PubMed

Nutr Metab (Lond). 2023 Sep 15;20(1):41. doi: 10.1186/s12986-023-00754-z.ABSTRACTBACKGROUND: Dietary intake during early life may be a modifying factor for cardiometabolic risk (CMR). Metabolomic profiling may enable more precise identification of CMR in adolescence than traditional CMR scores. We aim to assess and compare the prospective associations between an obesogenic dietary pattern (DP) score at age 13 years with a novel vs. traditional CMR score in adolescence and young adulthood in the Avon Longitudinal Study of Parents and Children (ALSPAC).METHODS: Study participants were ALSPAC children with diet diary data at age 13. The obesogenic DP z-score, characterized by high energy-density, high % of energy from total fat and free sugars, and low fibre density, was previously derived using reduced rank regression. CMR scores were calculated by combining novel metabolites or traditional risk factors (fat mass index, insulin resistance, mean arterial blood pressure, triacylglycerol, HDL and LDL cholesterol) at age 15 (n = 1808), 17 (n = 1629), and 24 years (n = 1760). Multivariable linear regression models estimated associations of DP z-score with log-transformed CMR z-scores.RESULTS: Compared to the lowest tertile, the highest DP z-score tertile at age 13 was associated with an increase in the metabolomics CMR z-score at age 15 (β = 0.20, 95% CI 0.09, 0.32, p trend < 0.001) and at age 17 (β = 0.22, 95% CI 0.10, 0.34, p trend < 0.001), and with the traditional CMR z-score at age 15 (β = 0.15, 95% CI 0.05, 0.24, p trend 0.020). There was no evidence of an association at age 17 for the traditional CMR z-score (β = 0.07, 95% CI -0.03, 0.16, p trend 0.137) or for both scores at age 24.CONCLUSIONS: An obesogenic DP was associated with greater CMR in adolescents. Stronger associations were observed with a novel metabolite CMR score compared to traditional risk factors. There may be benefits from modifying diet during adolescence for CMR health, which should be prioritized for further research in trials.PMID:37715209 | DOI:10.1186/s12986-023-00754-z

Plant Cell Rep. 2023 Sep 16. doi: 10.1007/s00299-023-03053-2. Online ahead of print.ABSTRACTDose effects of Rf1 gene regulated retrieval mechanism of pollen fertility for CMS-D2 cotton. Cytoplasmic male sterility conditioned by Gossypium harknessii cytoplasm (CMS-D2) is an economical pollination control system for producing hybrid cotton seeds compared to artificial and chemical emasculation methods. However, the unstable restoring ability of restorer lines is a main barrier in the large-scale application of "three-line" hybrid cotton in China. Our phenotypic investigation determined that the homozygous Rf1Rf1 allelic genotype had a stronger ability to generate fertile pollen than the heterozygous Rf1rf1 allelic genotype. To decipher the genetic mechanisms that control the differential levels of pollen fertility, an integrated metabolomic and transcriptomic analysis was performed at two environments using pollen grains of four cotton genotypes differing in Rf1 alleles or cytoplasm. Totally 5,391 differential metabolite features were detected, and 369 specific differential metabolites (DMs) were identified between homozygous and heterozygous Rf1 allelic genotypes with CMS-D2 cytoplasm. In addition, transcriptome analysis identified 2,490 differentially expressed genes (DEGs) and 96 unique hub DEGs with dynamic regulation in this comparative combination. Further integrated analyses revealed that several key DEGs and DMs involved in indole biosynthesis, flavonoid biosynthesis, and sugar metabolism had strong network linkage with fertility restoration. In vitro application of auxin analogue NAA and inhibitor Auxinole confirmed that over-activated auxin signaling might inhibit pollen development, whereas suppressing auxin signaling partially promoted pollen development in CMS-D2 cotton. Our results provide new insight into how the dosage effects of the Rf1 gene regulate pollen fertility of CMS-D2 cotton.PMID:37715064 | DOI:10.1007/s00299-023-03053-2

