PubMed

Comp Biochem Physiol C Toxicol Pharmacol. 2024 Oct 25:110062. doi: 10.1016/j.cbpc.2024.110062. Online ahead of print.ABSTRACTThe increasing release of tire-derived particles, particularly those containing N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), into the environment has raised concerns regarding their ecological impact. This study aims to elucidate the toxicological effects of 6PPD on the metabolism in early developmental stage of zebrafish. Larval zebrafish were exposed to 10 and 100 μg/L 6PPD, and some endpoints in biochemical parameters, gene expression, and metabolism were analyzed. The results showed that 6PPD exposure disrupted glucolipid metabolism in zebrafish larvae, evidenced by increased triglyceride (TG) levels and decreased glucose content. Nile red staining indicated significant lipid accumulation in the liver and intestines. Additionally, RT-qPCR analysis revealed the upregulation of genes involved in lipid synthesis and metabolism, such as ppar-γ and fas, and downregulation of glycolysis-related genes like pk and gk. Furthermore, the untargeted metabolomics technique was used to identify a total of 220 differentially expressed metabolites (DEMs) with changes in amino acid metabolism, lipid metabolism, and the TCA cycle. KEGG pathway enrichment analysis highlighted disruptions mainly in Taurine and hypotaurine metabolism, Arginine and proline metabolism, and Histidine metabolism, which played very important roles on energy metabolism in zebrafish. The results provided some critical insights into the ecological risks associated with 6PPD.PMID:39490946 | DOI:10.1016/j.cbpc.2024.110062

Int J Biol Macromol. 2024 Oct 25:136930. doi: 10.1016/j.ijbiomac.2024.136930. Online ahead of print.ABSTRACTFucoidan has attracted significant attention owing to its remarkable bioactivities, but the effect of molecular weight (Mw) on its activities in the context of alcoholic liver diseases (ALD) is poorly understood. In this study, low Mw fucoidan (OSLF) was prepared, and its protective effect against alcohol-induced liver injury was assessed in a mouse model. OSLF increased weight gain and colon length, improved lipid disorders, and reduced oxidative stress in mice exposed to alcohol, alleviating liver injury. OSLF alleviated inflammation in the liver by inhibiting alcohol-activated NF-κB and MAPK pathways. The underlying mechanism can be attributed to the improvement of alcohol-induced dysbiosis of the gut microbiota, including a decrease in Proteobacteria and Bacteroidetes and an increase in microbiota diversity, as well as the abundances of Parabacteroides, Bacteroides, and Faecalibaculum. Metabolomics results showed that OSLF improved alcohol-induced abnormalities of microbiota metabolites, primarily involving amino acid metabolism and short chain fatty acids production. In addition, OSLF ameliorated bile acid metabolism in the gut and regulated the expression of bile acid-associated genes in the liver, affecting bile acid synthesis, regulation, and transport. It suggested that OSLF had the potential for the management of ALD by regulating the gut microbiota-bile acid-liver axis.PMID:39490864 | DOI:10.1016/j.ijbiomac.2024.136930

Int J Pharm. 2024 Oct 26:124874. doi: 10.1016/j.ijpharm.2024.124874. Online ahead of print.ABSTRACTCo-crystallization of a therapeutic ingredient with an appropriate co-former is a powerful technique to augment the physicochemical and pharmacokinetic properties and the effectiveness of Active Pharmaceutical Ingredients (APIs). Biochanin A (BCA), a flavonoid with medicinal potential, is limited by poor solubility and low oral bioavailability. This study aimed to design and develop a novel BCA-nicotinamide cocrystal as BCC to enhance BCA's oral bioavailability and explore its therapeutic potential for ameliorating cerulein-induced acute pancreatitis (CIAP) by elucidating the target identification utilizing tissue/serum metabolite profiles. The cocrystal was designed by the supramolecular synthon approach and characterized by single-crystal X-ray diffraction that confirms a robust three-dimensional hydrogen-bonded network of BCA and Nicotinamide (NCT) in the crystal. FT-IR and DSC were used to analyze the cocrystal's intermolecular interactions and thermal behavior. BCC exhibited enhanced solubility and drug release compared to BCA alone, resulting in enhanced oral bioavailability and pancreatic tissue concentration. Comparing BCC to BCA in the CIAP model, BCC therapy remarkably reduced cerulein-induced pancreatitis, evidenced by significant reductions in inflammation, acinar cell atrophy, and amylase levels in pancreatic tissues. Further, the cocrystal formulation also down-regulated the oxidative stress markers, inflammatory cytokines and macrophage-related proteins. The study has identified distinct metabolomic signatures linked with AP with the help of Orbitrap Exploris mass spectrometry, which could pave the way for creating focused diagnostic tools for a better prognosis. In conclusion, these results offer new insights into exploring mechanistic pathways associated with specific biomarkers and underscore BCC cocrystals as a promising approach to enhance BCA's therapeutic potential.PMID:39490549 | DOI:10.1016/j.ijpharm.2024.124874

