PubMed

Front Pharmacol. 2023 Oct 20;14:1278838. doi: 10.3389/fphar.2023.1278838. eCollection 2023.ABSTRACTRetinyl palmitate (RP) is a vitamin A derivative that has been widely used in anti-aging and skin treatment. The aim of this study is to investigate the effect of RP on UVB (Ultraviolet radiation B) induced photoaging and its potential mechanism. Immunofluorescence assay demonstrates that RP can reduce collagen degradation in skin cells by UVB radiation and reduce apoptosis of skin cells. Cell migration assay reveals that RP can increase cell migration rate, helping to repair skin damage and restore cell viability. Immunohistochemical assays indicate that RP can significantly reduce the expression of IL-6, IL-1β, TNF-α induced by UVB radiation. Moreover, metabolomics and transcriptomics results suggest that RP regulates several metabolic pathways and gene expression, particularly in inflammatory signaling pathways, collagen synthesis and apoptosis, exhibiting significant regulatory effects. Furthermore, network pharmacological analysis predicts that RP may affect UVB-induced photoaging by regulating multiple key proteins and signaling pathways. Overall, this study demonstrates that RP has significant anti-photoaging ability, acting through several pathways including inhibition of inflammatory response, promotion of collagen synthesis and inhibition of apoptosis. These results provide a scientific basis for the application of RP in skin anti-photoaging and therapy, enabling the potential usage of RP to skin care products.PMID:37927602 | PMC:PMC10622759 | DOI:10.3389/fphar.2023.1278838

iScience. 2023 Jul 10;26(11):107332. doi: 10.1016/j.isci.2023.107332. eCollection 2023 Nov 17.ABSTRACTChronic kidney disease (CKD) is a common disease that seriously endangers human health. However, the potential relationship between xanthine oxidoreductase (XOR) activity and CKD remains unclear. In this study, we used clinical data, CKD datasets from the Gene Expression Omnibus database, and untargeted metabolomics to explain the relationship between XOR activity and CKD. First, XOR activity showed high correlation with the biomarkers of CKD, such as serum creatinine, blood urea nitrogen, uric acid, and estimated glomerular filtration rate. Then, we used least absolute shrinkage and selection operator logical regression algorithm and random forest algorithm to screen CKD molecular markers from differentially expressed genes, and the results of qRT-PCR of XDH, KOX-1, and ROMO1 were in accordance with the results of bioinformatics analyses. In addition, untargeted metabolomics analysis revealed that the purine metabolism pathway was significantly enriched in CKD patients in the simulated models of kidney fibrosis.PMID:37927553 | PMC:PMC10622700 | DOI:10.1016/j.isci.2023.107332

JIMD Rep. 2023 Sep 7;64(6):403-409. doi: 10.1002/jmd2.12388. eCollection 2023 Nov.ABSTRACTN-acetyl glutamate synthase (NAGS) deficiency (OMIM #: 237310) is a rare urea cycle disorder that usually presents early in life with hyperammonemia. NAGS catalyzes the synthesis of N-acetyl glutamate (NAG) which functions as an activator of the carbamoyl phosphate synthetase-1 mediated conversion of ammonia to carbamoyl phosphate. The absence of NAG results in a proximal urea cycle disorder which can result in severe neurologic sequelae secondary to hyperammonemia and even death. Unlike the other urea cycle disorders, a specific pharmacological treatment for NAGS deficiency exists in the form of carglumic acid, an analog of NAG. Here we present a 29-year-old previously healthy female who presented with hyperammonemia and obtundation just after the birth of her first child. Exome sequencing revealed two novel variants in the NAGS gene, and plasma metabolomics revealed extremely low levels of NAG. Carglumic acid treatment led to prompt resolution of her biochemical abnormalities and symptoms. She tolerated two subsequent pregnancies, 2 years and 6 years after her initial presentation, while taking carglumic acid, and breastfed her third child, all without complications in the mother or children. This case report emphasizes the importance of considering urea cycle disorders in previously-healthy adults presenting with neurological symptoms during periods of metabolic stress, including the postpartum period. It also highlights the efficacious and safe use of carglumic acid during pregnancy and while breastfeeding.PMID:37927481 | PMC:PMC10623101 | DOI:10.1002/jmd2.12388