Sci Rep. 2023 Sep 15;13(1):15280. doi: 10.1038/s41598-023-42293-w.ABSTRACTPulmonary arterial hypertension is a rare but life-threatening and clinically heterogeneous disease. The diagnostic schedule of this disorder is complex, and no specific indicator of the arterial etiology has been explored. In this study, untargeted plasma metabolomics was applied to evaluate the metabolic fingerprints of pulmonary arterial hypertension patients. Plasma samples were prepared using a new approach, which applies proteinase K during the sample preparation procedure to increase the metabolite coverage. The metabolic fingerprints were determined via LC-MS and subsequently analyzed with the use of both uni- and multivariate statistics. A total of 21 metabolites were discovered to be significantly altered in pulmonary arterial hypertensive patients. The metabolites were mainly related to the phospholipid metabolic pathways. In this study, decreases were found in the phosphatidylcholines (PCs) [PC(32:0), PC(40:7), PC(42:7)], phosphatidylethanolamine PE(18:0/18:2), lysophosphatidylethanolamines (LPEs) [LPE(22:6), LPE(18:2), LPE(18:0), LPE(20:4), LPE(20:1), LPE(20:0)], lysophosphatidylcholine LPC(20:4) and lysophosphatidylserine LPS(19:0), as well as increase of sphingomyelin SM(36:2), in the plasma samples of pulmonary arterial hypertensive patients in comparison to the control group. Besides their function as components of the biological membranes, these metabolites are also involved in the intracellular signaling pathways that are related to cell proliferation and apoptosis. The results obtained during this study confirm the potential of (untargeted) metabolomics to identify the molecular characteristics of the pathophysiology of pulmonary arterial hypertension. The clinical relevance of this study constitutes the selection of a metabolic panel that can potentially detect and properly diagnose the disease.PMID:37714912 | DOI:10.1038/s41598-023-42293-w

Nat Commun. 2023 Sep 15;14(1):5728. doi: 10.1038/s41467-023-41462-9.ABSTRACTArachidonic and adrenic acids in the membrane play key roles in ferroptosis. Here, we reveal that lipoprotein-associated phospholipase A2 (Lp-PLA2) controls intracellular phospholipid metabolism and contributes to ferroptosis resistance. A metabolic drug screen reveals that darapladib, an inhibitor of Lp-PLA2, synergistically induces ferroptosis in the presence of GPX4 inhibitors. We show that darapladib is able to enhance ferroptosis under lipoprotein-deficient or serum-free conditions. Furthermore, we find that Lp-PLA2 is located in the membrane and cytoplasm and suppresses ferroptosis, suggesting a critical role for intracellular Lp-PLA2. Lipidomic analyses show that darapladib treatment or deletion of PLA2G7, which encodes Lp-PLA2, generally enriches phosphatidylethanolamine species and reduces lysophosphatidylethanolamine species. Moreover, combination treatment of darapladib with the GPX4 inhibitor PACMA31 efficiently inhibits tumour growth in a xenograft model. Our study suggests that inhibition of Lp-PLA2 is a potential therapeutic strategy to enhance ferroptosis in cancer treatment.PMID:37714840 | DOI:10.1038/s41467-023-41462-9

J Autoimmun. 2023 Sep 13:103108. doi: 10.1016/j.jaut.2023.103108. Online ahead of print.ABSTRACTThe role of gut microbiome and metabolic substances in the development of autoimmune diseases has gradually been revealed. However, the relevant gut features in pemphigus have not been well clarified. We collected stool samples from pemphigus patients and healthy controls (HCs). Metagenomic sequencing and liquid chromatography-mass spectrometry (LC/MS) metabolome sequencing were performed to analyze the compositional and metabolic alternations of the gut microbiome in pemphigus patients and HCs. We observed the reduced richness and diversity and greater heterogeneity in pemphigus patients, which was characterized by a significant decrease in Firmicutes and an increase in Proteobacteria. At the species level, Intestinal pathogenic bacteria such as Escherichia coli and Bacteroides fragilis were significantly enriched, while anti-inflammatory bacteria and butyric acid-producing bacteria were significantly reduced, which were related to clinical indicators (Dsg1/3 and PDAI). 4 species were selected by the machine learning algorithm to better distinguish pemphigus patients from healthy people. Metabolomic analysis showed that the composition of pemphigus patients was different from that of HCs. PE (18:3 (6Z,9Z, 12Z)/14:1 (9Z)) was the main metabolic substance in pemphigus and involved in a variety of metabolic pathways. While Retinol, flavonoid compounds and various amino acids decreased significantly compared with HCs. Furthermore, we found that differences in the levels of these metabolites correlated with changes in the abundance of specific species. Our study provides a comprehensive picture of gut microbiota and metabolites in pemphigus patients and suggests a potential mechanism of the aberrant gut microbiota and metabolites in the pathogenesis of pemphigus.PMID:37714737 | DOI:10.1016/j.jaut.2023.103108