J Ethnopharmacol. 2024 Oct 26:118999. doi: 10.1016/j.jep.2024.118999. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria baicalensis Georgi, a widely used Chinese medicinal herb, has shown effectiveness against lung cancer. Scutellarein, a key component of Scutellaria baicalensis, also demonstrates anticancer properties in lung cancer. However, the underlying mechanisms have not yet been clarified.AIM OF THE STUDY: This study aimed to investigate the effects of scutellarein in the treatment of NSCLC and its underlying mechanisms.METHODS: This study explored the effects of scutellarein on non-small cell lung cancer (NSCLC) and its mechanisms. A Lewis lung cancer mouse model was established to assess scutellarein's anticancer activity in vivo. Additionally, the compound's effects on cell proliferation, colony formation, migration, and apoptosis were evaluated in vitro using A549 and H1299 lung cancer cells. Metabolomics analysis was conducted to identify changes in cellular metabolism due to scutellarein, while molecular docking and western blotting techniques were employed to elucidate the molecular mechanisms of its anti-lung cancer effects.RESULTS: Scutellarein significantly inhibited lung cancer xenograft tumor growth. In vitro studies showed that scutellarein suppressed migration and colony formation in A549 and H1299 cells, induced cell cycle arrest, and triggered cell apoptosis. Notably, scutellarein profoundly altered amino acid metabolism, particularly affecting glutamine metabolites. It affected key glutamine transporters ASCT2 and LAT1, as well as glutaminase GLS1, leading to their reduced expression.CONCLUSION: Scutellarein effectively inhibits lung cancer growth both in vivo and in vitro by inducing cell apoptosis and downregulating the glutamine metabolic pathway.PMID:39490431 | DOI:10.1016/j.jep.2024.118999

Biomater Adv. 2024 Oct 23;166:214085. doi: 10.1016/j.bioadv.2024.214085. Online ahead of print.ABSTRACTThis study reports on the metabolic changes accompanying the differentiation of MC3T3-E1 osteoprogenitor cells induced by mesoporous bioactive glass nanospheres (nMBG) loaded with ipriflavone (nMBG-IP). Ipriflavone (IP) is a synthetic isoflavone known for inhibiting bone resorption, maintaining bone density, and preventing osteoporosis. Delivering IP intracellularly is a promising strategy to modulate bone remodeling at significantly lower doses compared to free drug administration. Our results demonstrate that nMBG are efficiently internalized by pre-osteoblasts and, when loaded with IP, induce their differentiation. This differentiation process is accompanied by pronounced metabolic alterations, as monitored by NMR analysis of medium supernatants and cell extracts (exo- and endo-metabolomics, respectively). The main effects include an early-stage intensification of glycolysis and changes in several metabolic pathways, such as nucleobase metabolism, osmoregulatory and antioxidant pathways, and lipid metabolism. Notably, the metabolic impacts of nMBG-IP and free IP were very similar, whereas nMBG alone induced only mild changes in the intracellular metabolic profile without affecting the cells' consumption/secretion patterns or lipid composition. This finding indicates that the observed effects are primarily related to IP-induced differentiation and that nMBG nanospheres serve as convenient carriers with both efficient internalization and minimal metabolic impact. Furthermore, the observed link between pre-osteoblast differentiation and metabolism underscores the potential of utilizing metabolites and metabolic reprogramming as strategies to modulate the osteogenic process, for instance, in the context of osteoporosis and other bone diseases.PMID:39490191 | DOI:10.1016/j.bioadv.2024.214085