Front Oncol. 2023 Oct 19;13:1305140. doi: 10.3389/fonc.2023.1305140. eCollection 2023.NO ABSTRACTPMID:37927477 | PMC:PMC10625419 | DOI:10.3389/fonc.2023.1305140

J Alzheimers Dis. 2023 Nov 2. doi: 10.3233/JAD-230122. Online ahead of print.ABSTRACTBACKGROUND: Long-term exposure to air pollution has been associated with changes in levels of metabolites measured in the peripheral blood. However, most research has been conducted in ethnically homogenous, young or middle-aged populations.OBJECTIVE: To study the relationship between the plasma metabolome and long-term exposure to three air pollutants: particulate matter (PM) less than 2.5μm in aerodynamic diameter (PM2.5), PM less than 10μm in aerodynamic diameter (PM10), and nitrogen dioxide (NO2) in an ethnically diverse, older population.METHODS: Plasma metabolomic profiles of 107 participants of the Washington Heights and Inwood Community Aging Project in New York City, collected from 1995-2015, including non-Hispanic white, Caribbean Hispanic, and non-Hispanic Black older adults were used. We estimated the association between each metabolic feature and predicted annual mean exposure to the air pollutants using three approaches: 1) A metabolome wide association study framework; 2) Feature selection using elastic net regression; and 3) A multivariate approach using partial-least squares discriminant analysis.RESULTS: 79 features associated with exposure to PM2.5 but none associated with PM10 or NO2. PM2.5 exposure was associated with altered amino acid metabolism, energy production, and oxidative stress response, pathways also associated with Alzheimer's disease. Three metabolites were associated with PM2.5 exposure through all three approaches: cysteinylglycine disulfide, a diglyceride, and a dicarboxylic acid. The relationship between several features and PM2.5 exposure was modified by diet and metabolic diseases.CONCLUSIONS: These relationships uncover the mechanisms through which PM2.5 exposure can lead to altered metabolic outcomes in an older population.PMID:37927256 | DOI:10.3233/JAD-230122

Plant Cell Physiol. 2023 Oct 31:pcad137. doi: 10.1093/pcp/pcad137. Online ahead of print.ABSTRACTWounding caused by insects or abiotic factors such as wind and hail can cause severe stress for plants. Intrigued by the observation that wounding induces expression of genes involved in surface wax synthesis in a jasmonoyl-isoleucine (JA-Ile)-independent manner, the role of wax biosynthesis and respective genes upon wounding was investigated. Wax, a lipid-based barrier, protects plants both from environmental threats as well as from an uncontrolled loss of water. Its biosynthesis is described to be regulated by abscisic acid (ABA), whereas the main wound-signal is the hormone JA-Ile. We show in this study, that genes coding for enzymes of surface wax synthesis are induced upon wounding in Arabidopsis thaliana leaves in a JA-Ile-independent but ABA-dependent manner. Furthermore, the ABA-dependent transcription factor MYB96 is a key regulator of wax biosynthesis upon wounding. On the metabolite level, wound-induced wax accumulation is strongly reduced in JA-Ile-deficient plants, but this induction is only slightly decreased in ABA-reduced plants. To further analyze the ABA-dependent wound response, we conducted wounding experiments in high humidity. They show that high humidity prevents the wound-induced wax accumulation in A. thaliana leaves. Together the data presented in this study show that wound-induced wax accumulation is JA-Ile-dependent on the metabolite level, but the expression of genes coding for enzymes of wax synthesis is regulated by ABA.PMID:37927069 | DOI:10.1093/pcp/pcad137