J Mol Cell Cardiol. 2023 Sep 13:S0022-2828(23)00140-2. doi: 10.1016/j.yjmcc.2023.09.001. Online ahead of print.ABSTRACTObesity and metabolic disorders are increasing in epidemic proportions, leading to poor outcomes including heart failure. With a growing recognition of the effect of adipose tissue dysfunction on heart disease, it is less well understood how the heart can influence systemic metabolic homeostasis. Even less well understood is sex differences in cardiometabolic responses. Previously, our lab investigated the role of the amino-terminus of GRK2 in cardiometabolic remodeling using transgenic mice with cardiac restricted expression of a short peptide, βARKnt. Male mice preserved insulin sensitivity, enhanced metabolic flexibility and adipose tissue health, elicited cardioprotection, and improved cardiac metabolic signaling. To examine the effect of cardiac βARKnt expression on cardiac and metabolic function in females in response to diet-induced obesity, we subjected female mice to high fat diet (HFD) to trigger cardiac and metabolic adaptive changes. Despite equivalent weight gain, βARKnt mice exhibited improved glucose tolerance and insulin sensitivity. However, βARKnt mice displayed a progressive reduction in energy expenditure during cold challenge after acute and chronic HFD stress. They also demonstrated reduced cardiac function and increased markers of maladaptive remodeling and tissue injury, and decreased or aberrant metabolic signaling. βARKnt mice exhibited reduced lipid deposition in the brown adipose tissue (BAT), but delayed or decreased markers of BAT activation and function suggested multiple mechanisms contributed to the decreased thermogenic capacity. These data suggest a non-canonical cardiac regulation of BAT lipolysis and function that highlights the need for studies elucidating the mechanisms of sex-specific responses to metabolic dysfunction.PMID:37714510 | DOI:10.1016/j.yjmcc.2023.09.001

Chemosphere. 2023 Sep 13:140108. doi: 10.1016/j.chemosphere.2023.140108. Online ahead of print.ABSTRACTNanoplastics have been widely studied as environmental pollutants, which can accumulate in the human body through the food chain or direct contact. Research has shown that nanoplastics can affect the immune system and mitochondrial function, but the underlying mechanisms are unclear. Lungs and macrophages have important immune and metabolic functions. This study explored the effects of 100 nm PS-NPs on innate immunity, mitochondrial function, and cellular metabolism-related pathways in lung (BEAS-2B) cells and macrophages (RAW264.7). The results had shown that PS-NPs exposure caused a decrease in mitochondrial membrane potential, intracellular ROS accumulation, and Ca2+ overload, and activated the cGAS-STING signaling pathway related to innate immunity. These changes had been observed at concentrations of PS-NPs as low as 60 μg/mL, which might have been comparable to environmental levels. Non-target metabolomics and Western Blotting results confirmed that PS-NPs regulated prostaglandin B1 and other metabolites to cause cell damage through the cGAS-STING pathway. Supplementation of prostaglandin B1 alleviated the immune activation and metabolic disturbance caused by PS-NPs exposure. This study identified PS-NPs-induced innate immune activation, mitochondrial dysfunction, and metabolic toxicity pathways, providing new insights into the potential for adverse outcomes of NPs in human life.PMID:37714480 | DOI:10.1016/j.chemosphere.2023.140108

Sci Total Environ. 2023 Sep 13:167079. doi: 10.1016/j.scitotenv.2023.167079. Online ahead of print.ABSTRACTIn wild animals, diet and gut microbiota interactions are critical moderators of metabolic functions and are highly contingent on habitat conditions. Challenged by the extreme conditions of high-altitude environments, the strategies implemented by highland animals to adjust their diet and gut microbial composition and modulate their metabolic substrates remain largely unexplored. By employing a typical human commensal species, the Eurasian tree sparrow (Passer montanus, ETS), as a model species, we studied the differences in diet, digestive tract morphology and enzyme activity, gut microbiota, and metabolic energy profiling between highland (the Qinghai-Tibet Plateau, QTP; 3230 m) and lowland (Shijiazhuang, Hebei; 80 m) populations. Our results showed that highland ETSs had enlarged digestive organs and longer small intestinal villi, while no differences in key digestive enzyme activities were observed between the two populations. The 18S rRNA sequencing results revealed that the dietary composition and abundance of highland ETSs were more animal-based and less plant-based than those of the lowland ones. Furthermore, 16S rRNA sequencing results suggested that the intestinal microbial communities were structurally segregated between populations. PICRUSt metagenome predictions further indicated that the expression patterns of microbial genes involved in material and energy metabolism, immune system and infection, and xenobiotic biodegradation were strikingly different between the two populations. Analysis of liver metabolomics revealed significant metabolic differences between highland and lowland ETSs in terms of substrate utilization, as well as distinct sex-specific alterations in glycerophospholipids. Furthermore, the interplay between diet, liver metabolism, and gut microbiota suggests a dietary shift resulting in corresponding changes in gut microbiota and metabolic functions. Our findings indicate that highland ETSs have evolved to optimize digestion and absorption, rely on more protein-rich foods, and possess gut microbiota tailored to their dietary composition, likely adaptive physiological and ecological strategies adopted to cope with extreme highland environments.PMID:37714349 | DOI:10.1016/j.scitotenv.2023.167079