J Hazard Mater. 2024 Oct 22;480:136229. doi: 10.1016/j.jhazmat.2024.136229. Online ahead of print.ABSTRACTThe use of algaecides to control high-density cyanobacterial blooms is often complicated by secondary pollution and the toxicity to non-target organisms. This study investigates the individual and combined effects of sodium dichloroisocyanurate (NaDCC, 5, 50, and 100 mg/L) and isothiazolinone (0.1, 0.5, and 1.5 mg/L) on a cyanobacteria-Vallisneria natans-microbe aquatic ecosystem, focusing on their interactions and ecological impacts. Results indicate that NaDCC could achieve a higher algae removal rate than isothiazolinone within 15 days, but has a greater negative effect on Vallisneria natans. Both algaecides disrupt nutrient and secondary metabolite balances at low and high concentrations, increasing nutrient loads and harmful substances. Optimal results were obtained with low concentrations of NaDCC (5 mg/L) and isothiazolinone (0.1 mg/L), effectively controlling cyanobacteria while minimizing harm to Vallisneria natans and reducing nutrient loads and microcystin accumulation. Algaecide application enhanced microbial diversity in water and leaves, shifting the dominant community from cyanobacteria to organisms adapted to the post-cyanobacterial decay environment. Metabolomic analysis indicated increased secretion of lipids and organic acids by cyanobacteria in response to algaecide stress. High concentrations of NaDCC and isothiazolinone disrupted nitrogen metabolism in cyanobacteria and induced ROS overproduction, affecting unsaturated fatty acid synthesis and other metabolic pathways. These findings highlight the importance of exploring different combinations of algaecides to reduce their concentrations, balance algal control with ecological stability, and offer insights for effective eutrophication management.PMID:39490170 | DOI:10.1016/j.jhazmat.2024.136229

Ecotoxicol Environ Saf. 2024 Oct 26;286:117236. doi: 10.1016/j.ecoenv.2024.117236. Online ahead of print.ABSTRACTBisphenol A (BPA) is an environmental contaminant and can be detected in foodstuffs. Hence, investigating BPA metabolism in humans is crucial because certain BPA metabolites may exhibit similar or even greater be toxicity than does the parent compound. In this study, we used an advanced metabolomics-based data processing approach along with ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) to identify BPA metabolites in human liver enzyme incubation samples, and those metabolites were further detected in human excreta and water body samples in Taiwan. The first stage involved converting full-scan MS files from the incubation samples into feature information; this stage revealed 1056 and 2472 features with dose-response relationships in the BPA and isotopically labeled BPA incubation datasets, respectively. The second stage involved using stable isotope tracing to identify isotopic pairs from the two datasets; this stage revealed 190 isotopic pairs. An additional dose-response experiment was conducted to confirm that all these features with isotopic pairs also exhibited a dose-response relationship. To focus on the primary BPA metabolite features, we excluded those with low intensities (below 50,000). This left us with 86 features, which we then used for our analysis. To confirm these features as possible BPA metabolites, we compared the tandem MS (MS/MS) spectra between BPA and isotopically labeled BPA incubation samples. The results revealed 75 isotopic pairs with matching isotopically labeled MS/MS spectra. Among these identified features, one feature's m/z value matched to that of a previously reported BPA metabolite, and the other 74 features were novel. However, only 9 of them had proposed structures. We further investigated whether these features could be detected in humans or Taiwanese water bodies. Furthermore, 10 and 2 novel metabolites were identified in human urine and fecal samples, respectively; 17 novel metabolites were identified in the water samples. These findings indicate some of these novel metabolites are present not only in humans but also in various water bodies across Taiwan. These identified metabolites are phase I BPA metabolites, suggesting they may have toxic properties. Further research is warranted to investigate the structures of these newly discovered metabolites and assess their potential human health risks.PMID:39490109 | DOI:10.1016/j.ecoenv.2024.117236