J Epidemiol. 2023 Nov 4. doi: 10.2188/jea.JE20230170. Online ahead of print.ABSTRACTBACKGROUND: Heated tobacco products (HTPs) have gained global popularity, but their health risks remain unclear. Therefore, the current study aimed to identify plasma metabolites associated with smoking and HTP use in a large Japanese population to improve health risk assessment.METHODS: Metabolomics data from 9,922 baseline participants of the Tsuruoka Metabolomics Cohort Study (TMCS) were analyzed to determine the association between smoking habits and plasma metabolites. Moreover, alterations in smoking-related metabolites among HTP users were examined based on data obtained from 3,334 participants involved from April 2018 to June 2019 in a follow-up survey.RESULTS: Our study revealed that cigarette smokers had metabolomics profiles distinct from never smokers, with 22 polar metabolites identified as candidate biomarkers for smoking. These biomarker profiles of HTP users were closer to those of cigarette smokers than those of never smokers. The concentration of glutamate was higher in cigarette smokers, and biomarkers involved in glutamate metabolism were also associated with cigarette smoking and HTP use. Network pathway analysis showed that smoking was associated with the glutamate pathway, which could lead to endothelial dysfunction and atherosclerosis of the vessels.CONCLUSIONS: Our study showed that the glutamate pathway is affected by habitual smoking. These changes in the glutamate pathway may partly explain the mechanism by which cigarette smoking causes cardiovascular disease. HTP use was also associated with glutamate metabolism, indicating that HTP use may contribute to the development of cardiovascular disease through mechanisms similar to those in cigarette use.PMID:37926518 | DOI:10.2188/jea.JE20230170

Phytother Res. 2023 Nov 5. doi: 10.1002/ptr.7995. Online ahead of print.ABSTRACTThere is a large demand for nutraceuticals in the market and studies related to their action are needed. In this paper, the antimicrobial activity and the immunomodulatory effect of a nutraceutical formulation containing 14.39% of ascorbic acid, 7.17% of coenzyme Q10, 1.33% of Echinacea polyphenols, 0.99% of pine flavan-3-ols, 0.69% of resveratrol and 0.023% of Echinacea alkylamides were studied using in vitro assays and cell-based metabolomics. Chromatographic analysis allowed us to study the nutraceutical composition. The antibacterial activity was evaluated on S. aureus, K. pneumoniae, P. aeruginosa, E. coli, H. influenzae, S. pyogenes, S. pneumoniae and M. catarrhalis. The immunomodulatory activity was assessed on human macrophages and dendritic cells. The production of IL-1β, IL-12p70, IL-10 and IL-8 was evaluated on culture medium by ELISA and the activation/maturation of dendritic cells with cytofluorimetric analysis. Treated and untreated macrophages and dendritic cell lysates were analysed by liquid chromatography coupled with high-resolution mass spectrometry, and results were compared using multivariate data analysis to identify biological markers related to the treatment with the food supplement. The food supplement decreased K. pneumoniae, P. aeruginosa, E. coli, Methicillin-resistant Staphylococcus aureus (MRSA) and M. catharralis growth, reduced the inflammatory response in macrophages exposed to lipopolysaccharide (LPS) and modulated the activation and maturation of the dendritic cells. Oxidized phospholipids were identified as the main biological markers of treated cell lysates, compared with controls.PMID:37926430 | DOI:10.1002/ptr.7995

Environ Pollut. 2023 Nov 3:122872. doi: 10.1016/j.envpol.2023.122872. Online ahead of print.ABSTRACTTire wear particles (TWPs) generated by vehicle tires are ubiquitous in soil ecosystems, while their impact on soil biota remains poorly understood. In this study, we investigated the effects of TWPs (0.1%, 0.7%, and 1.5% of dry soil weight) on the growth and metabolism of mung bean (Vigna radiata) plants over 32 days in soil pots. We found that TWPs-treated soils had high levels of heavy metals and polycyclic aromatic hydrocarbons (PAHs). However, there was no significant impact of TWPs exposure on plant growth, suggesting that mung bean plants have a degree of tolerance to TWPs. Despite the lack of impact on plant growth, exposure to TWPs had significant effects on soil enzyme activities, with a decrease of over 50% in urease and dehydrogenase activity. Furthermore, TWPs exposure resulted in marked changes in the plant metabolite profile, including altered levels of sugars, carboxylic acids, and amino acids, indicating altered nitrogen and amino acid-related metabolic pathways. TWPs exposure also disrupted the rhizospheric and bulk soil microbiota, with a decrease in the abundance of bacterial (Blastococcus) and fungal (Chaetomium) genera involved in nitrogen cycles and suppressing plant diseases. In summary, our study provides new insights into the effects of TWPs on plants and soil, highlighting the potential ecological consequences of TWPs pollution in terrestrial ecosystems and underscoring the need for further research in this area.PMID:37926408 | DOI:10.1016/j.envpol.2023.122872