Sci Total Environ. 2023 Sep 13:167071. doi: 10.1016/j.scitotenv.2023.167071. Online ahead of print.ABSTRACTMicro/nanoplastics (M/NPs) and phthalates (PAEs) are emerging pollutants. Polystyrene (PS) MPs and dibutyl phthalate (DBP) are typical MPs and PAEs in the environment. However, how dandelion plants respond to the combined contamination of MPs and PAEs remains unclear. In this study, we evaluated the individual and combined effects of PS NPs (10 mg L-1) and DBP (50 mg L-1) on dandelion (Taraxacum officinale) seedlings. The results showed that compared to control and individual-treated plants, coexposure to PS NPs and DBP significantly affected plant growth, induced oxidative stress, and altered enzymatic and nonenzymatic antioxidant levels of dandelion. Similarly, photosynthetic attributes and chlorophyll fluorescence kinetic parameters were significantly affected by coexposure. Scanning electron microscopy (SEM) results showed that PS particles had accumulated in the root cortex of the dandelion. Metabolic analysis of dandelion showed that single and combined exposures caused the plant's metabolic pathways to be profoundly reprogrammed. As a consequence, the synthesis and energy metabolism of carbohydrates, amino acids, and organic acids were affected because galactose metabolism, the citric acid cycle, and alanine, aspartic acid and glutamic acid metabolism pathways were significantly altered. These results provide a new perspective on the phytotoxicity and environmental risk assessment of MPs and PAEs in individual or coexposures.PMID:37714347 | DOI:10.1016/j.scitotenv.2023.167071

Sci Total Environ. 2023 Sep 13:167016. doi: 10.1016/j.scitotenv.2023.167016. Online ahead of print.ABSTRACTModerate altitude exposure has shown beneficial effects on diabetes incidence but the underlying mechanisms are not understood. Our study aimed to investigate how the human gut microbiome impacted the serum metabolome and associated with glucose homeostasis in healthy Chinese individuals upon moderate-altitude exposure. Faecal microbiome composition was assessed using shotgun metagenomic sequencing. Serum metabolome was acquired by untargeted metabolomics technology, and amino acids (AAs) and propionic acid in serum were quantified by targeted metabolomics technology. The results indicated that the moderate-altitude exposed individuals presented lowered fasting blood glucose (FBG) and propionic acid, increased circulating l-Glutamine but decreased L-Glutamate and L-Valine, which correlated with enriched Bacteroidetes and decreased Proteobacteria. Additionally, the silico causality associations among gut microbiota, serum metabolome and host FBG were analyzed by mediation analysis. It showed that increased Bacteroides ovatus (B. ovatus) and decreased Escherichia coli (E. coli) were identified as the main antagonistic species driving the association between L-Glutamate and FBG in silico causality. Furthermore, the high-fat diet (HFD) fed mice subjected to faecal microbiota transplantation (FMT) were applied to validate the cause-in-fact effects of gut microbiota on the beneficial glucose response. We found that microbiome in the moderate-altitude exposed donor could predict the extent of the FBG response in recipient mice, which showed lowered FBG, L-Glutamate and Firmicutes/Bacteroidetes ratio. Our findings suggest that moderate-altitude exposure targeting gut microbiota and circulating metabolome, may pave novel avenues to counter dysglycemia.PMID:37714338 | DOI:10.1016/j.scitotenv.2023.167016