Plant Physiol Biochem. 2024 Oct 24;217:109234. doi: 10.1016/j.plaphy.2024.109234. Online ahead of print.ABSTRACTThe increasing effects of climate change are leading to an increase in the number and intensity of extreme events, making it essential to study how plants respond to various stresses occurring simultaneously. A crucial regulator of plant responses to abiotic stress is abscisic acid (ABA), as its accumulation in response to stress leads to transcriptomic and metabolomic changes that contribute to plant stress tolerance. In the present study, we investigated how ABA, stress conditions (salinity, water deficit and their combination) and seasons (autumn-winter and spring-summer) regulate tomato fruit yield and metabolism using tomato wild type (WT) and the ABA-deficient flacca mutant (flc) under stress conditions in cold and warm seasons. Our results showed that the applied stresses did not have the same effect in the warm season as in the cold season. In WT plants, the levels of other flavonoids, lignans and other polyphenols were higher in summer fruits, whereas the levels of anthocyanins, flavanols, flavonols, phenolic acids and stilbenes were higher in winter fruits. Furthermore, the significant increase in anthocyanins and flavonols was associated with the combination of salinity + water deficit in both seasons. Additionally, under certain conditions, flc mutants showed an enrichment of the superclasses of benzenoids and organosulphur compounds. The synthesis of phenolic compounds in flc fruits was also significantly different compared to WT plants. Thus, the metabolic profile of tomato fruits varies significantly with endogenous ABA levels, season of cultivation and applied stress treatments, highlighting the multifactorial nature of plant responses to combined environmental factors.PMID:39490099 | DOI:10.1016/j.plaphy.2024.109234

Water Res. 2024 Oct 19;268(Pt A):122664. doi: 10.1016/j.watres.2024.122664. Online ahead of print.ABSTRACTThe proliferation of pathogenic bacteria and antibiotic resistance genes (ARGs) in the biofilm of drinking water distribution pipes poses a serious threat to human health. This work adopted 15 polyethylene (PE) pipes to study the co-selective effect of dissolved organic matter (DOM) and chlorine on the bacterial community and their antibiotic resistance in biofilm. The results indicated that ozone and granular activated carbon (O3-GAC) filtration effectively removed lignins and proteins from DOM, and chlorine disinfection eliminated carbohydrate and unsaturated hydrocarbons, which both contributed to the inhibition of bacterial growth and biofilm formation. After O3-GAC and disinfection treatment, Porphyrobacter, unclassified_d_bacteria, and Sphingopyxis dominated in the biofilm bacterial community. Correspondingly, the bacterial metabolism pathways, including the phosphotransferase system, phenylalanine, tyrosine and tryptophan biosynthesis, ABC transporters, and starch and sucrose metabolism, were downregulated significantly (p < 0.05), compared to the sand filtration treatment. Under such a situation, extracellular polymeric substances (EPS) secretion was inhibited in biofilm after O3-GAC and disinfection treatment, postponing the interaction between EPS protein and pipe surface, preventing bacteria, especially pathogens, from adhering to the pipe surface to form biofilm, and restraining the spread of ARGs. This study revealed the effects of various water filtration and disinfection processes on bacterial growth, metabolism, and biofilm formation on a molecular level, and validated that the O3-GAC filtration followed by chlorine disinfection is an effective and promising pathway to control the microbial risk of drinking water.PMID:39490093 | DOI:10.1016/j.watres.2024.122664

Anal Chim Acta. 2024 Nov 22;1330:343302. doi: 10.1016/j.aca.2024.343302. Epub 2024 Oct 4.ABSTRACTBACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Currently, the medical diagnosis of SLE mainly relies on the clinical experience of physicians, and there is no universally accepted objective method for diagnosing SLE. Therefore, there is an urgent need to design an intelligent approach to accurately diagnose SLE to assist physicians in formulating appropriate treatment plans. With the rapid development of intelligent medical diagnostic technology, medical data is becoming increasingly multimodal. Multimodal data fusion can provide richer information than single-modal data, and the fusion of multiple modalities can effectively enhance the richness of data features to improve modeling performance.RESULTS: In this paper, a cross-modal specific transfer fusion technique based on infrared spectra and metabolomics is proposed to effectively integrate infrared spectra and metabolomics by fully exploiting the intrinsic relationships between features across different modalities, thus achieving the diagnosis of SLE. In this research, a Decision Level Fusion module is also proposed to fuse the representations of two specific transfers further, obtaining the final prediction scores. Comprehensive experimental results demonstrate that the proposed method significantly improves the performance of SLE prediction, with accuracy and Area Under Curve (AUC) reaching 94.98 % and 97.13 %, respectively, outperforming existing methods.SIGNIFICANCE: Our framework effectively integrates infrared spectra and metabolomics to achieve a more accurate prediction of SLE. Our research indicates that prediction methods based on different modalities outperform those using single-modality data. The Cross-modal Specific Transfer Fusion module effectively captures the complex relationships within each single modality and models the complex relationships between different modalities.PMID:39489981 | DOI:10.1016/j.aca.2024.343302