Int J Biol Macromol. 2023 Nov 3:127808. doi: 10.1016/j.ijbiomac.2023.127808. Online ahead of print.ABSTRACTGut microbiota and their metabolic processes depend on the intricate interplay of gut microbiota and their metabolic processes. Bacillus licheniformis, a beneficial food supplement, has shown promising effects on stabilizing gut microbiota and metabolites. However, the precise mechanisms underlying these effects remain elusive. In this study, we investigated the impact of polysaccharide-producing B. licheniformis as a dietary supplement on the gut microbiome and metabolites through a combination of scanning electron microscopy (SEM), histological analysis, high-throughput sequencing (HTS), and metabolomics. Our findings revealed that the B. licheniformis-treated group exhibited significantly increased jejunal goblet cells. Moreover, gut microbial diversity was lower in the treatment group as compared to the control, accompanied by noteworthy shifts in the abundance of specific bacterial taxa. Enrichment of Firmicutes, Lachnospiraceae, and Clostridiales_bacterium contrasted with reduced levels of Campylobacterota, Proteobacteria, Parasutterella, and Helicobacter. Notably, the treatment group showed significant weight gain after 33 days, emphasizing the polysaccharide's impact on host metabolism. Delving into gut metabolomics, we discovered significant alterations in metabolites. Nine metabolites, including olprinone, pyruvic acid, and 2-methyl-3-oxopropanoate, were upregulated, while eleven, including defoslimod and voclosporin, were down-regulated, shedding light on phenylpropanoid biosynthesis, tricarboxylic acid cycle (TCA cycle), and the glucagon signaling pathway. This comprehensive multi-omics analysis offers compelling insights into the potential of B. licheniformis as a dietary polysaccharide supplement for gut health and host metabolism, promising significant implications for gut-related issues.PMID:37926310 | DOI:10.1016/j.ijbiomac.2023.127808

Life Sci. 2023 Nov 3:122237. doi: 10.1016/j.lfs.2023.122237. Online ahead of print.ABSTRACTAIMS: Ewing's Sarcoma is an extremely aggressive tumor in children. The disease is associated with highly metastatic rate, especially at the time of diagnosis, contributing to a lower survival rate and poor prognosis. The study aimed to identify predictive biomarkers for metastatic Ewing's sarcoma through in-depth analysis of the plasma proteome profile of pediatric Ewing's sarcoma patients.MAIN METHODS: Plasma samples from Ewing's sarcoma patients and control individuals were profiled using both shotgun and dimethyl-labeled proteomics analysis. Subsequently, Ewing's sarcoma patients were further stratified according to their metastatic state and chemotherapy response. Western blot was used for validation. Univariate and multivariate analyses were performed to determine proteome metastasis predictors. Receiver operating characteristic (ROC) analysis was done to assess the diagnostic significance of the potential plasma Ewing's sarcoma biomarkers.KEY FINDINGS: Our results revealed a set of proteins significantly associated with the metastatic Ewing's sarcoma disease profile. These proteins include ceruloplasmin and several immunoglobulins. Additionally, our study disclosed significant differentially expressed proteins in pediatric Ewing's sarcoma, including CD5 antigen-like, clusterin, and dermcidin. Stable isotope dimethyl labeling and western blot further confirmed our results, strengthening the impact of such proteins in disease development. Furthermore, an unbiased ROC curve evaluated and confirmed the predictive power of these biomarker candidates.SIGNIFICANCE: This study presented potential empirical predictive circulating biomarkers for determining the disease status of pediatric Ewing's sarcoma, which is vital for early prediction.PMID:37926299 | DOI:10.1016/j.lfs.2023.122237