Int J Biol Macromol. 2023 Sep 13:126861. doi: 10.1016/j.ijbiomac.2023.126861. Online ahead of print.ABSTRACTBioactive polysaccharides known as the biological response modifiers, can directly interact with intestinal epithelium cells (IEC) and regulate key metabolic processes such as lipid metabolism. Here, the coculture of Caco-2/HT29 monolayer (>400 Ω × cm2) and HepG2 cells was developed to mimic the gut-liver interactions. This system was used to investigate the effects of raw and fermented barley β-glucans (RBG and FBG) on lipid metabolism by directly interacting with IEC. Both RBG and FBG significantly and consistently reduced the lipid droplets and triacylglycerol levels in monoculture and coculture of HepG2 overloaded with oleic acid. Notably, FBG significantly and distinctly elevated PPARα (p < 0.05) and PPARα-responsive ACOX-1 (p < 0.01) gene expressions, promoting lipid degradation in cocultured HepG2. Moreover, the metabolomics analyses revealed that FBG had a unique impact on extracellular metabolites, among them, the differential metabolite thiomorpholine 3-carboxylate was significantly and strongly correlated with PPARα (r = -0.68, p < 0.01) and ACOX-1 (r = -0.76, p < 0.01) expression levels. Taken together, our findings suggest that FBG-mediated gut-liver interactions play a key role in its lipid-lowering effects that are superior to those of RBG. These results support the application of Lactiplantibacillus fermentation for improving hypolipidemic outcomes.PMID:37714241 | DOI:10.1016/j.ijbiomac.2023.126861

J Ethnopharmacol. 2023 Sep 13:117182. doi: 10.1016/j.jep.2023.117182. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Parkinson's disease (PD) is a rapidly progressing neurological disorder. Currently, Medication for PD has numerous limitations. Baichanting Compound (BCT) is a Chinese herbal prescription, a Combination of Acanthopanax senticosus (Rupr. and Maxim.) Harms, Paeonia lactiflora Pall and Uncaria rhynchophylla (Miq.) Miq. ex Havil, that was developed to treat PD and holds a national patent (ZL, 201110260536.3).AIM OF THE STUDY: To clarify the therapeutic effect of BCT on PD and explore its possible mechanism based on metabolomics and metagenomics.MATERIALS AND METHODS: C57BL/6 mice were used as a control group, and α-syn transgenic C57BL/6 mice were randomly assigned to the PD (without treatment) or BCT (with BCT treatment) group. UPLC-MS was performed to detect dopamine levels in brain tissue, while ELISA was used to determine inflammatory factors such as IL-1β, IL-6, TNF-α, IFN-γ and NO, and oxidative stress indicators such as malondialdehyde, superoxide dismutase and glutathione peroxidase enzyme activity. Fecal metabolomics was used to detect fecal metabolic profiles, screen differential metabolic markers, and predict metabolic pathways by KEGG enrichment analysis. Metagenomics was used to determine the intestinal microbial composition, and KO enrichment analysis was performed to predict the potential function of different gut microbiota. Finally, Spearman correlation analysis was used to find the possible relationships among intestinal flora, metabolic markers, inflammatory factors, oxidative stress and dopamine levels.RESULTS: BCT increased the superoxide dismutase activity of α-Syn transgenic C57BL/6 mice (P < 0.01), decreased the levels of TNF-α, IFN-γ, IL-1β, IL-6, NO and malondialdehyde (P < 0.01, 0.05), and increased the release of dopamine (P < 0.01). Metabolomics results show that BCT could regulate Acetatifactor, Marvinbryantia, Faecalitalea, Anaeromassilibacillus, Anaerobium, Pseudobutyrivibrio and Lachnotalea and Acetatifactor_muris, Marvinbryantia_formatexigens, Lachnotalea_sp_AF33_28, Faecalitalea_sp_Marseille_P3755 and Anaerobium_acetethylicum, Gemmiger_sp_An120 abundance to restore intestinal flora function, and reverse fecal metabolism trend, restoring the content of α-D-glucose, cytidine, L-glutamate, L-glutamine, N-acetyl-L-glutamate, raffinose and uracil. In addition, it regulates arginine biosynthesis, D-glutamine and D-glutamate, pyrimidine, galactose and alanine, aspartate and glutamate metabolic pathways.CONCLUSION: BCT may regulate the composition of the gut microbiota to reverse fecal metabolism in PD mice to protect the substantia nigra and striatum from oxidative stress and inflammatory factors and ultimately play an anti-PD role.PMID:37714224 | DOI:10.1016/j.jep.2023.117182