J Pharm Biomed Anal. 2024 Oct 22;253:116541. doi: 10.1016/j.jpba.2024.116541. Online ahead of print.ABSTRACTRapamycin (Rapa) is an inhibitor of mTOR complex, and its therapeutic effect on liver function was examined in non-alcoholic fatty liver disease (NAFLD) rats here. And the possible mechanism of Rapa in NAFLD was preliminarily elucidated based on the non-targeted metabolomics analysis. Adult male SD rats were fed with a high-fat and high-cholesterol diet (HFD) to establish NAFLD model. For Rapa group, 0.8 mg/(kg.d) Rapa was given to the HFD rats. Ultra-performance liquid chromatography and Q-Tof-mass spectrometry (UPLC and Q-TOF/MS) analysis were applied for the identification of metabolites in the serum of rats, which were annotated using Kyoto Encyclopedia of Genes and Genomes (KEGG). NAFLD rats presented with disturbed liver function, lipid metabolism and oxidative stress, but Rapa exerted a mitigating influence on the disorders. The metabolite profile data identified 579 metabolites that varied remarkably between the Rapa and HFD groups, with the main classes of amino acids and peptides, benzene, lipids and fatty acids. The differential metabolites were mainly involved in biosynthesis of cofactors, bile secretion, and glycerophospholipid metabolism were mainly enriched. In conclusion, Rapa has a potential protective effect against HFD-induced NAFLD, its hepatoprotective effect may achieved through mediating bile secretion and glycerophospholipid metabolism.PMID:39489928 | DOI:10.1016/j.jpba.2024.116541

Metabolomics. 2024 Nov 3;20(6):124. doi: 10.1007/s11306-024-02182-3.ABSTRACTBACKGROUND: The global incidence of hypertension, a condition of elevated blood pressure, is rising alarmingly. According to the World Health Organization's Qatar Hypertension Profile for 2023, around 33% of adults are affected by hypertension. This is a significant public health concern that can lead to serious health complications if left untreated. Metabolic dysfunction is a primary cause of hypertension. By studying key biomarkers, we can discover new treatments to improve the lives of those with high blood pressure.AIMS: This study aims to use explainable artificial intelligence (XAI) to interpret novel metabolite biosignatures linked to hypertension in Qatari Population.METHODS: The study utilized liquid chromatography-mass spectrometry (LC/MS) method to profile metabolites from biosamples of Qatari nationals diagnosed with stage 1 hypertension (n = 224) and controls (n = 554). Metabolon platform was used for the annotation of raw metabolite data generated during the process. A comprehensive series of analytical procedures, including data trimming, imputation, undersampling, feature selection, and biomarker discovery through explainable AI (XAI) models, were meticulously executed to ensure the accuracy and reliability of the results.RESULTS: Elevated Vanillylmandelic acid (VMA) levels are markedly associated with stage 1 hypertension compared to controls. Glycerophosphorylcholine (GPC), N-Stearoylsphingosine (d18:1/18:0)*, and glycine are critical metabolites for accurate hypertension prediction. The light gradient boosting model yielded superior results, underscoring the potential of our research in enhancing hypertension diagnosis and treatment. The model's classification metrics: accuracy (78.13%), precision (78.13%), recall (78.13%), F1-score (78.13%), and AUROC (83.88%) affirm its efficacy. SHapley Additive exPlanations (SHAP) further elucidate the metabolite markers, providing a deeper understanding of the disease's pathology.CONCLUSION: This study identified novel metabolite biomarkers for precise hypertension diagnosis using XAI, enhancing early detection and intervention in the Qatari population.PMID:39489869 | DOI:10.1007/s11306-024-02182-3

