantly increased in Low, Medium, and High groups (P < 0.05). Thus, NPs induced apoptosis in C. quadricarinatus hepatopancreatic cells, concomitant with increasing NP concentrations. Therefore, we identified mechanisms underpinning NP toxicity in C. quadricarinatus and provide a theoretical basis for exploring NP toxicity in aquatic organisms.PMID:39173758 | DOI:10.1016/j.scitotenv.2024.175680

J Thorac Cardiovasc Surg. 2024 Aug 20:S0022-5223(24)00699-8. doi: 10.1016/j.jtcvs.2024.08.015. Online ahead of print.ABSTRACTOBJECTIVE: Previous reports showed enhanced graft function in both healthy and injured porcine lungs after preservation at 10°C. The objective of the study is to elucidate the mechanism of lung protection by 10°C and identify potential therapeutic targets to improve organ preservation.METHODS: Metabolomics data was analyzed from healthy and injured porcine lungs that underwent extended hypothermic preservation on ice and at 10°C. Tissue sampled before and after preservation were subjected to untargeted metabolic profiling. Principal component analysis (PCA) was performed to test for the separability of the paired samples. Significantly changed metabolites between the two timepoints were identified and analyzed to determine the underlying metabolic pathways. The levels of respiratory activity of lung tissue at hypothermic temperatures were confirmed using high resolution respirometry.RESULTS: In both healthy and injured lungs (n=5 per intervention), PCA suggested minimal change in metabolites after ice preservation, but significant change of metabolites after 10°C preservation, which was associated with significantly improved lung function as assessed by ex vivo lung perfusion (EVLP) and lung transplantation. For healthy lungs, lipid energy pathway was found primarily active at 10°C. For injured lungs, additional carbohydrate energy pathway and anti-ferroptosis pathways aiding organ repair were identified. These metabolic features are also key features involved in mammal hibernation.CONCLUSION: Untargeted metabolomics revealed a dynamic metabolic gradient for lungs stored at 10°C. Elucidating the underlying mechanisms behind this pathway regulation may lead to strategies that will allow organs "hibernate" for days, potentially making organ banking a reality.PMID:39173706 | DOI:10.1016/j.jtcvs.2024.08.015

Neuromuscul Disord. 2024 Aug 2;43:14-19. doi: 10.1016/j.nmd.2024.07.005. Online ahead of print.ABSTRACTMyopathy is a common manifestation in mitochondrial disorders, but the pathomechanisms are still insufficiently studied in children. Here, we report a severe, progressive mitochondrial myopathy in a four-year-old child, who died at eight years. He developed progressive loss of muscle strength with nocturnal hypoventilation and dilated cardiomyopathy. Skeletal muscle showed ragged red fibers and severe combined respiratory chain deficiency. Mitochondrial DNA sequencing revealed a novel m.5670A>G mutation in mitochondrial tRNAAsn (MTTN) with 88 % heteroplasmy in muscle. The proband also had systemic NAD+ deficiency but rescuing this with the NAD+ precursor niacin did not stop disease progression. Targeted metabolomics revealed an overall shift of metabolism towards controls after niacin supplementation, with normalized tryptophan metabolites and lipid-metabolic markers, but most amino acids did not respond to niacin therapy. To conclude, we report a new MTTN mutation, secondary NAD+ deficiency in childhood-onset mitochondrial myopathy with metabolic but meager clinical response to niacin supplementation.PMID:39173541 | DOI:10.1016/j.nmd.2024.07.005

EBioMedicine. 2024 Aug 21;107:105282. doi: 10.1016/j.ebiom.2024.105282. Online ahead of print.ABSTRACTBACKGROUND: Irritable bowel syndrome (IBS) is a common and debilitating disorder manifesting with abdominal pain and bowel dysfunction. A mainstay of treatment is dietary modification, including restriction of FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols). A greater response to a low FODMAP diet has been reported in those with a distinct IBS microbiome termed IBS-P. We investigated whether this is linked to specific changes in the metabolome in IBS-P.METHODS: Solid phase microextraction gas chromatography-mass spectrometry was used to examine the faecal headspace of 56 IBS cases (each paired with a non-IBS household control) at baseline, and after four-weeks of a low FODMAP diet (39 pairs). 50% cases had the IBS-P microbial subtype, while the others had a microbiome that more resembled healthy controls (termed IBS-H). Clinical response to restriction of FODMAPs was measured with the IBS-symptom severity scale, from which a pain sub score was calculated.FINDINGS: Two distinct metabotypes were identified and mapped onto the microbial subtypes. IBS-P was characterised by a fermentative metabolic profile rich in short chain fatty acids (SCFAs). After FODMAP restriction significant reductions in SCFAs were observed in IBS-P. SCFA levels did not change significantly in the IBS-H group. The magnitude of pain and overall symptom improvement were significantly greater in IBS-P compared to IBS-H (p = 0.016 and p = 0.026, respectively). Using just five metabolites, a biomarker model could predict microbial subtype with accuracy (AUROC 0.797, sensitivity 78.6% (95% CI: 0.78-0.94), specificity 71.4% (95% CI: 0.55-0.88).INTERPRETATION: A metabotype high in SCFAs can be manipulated by restricting fermentable carbohydrate, and is associated with an enhanced clinical response to this dietary restriction. This implies that SCFAs harbour pro-nociceptive potential when produced in a specific IBS niche. By ascertaining metabotype, microbial subtype can be predicted with accuracy. This could allow targeted FODMAP restriction in those seemingly primed to respond best.FUNDING: This research was co-funded by Addenbrooke's Charitable Trust, Cambridge University Hospitals and the Wellcome Sanger Institute, and supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014).PMID:39173527 | DOI:10.1016/j.ebiom.2024.105282