Medicina (B Aires). 2023 Sep;83 Suppl 4:3-8.ABSTRACTThe advances in the field of inborn errors of metabolism (IEM) are spectacular. New IEM have been described, their pathophysiological bases and implications for the organism are better known. With the advent of new metabolomics, lipidomics and genomics techniques, advances in diagnosis have multiplied and allow new therapeutic options to be explored. A new IEM classification has been established based on the more than 1.450 IEM identified. A new specialty is emerging, which is metabolic medicine. Neonatal screening is becoming universal and allows us today, with tandem mass, to diagnose more than 20 metabolic diseases of the neonatal period, with treatment options. IEM units for adults are being created to follow-up children with IEM who survive the disease and with an increasingly better quality of life, and some IEM that start in adolescence or adulthood are diagnosed. Personalized therapies and clinical practice guidelines appear for any IEM. Finally, new therapeutic options are emerging day to day that allow a longer survival and better quality of life. Conventional gene therapy is already being applied in some IEM. However, gene editing strategies with RNA therapies may allow the correction of the genetic mutation, minimizing the problems associated with conventional compensation gene therapy.PMID:37714115

Biochim Biophys Acta Mol Basis Dis. 2023 Sep 13;1870(1):166876. doi: 10.1016/j.bbadis.2023.166876. Online ahead of print.ABSTRACTBACKGROUND: Studies have found that the plasma content of gut-derived 4-hydroxyphenylacetic acid (4-HPA) was significantly increased in septic patients. However, the mechanism of 4-HPA elevation during sepsis and its relationship with sepsis-induced acute kidney injury (SAKI) remain unclear.METHODS: Cecal ligation and puncture (CLP) was performed in C57BL/6 mice to establish the SAKI animal model. Human renal tubular epithelial (HK-2) cells stimulated with lipopolysaccharide were used to establish the SAKI cell model. The widely targeted metabolomics was applied to analyze the renal metabolite changes after CLP. Proteomics was used to explore potential target proteins regulated by 4-HPA. The blood sample of clinical sepsis patients was collected to examine the 4-HPA content.RESULTS: We found that renal gut-derived 4-HPA levels were significantly increased after CLP. The high permeability of intestinal barrier after sepsis contributed to the dramatic increase of renal 4-HPA. Intriguingly, we demonstrated that exogenous 4-HPA administration could further significantly reduce CLP-induced increases in serum creatinine, urea nitrogen, and cystatin C, inhibit renal pathological damage and apoptosis, and improve the survival of mice. Mechanistically, 4-HPA inhibited necroptosis in renal tubular epithelial cells by upregulating the protein expression of apoptosis repressor with caspase recruitment domain (ARC) and enhancing the interaction between ARC and receptor-interacting protein kinase 1 (RIPK1).CONCLUSIONS: The increase of gut-derived 4-HPA in the kidney after sepsis could play a protective effect in SAKI by upregulating ARC to inhibit necroptosis.PMID:37714058 | DOI:10.1016/j.bbadis.2023.166876

Ecotoxicol Environ Saf. 2023 Sep 13;264:115463. doi: 10.1016/j.ecoenv.2023.115463. Online ahead of print.ABSTRACTPolymer materials have great potential for soil heavy metal contamination remediation, but the metabolic mechanism by which polymer amendments regulate the responses of soil-plant systems to cadmium (Cd) stress is still unclear. To clarify the metabolic mechanism by which a self-developed soluble polymer amendment (PA) remediates Cd contamination in cotton fields, the common and differential metabolites in soil and cotton leaves were analyzed during the critical period of cotton growth (flowering and bolling stage) in a field experiment. The results showed that Cd stress increased Cd concentration in the soil-cotton system, and reduced enzyme activity in soil and cotton leaves. Besides, Cd stress also reduced the abundance of α-linolenic acid in soil and the abundance of 2-Oxoarginine and S-Adenosylmethionine in cotton leaves. These ultimately led to reductions in weight, boll number, yield, and fiber elongation. However, the application of PA to the Cd-contaminated soil significantly reduced the soil exchangeable Cd (Ex-Cd) concentration by 41.43%, and increased the boll number, yield, and fiber strength by 14.17%, 21.04%, and 19.89%, respectively compared with the Cd treatment. The results of metabolomic analysis showed that PA application mainly affected the Nicotinate and nicotinamide metabolism pathway, Lysine degradation pathway, and Arginine and proline metabolism pathway in cotton leaves and soil. Besides, in these metabolic pathways, succinic acid semialdehyde of cotton leaves, saccharopine of soil, and S-Adenosylmethionine of soil and cotton had the most significant response to PA application. Therefore, the application of PA to Cd-contaminated soil can increase soil and cotton leaf enzyme activity and cotton yield (boll number and seed cotton yield) and quality (fiber strength), and maintain soil-plant material balance by regulating the distribution of Cd ions and key metabolites in the soil-cotton system. This study will deepen our understanding of the metabolic mechanism of PA remediating Cd-contaminated cotton fields, and provide a technical reference for the remediation of heavy metal contamination in drip-irrigated cotton fields in arid areas.PMID:37714036 | DOI:10.1016/j.ecoenv.2023.115463