Sci Rep. 2024 Nov 3;14(1):26494. doi: 10.1038/s41598-024-78359-6.ABSTRACTMyocarditis is a common disease of the cardiovascular and immune systems, but the relationship between relevant blood metabolites and the risk of myocarditis has not been well-established. To identify potential biometabolic markers associated with myocarditis, we conducted a two-sample Mendelian randomization (MR) study. We performed preliminary MR analysis using the inverse variance weighted (IVW) method, supplemented by MR-Egger, weighted median, and weighted mode methods to adjust for false discovery rate (FDR). Confounders were screened using the GWAS Catalog website. Sensitivity analyses included Cochrane Q-test, Egger regression, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), scatterplots, funnel plots, and forest plots. For genetic and directional analysis, we employed co-localization analysis and the Steiger test. MR analysis was performed using the FinnGen database and meta-analysis was performed using the IEU database. MR analysis identified significant correlations for five metabolic biomarkers after FDR correction. These included four known metabolites: kynurenine, 1-stearoyl-GPE (18:0), deoxycarnitine, and 5-acetylamino-6-formylamino-3-methyluracil, as well as one unknown metabolite, X-25,422. Among these, kynurenine (OR = 1.441, 95%CI = 1.089-1.906, p-value = 0.018) and 1-stearoyl-GPE (18:0) (OR = 1.263, 95%CI = 1.029-1.550, p-value = 0.029) were identified as risk factors for myocarditis, while deoxycarnitine (OR = 0.813, 95%CI = 0.676-0.979, p-value = 0.029), 5-acetylamino-6-formylamino-3-methyluracil (OR = 0.864, 95% CI = 0.775-0.962, p-value = 0.018), and X-25,422 (OR = 0.721, 95%CI = 0.587-0.886, p-value = 0.009) were found to be protective factors. No evidence of heterogeneity, horizontal pleiotropy, or sensitivity issues was observed, and no shared genetic factors between exposure and outcome were detected. The causality was in the correct direction. Meta-analysis further confirmed the causal relationship between the five metabolites and myocarditis. This study identifies a causal relationship between five circulating metabolites and myocarditis. Kynurenine, 1-stearoyl-GPE (18:0), deoxycarnitine, X-25,422, and 5-acetylamino-6-formylamino-3-methyluracil may serve as potential drug targets for myocarditis, providing a theoretical basis for the prevention, diagnosis, and treatment of the condition.PMID:39489852 | DOI:10.1038/s41598-024-78359-6

Clin Chim Acta. 2024 Nov 1:120020. doi: 10.1016/j.cca.2024.120020. Online ahead of print.ABSTRACTOne of the essential factors in the appropriate treatment of infections is accurate and timely laboratory diagnosis. The correct diagnosis of infections plays a vital role in determining desirable therapy and controlling the spread of pathogens. Traditional methods of infection diagnosis are limited by several factors such as insufficient sensitivity and specificity, being time-consuming and laborious, having a low ability to distinguish infection from non-infectious inflammatory conditions and a low potential to predict treatment outcomes. Therefore, it is necessary to find innovative strategies for detecting specific biomarkers in order to diagnose infections. The rapid advancement of metabolomics makes it possible to determine the pattern of metabolite changes in the both of pathogen and the host during an infection. Metabolomics is a method used to assess the levels and type of metabolites in an organism. Metabolites are of low-molecular-weight compounds produced as a result of metabolic processes and pathways within cells. Metabolomics provides valuable data to detect accurate biomarkers of specific biochemical features directly related to certain phenotypes or conditions. This study aimed to review the applications and progress of metabolomics as a biomarker for the diagnosis of bacterial infections.PMID:39489271 | DOI:10.1016/j.cca.2024.120020

Int J Biol Macromol. 2024 Nov 1:137112. doi: 10.1016/j.ijbiomac.2024.137112. Online ahead of print.ABSTRACTHyperuricemia (HUA) is a common metabolic disorder that often accompanies kidney diseases such as tubule damage and renal interstitial fibrosis. The preventive and therapeutic effects of Dioscorea septemloba, an anti-HUA herb, polysaccharide of which was considered as the main active ingredient on HUA, need to be explored. The major polysaccharide component, BXP, was purified from Dioscorea septemloba, with an average molecular weight of 10.432 kDa. Structural analysis inferred that BXP backbone was composed of t-β-D-Glcp-(1 → 4)-α-D-Glcp-(1 → 4)-α-D-Glcp-(1 → 4, 3)-β-D-Glcp-(1→, along with the side chain of →1)-α-D-Glcp-(6, 4 → 3, 4)-β-D-Glcp-(1→. The HUA mouse model was further established to clarify the underlying effect of BXP on HUA alleviation. As results shown, BXP decreased serum uric acid by inhibiting XOD and regulating urate transporter expression (GLUT9, OAT3, OAT1, URAT1 and ABCG2) in HUA mice, as well as relieving kidney and liver damage. Moreover, results of microbiome and metabolomics indicated that BXP improved the abundance of gut bacteria and reversed the Lipids-related metabolism disorder caused by HUA. This study indicated that BXP had potential to alleviate HUA and kidney disease through the gut-kidney axis in mice.PMID:39489240 | DOI:10.1016/j.ijbiomac.2024.137112