Ecotoxicol Environ Saf. 2023 Sep 13;264:115456. doi: 10.1016/j.ecoenv.2023.115456. Online ahead of print.ABSTRACTExposure to particulate matter (PM) from agricultural environments has been extensively reported to cause respiratory health concerns in both animals and agricultural workers. Furthermore, PM from agricultural environments, containing fungal spores, has emerged as a significant threat to public health and the environment. Despite its potential toxicity, the impact of fungal spores present in PM from agricultural environments on the lung microbiome and metabolic profile is not well understood. To address this gap in knowledge, we developed a mice model of immunodeficiency using cyclophosphamide and subsequently exposed the mice to fungal spores via the trachea. By utilizing metabolomics techniques and 16 S rRNA sequencing, we conducted a comprehensive investigation into the alterations in the lung microbiome and metabolic profile of mice exposed to fungal spores. Our study uncovered significant modifications in both the lung microbiome and metabolic profile post-exposure to fungal spores. Additionally, fungal spore exposure elicited noticeable changes in α and β diversity, with these microorganisms being closely associated with inflammatory factors. Employing non-targeted metabolomics analysis via GC-TOF-MS, a total of 215 metabolites were identified, among which 42 exhibited significant differences. These metabolites are linked to various metabolic pathways, with amino sugar and nucleotide sugar metabolism, as well as galactose metabolism, standing out as the most notable pathways. Cysteine and methionine metabolism, along with glycine, serine and threonine metabolism, emerged as particularly crucial pathways. Moreover, these metabolites demonstrated a strong correlation with inflammatory factors and exhibited significant associations with microbial production. Overall, our findings suggest that disruptions to the microbiome and metabolome may hold substantial relevance in the mechanism underlying fungal spore-induced lung damage in mice.PMID:37714035 | DOI:10.1016/j.ecoenv.2023.115456

Biomed Pharmacother. 2023 Sep 13;167:115487. doi: 10.1016/j.biopha.2023.115487. Online ahead of print.ABSTRACTItaconic acid (IA), a metabolite generated by the tricarboxylic acid (TCA) cycle in eukaryotic immune cells, and its derivative dimethyl itaconate (DI) exert antibacterial functions in intracellular environments. Previous studies suggested that IA and DI only inhibit bacterial growth in carbon-limited environments; however, whether IA and DI maintain antibacterial activity in carbon-enriched environments remains unknown. Here, IA and DI inhibited the bacteria with minimum inhibitory concentrations of 24.02 mM and 39.52 mM, respectively, in a carbon-enriched environment. The reduced bacterial pathogenicity was reflected in cell membrane integrity, motility, biofilm formation, AI-2/luxS, and virulence. Mechanistically, succinate dehydrogenase (SDH) activity and fumaric acid levels decreased in the IA and DI treatments, while isocitrate lyase (ICL) activity was upregulated. Inhibited TCA circulation was also observed through untargeted metabolomics. In addition, energy-related aspartate metabolism and lysine degradation were suppressed. In summary, these results indicated that IA and DI reduced bacterial pathogenicity while exerting antibacterial functions by inhibiting TCA circulation. This study enriches knowledge on the inhibition of bacteria by IA and DI in a carbon-mixed environment, suggesting an alternative method for treating bacterial infections by immune metabolites.PMID:37713987 | DOI:10.1016/j.biopha.2023.115487

EBioMedicine. 2023 Sep 13;96:104798. doi: 10.1016/j.ebiom.2023.104798. Online ahead of print.ABSTRACTBACKGROUND: Asthenozoospermia is the primary cause of male infertility; however, its genetic aetiology remains poorly understood. Adenylate kinase 9 (AK9) is highly expressed in the testes of humans and mice and encodes a type of adenosine kinase that is functionally involved in cellular nucleotide homeostasis and energy metabolism. We aimed to assess whether AK9 is involved in asthenozoospermia.METHODS: One-hundred-and-sixty-five Chinese men with idiopathic asthenozoospermia were recruited. Whole-exome sequencing (WES) and Sanger sequencing were performed for genetic analyses. Papanicolaou staining, Haematoxylin and eosin staining, scanning electron microscopy, and transmission electron microscopy were used to observe the sperm morphology and structure. Ak9-knockout mice were generated using CRISPR-Cas9. Sperm adenosine was detected by liquid chromatography-mass spectrometry. Targeted sperm metabolomics was performed. Intracytoplasmic sperm injection (ICSI) was used to treat patients.FINDINGS: We identified five patients harbouring bi-allelic AK9 mutations. Spermatozoa from men harbouring bi-allelic AK9 mutations have a decreased ability to sustain nucleotide homeostasis. Moreover, bi-allelic AK9 mutations inhibit glycolysis in sperm. Ak9-knockout male mice also presented similar phenotypes of asthenozoospermia. Interestingly, ICSI was effective in bi-allelic AK9 mutant patients in achieving good pregnancy outcomes.INTERPRETATION: Defects in AK9 induce asthenozoospermia with defects in nucleotide homeostasis and energy metabolism. This sterile phenotype could be rescued by ICSI.FUNDING: The National Natural Science Foundation of China (82071697), Medical Innovation Project of Fujian Province (2020-CXB-051), open project of the NHC Key Laboratory of Male Reproduction and Genetics in Guangzhou (KF202004), Medical Research Foundation of Guangdong Province (A2021269), Guangdong Provincial Reproductive Science Institute Innovation Team grants (C-03), and Outstanding Young Talents Program of Capital Medical University (B2205).PMID:37713809 | DOI:10.1016/j.ebiom.2023.104798

Poult Sci. 2023 Aug 18;102(11):103020. doi: 10.1016/j.psj.2023.103020. Online ahead of print.ABSTRACTLiancheng white duck is a typical local duck breed in Fujian Province famous for its meat traits. To better understand how meat quality varies with breed, the chemical composition of breast meats of Liancheng white ducks (LD) and Cherry Valley ducks (CD) were examined using ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS).The correlation between meat quality and the differential metabolites was further analyzed. The results showed that the effects of breed on duck breast meat were significant for pH, color, cooking loss, and shear force. Liancheng white duck breast meat exhibited a higher shear force and pH, and lower cooking loss and lightness (L*24), redness (a*24), and yellowness (b*24) than CD. Metabolomic analysis revealed significant differences between the meat extracts from the 2 duck breeds. A total of 49 and 57 significantly different metabolites were identified in positive and negative ion modes, respectively. These differentially accumulated metabolites (DAMs) could be divided into 28 classes, of which the 4 main categories were carbohydrates, amino acids, fatty acids, and eicosanoids. Liancheng white duck might have better nutritional and medicinal value considering the higher content of (4Z,7Z,10Z,13Z,16Z,19Z)-4,7,10,13,16,19-docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), eicosapentaenoic acid (EPA), and prostaglandinF3α (PGF3α), having anti-inflammatory orantioxidant effects. Carbohydrate concentration negatively correlated with pH24. The 4 metabolites positively correlated with the shear force. These results provide an overall perspective for bridging the gap between variation of duck meat quality and metabolites with respect to breed.PMID:37713801 | DOI:10.1016/j.psj.2023.103020

Int Immunopharmacol. 2023 Sep 13;124(Pt A):110885. doi: 10.1016/j.intimp.2023.110885. Online ahead of print.ABSTRACTRecent studies suggested that altered gut microbiota may be related to the pathogenesis of rheumatoid arthritis (RA), albeit the exact mechanisms are unknown. In this study, we aimed to discover the particular mechanism of RA treatment by microbiota by investigating the effects of ferroptosis on gut microbiota and its metabolites in collagen-induced arthritis (CIA) mice. Mice were divided into five groups: control, CIA, erastin, BzATP, and BzATP + erastin group. We performed 16S rDNA sequencing and metabolomics analysis on mouse feces and found that erastin and BzATP altered the microbiota and metabolites. The findings demonstrated that the microbiota was significantly disturbed at the phylum (Proteobacteria, Firmicutes, and Bacteroidota) and genus level (Lachnospiraceae_NK4A136, Lactobacillus, and Bifidobacterium) in the CIA group, and erastin exacerbated this disturbance. Unexpectedly, BzATP treatment could repair the disruptive effects of erastin. Additionally, there were significant variations in metabolites between each group. Erastin worsened metabolite abnormalities in CIA mice, while BzATP mitigated them, consistent with the microbiota results. These findings provide novel perspectives and insights into the therapy of RA.PMID:37713784 | DOI:10.1016/j.intimp.2023.110885