Gene. 2024 Nov 1:149050. doi: 10.1016/j.gene.2024.149050. Online ahead of print.ABSTRACTAminopeptidase N (ANPEP), a membrane-associated ectoenzyme, has been identified as a susceptibility gene for type 2 diabetes (T2D) by genome-wide association and transcriptome studies; however, the mechanisms by which this gene contributes to disease pathogenesis remain unclear. The aim of this study was to determine the comprehensive contribution of ANPEP polymorphisms to T2D risk and annotate the underlying mechanisms. A total of 3206 unrelated individuals including 1579 T2D patients and 1627 controls were recruited for the study. Twenty-three common functional single nucleotide polymorphisms (SNP) of ANPEP were genotyped by the MassArray-4 system. Six polymorphisms, rs11073891, rs12898828, rs12148357, rs9920421, rs7111, and rs25653, were found to be associated with type 2 diabetes (Pperm ≤ 0.05). Common haplotype rs9920421G-rs4932143G-rs7111T was strongly associated with increased risk of T2D (Pperm = 5.9 × 10-12), whereas two rare haplotypes such as rs9920421G-rs4932143C-rs7111T (Pperm = 6.5 × 10-40) and rs12442778A-rs12898828A-rs6496608T-rs11073891C (Pperm = 1.0 × 10-7) possessed strong protection against disease. We identified 38 and 109 diplotypes associated with T2D risk in males and females, respectively (FDR ≤ 0.05). ANPEP polymorphisms showed associations with plasma levels of fasting blood glucose, aspartate aminotransferase, total protein and glutathione (P < 0.05), and several haplotypes were strongly associated with the levels of reactive oxygen species and uric acid (P < 0.0001). A deep literature analysis has facilitated the formulation of a hypothesis proposing that increased plasma levels of ANPEP as well as liver enzymes such as aspartate aminotransferase, alanine aminotransferase and gammaglutamyltransferase serve as an adaptive response directed towards the restoration of glutathione deficiency in diabetics by stimulating the production of amino acid precursors for glutathione biosynthesis.PMID:39489227 | DOI:10.1016/j.gene.2024.149050

Free Radic Biol Med. 2024 Nov 1:S0891-5849(24)01020-7. doi: 10.1016/j.freeradbiomed.2024.10.312. Online ahead of print.ABSTRACTDecreased nicotinamide adenine dinucleotide (NAD+) content has been shown to contribute to metabolic dysfunction during aging, including polycystic ovary syndrome (PCOS). However, the effect of NAD+ on ovulatory dysfunction in PCOS by regulating glycolysis has not been reported. Based on the observations of granulosa cells (GCs) transcriptome data from the Gene Expression Omnibus (GEO) database, the signal pathways including glycolysis and nicotinate-nicotinamide metabolism were significantly enriched, and most genes of the above pathway like LDHA and SIRT2 were down-regulated in PCOS patients. Therefore, the PCOS rat model was established by combining letrozole with a high-fat diet (HFD), we demonstrate that in vivo supplementation of nicotinamide mononucleotide (NMN) significantly improves the ovulatory dysfunction by facilitating the follicular development, promoting luteal formation, as well the fertility in PCOS rats. Furthermore, target energy metabolomics and transcriptome results showed that NMN supplementation ameliorates the lactate production by activating glycolytic process in the ovary. In vitro, when NAD+ synthesis and SIRT2 expression were inhibited, lactate content in KGN cells was decreased and LDHA expression was significantly inhibited. We confirmed that FK866 can enhance the acetylation of LDHA on 293T cells by Co-immunoprecipitation (Co-IP) assay. We also observed that inhibition of NAD+ synthesis can reduce the activity and increase the apoptosis of KGN cells. Overall, these benefits of NMN were elucidated and the Nampt/SIRT2/LDHA pathway mediated lactate production in granulosa cells played an important role in the improvement of follicular development disorders in PCOS. This study will provide experimental evidence for the clinical application of NMN in the treatment of PCOS in the future.PMID:39489197 | DOI:10.1016/j.freeradbiomed.2024.10.312

Poult Sci. 2024 Oct 19;103(12):104433. doi: 10.1016/j.psj.2024.104433. Online ahead of print.ABSTRACTAccompanied by the accelerated growth rate of chickens, the quality of chicken meat has deteriorated in recent years. Wooden breast (WB) is a severe myopathy affecting meat quality, and its pathophysiology depends on gene expression and intercellular interactions of various cell types, which are not yet fully understood. We have performed a comprehensive transcriptomic and metabolomic atlas of chicken WB muscle. Our data showed a significant increase in the number of immune cells, WB muscle displayed a unique cluster of macrophages (cluster 11), distinct from the M1 and M2 macrophages. Regarding the myocytes, the most significant differences were the decrease in cell number and the intensification of fatty deposits. Satellite cells were involved in muscle repair and regeneration producing more collagen. Interestingly, the interaction network in the WB group was weaker compared to that in normal breast muscle. Additionally, we found six key differential metabolites across 22 pathways. When WB occurs, myocytes and endothelial cells undergo apoptosis, macrophages are activated and exert immune functions, satellite cells participate in muscle rebuilding and repair, and the content of metabolites undergoes significant changes. This cell transcriptome profile provides an essential reference for future studies on the development and remodeling of WB.PMID:39489032 | DOI:10.1016/j.psj.2024.104433

J Hazard Mater. 2024 Oct 28;480:136342. doi: 10.1016/j.jhazmat.2024.136342. Online ahead of print.ABSTRACTThe ecological safety of copper oxide nanoparticles (CuO NPs) in the environment determines the advancement of nano-agriculture owing to breakthroughs in nanotechnology; however, the release of Cu2+ is an uncontrollable factor. Currently, the trade-off mechanisms of CuO NPs and Cu2+ dominating the potential hazards of plant-nano systems remain unclear. This study proposed the trade-off strategy for reconstructing physiological responses and metabolic profiles and deciphered the differential regulation of dominant CuO NPs and Cu2+ in plants. The results showed that 100 and 500 mg/kg CuO NPs promoted root fresh weight but reduced shoot fresh weight, while 1000 mg/kg Cu2+ demonstrated the strongest inhibition on both roots and shoots. The net photosynthetic perturbation in photosynthetic disorders is accompanied by superoxide anion and hydrogen peroxide accumulation, which are severe under 1000 mg/kg CuO NPs and Cu2+ stress. Metabolomics revealed that CuO NPs significantly altered coumaric acid and derivatives, for example, down-regulating coumaroyl hexoside (isomers of 690 and 691) by 40.79 %. Additionally, Cu2+ treatment severely interfered with the dominant metabolic response, activating plant hormone signal transduction and α-linolenic acid metabolism. The trade-off strategies of galactose metabolism, amino sugar and nucleotide sugar metabolism, pantothenate and coenzyme A (CoA) biosynthesis, and β-alanine metabolism as differential metabolism were confirmed by comparing the CuO NPs and Cu2+ exposure. Protein secondary structure analysis revealed specific regulation of protein conformation upon exposure to CuO NPs and Cu2+. These findings provide new insights into differential metabolism and environmental effects in plant-nano systems.PMID:39488971 | DOI:10.1016/j.jhazmat.2024.136342

J Environ Manage. 2024 Nov 2;371:123122. doi: 10.1016/j.jenvman.2024.123122. Online ahead of print.ABSTRACTThe escalation of major ion concentrations in freshwater and soil poses diverse effects on ecosystems and the environment. Excessive ions can exhibit toxicity to aquatic organisms and terrestrial plants. Currently, research on ion toxicity primarily focuses on cation toxicity. Notably, there is a noticeable research gap in understanding the impact of chloride ion (Cl-) on plant growth and development, as well as on the defense mechanisms against Cl- toxicity. In the present study, sampling was conducted on major rivers in China to measure Cl- concentrations. The results revealed that certain rivers exhibited excessive levels of Cl-, emphasizing the critical need to address Cl- toxicity issues. Subsequently, when salt-tolerant cotton seedlings were subjected to various chloride treatments, it was observed that excessive Cl- severely hindered plant growth and development. A combined analysis of transcriptomic and metabolomic data shed light on significantly enriched pathways related to galactose metabolism, arginine and proline metabolism, carotenoid metabolism, and alpha-linolenic acid metabolism under chloride stress. In summary, this research provides a scientific foundation and references for environmental management and water resource protection and offers novel insights for mitigating the adverse impacts of Cl-, thereby contributing to the preservation of ecosystem health.PMID:39488955 | DOI:10.1016/j.jenvman.2024.123122