J Hazard Mater. 2023 Oct 29;463:132839. doi: 10.1016/j.jhazmat.2023.132839. Online ahead of print.ABSTRACTShale gas hydraulic fracturing generates flowback waters that pose a threat to aquatic organisms if released into the environment. In order to prevent adverse effects on aquatic ecosystems, multiple lines of evidence are needed to guide better decisions and management actions. This study employed a multi-disciplinary approach, combining direct toxicity assessment (DTA) on the water flea Daphnia carinata and LC-MS metabolomics analysis to determine the impact of a major ion salinity control (SC) and a cumulative flowback shale gas wastewater (SGW) from a well in the Beetaloo Sub-basin, Northern Territory, Australia. The exposures included a culture water control, simply further referred to as 'control', SC at 1% and 2% (v/v) and SGW at 0.125, 0.25, 0.5, 1% and 2% (v/v). The results showed that reproduction was significantly increased at SGW 0.5%, and significantly decreased when exposed to SC 2%. SGW 2% was found to be acutely toxic for the D. carinata (< 48-h). Second generation (F1) of D. carinata exposed to 0.125-1% SGW generally saw reduced activity in four oxidative biomarkers: glutathione S-transferase, lipid peroxidation, reactive oxygen species, and superoxide dismutase. At the metabolomics level, we observed significant changes in 103 metabolites in Daphnia exposed to both SGW and elevated salinity, in comparison to the control group. These changes indicate a range of metabolic disturbances induced by SGW and salinity, such as lipid metabolism, amino acid metabolism, nucleotide synthesis, energy production, and the biosynthesis of crucial molecules like hormones and pigments. These multiple lines of evidence approach not only highlights the complexities of SGW's impact on aquatic ecosystems but also underscores the importance of informed decision-making and management practices to safeguard the environment and its inhabitants.PMID:37926015 | DOI:10.1016/j.jhazmat.2023.132839

Comput Biol Med. 2023 Nov 1;167:107661. doi: 10.1016/j.compbiomed.2023.107661. Online ahead of print.ABSTRACTIn the realm of unraveling COVID-19's intricacies, numerous metabolomic investigations have been conducted to discern the unique metabolic traits exhibited within infected patients. These endeavors have yielded a substantial reservoir of potential data pertaining to metabolic biomarkers linked to the virus. Despite these strides, a comprehensive and meticulously structured database housing these crucial biomarkers remains absent. In this study, we developed MetaboliteCOVID, a manually curated database of COVID-19-related metabolite markers. The database currently comprises 665 manually selected entries of significantly altered metabolites associated with early diagnosis, disease severity, prognosis, and drug response in COVID-19, encompassing 337 metabolites. Additionally, the database offers a user-friendly interface, containing abundant information for querying, browsing, and analyzing COVID-19-related abnormal metabolites in different body fluids. In summary, we believe that this database will effectively facilitate research on the functions and mechanisms of COVID-19-related metabolic biomarkers, thereby advancing both basic and clinical research on COVID-19. MetaboliteCOVID is free available at: https://cellknowledge.com.cn/MetaboliteCOVID.PMID:37925911 | DOI:10.1016/j.compbiomed.2023.107661

J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Oct 31;1230:123906. doi: 10.1016/j.jchromb.2023.123906. Online ahead of print.ABSTRACTAn important area within clinical research is in vivo metabolism of ketone bodies (β-hydroxybutyrate and acetoacetate) and in connection metabolites that may affect their production and/or cellular transport such as the keto-acids from the branched-chain amino acids, lactate and pyruvate. To determine in vivo metabolite turnover, availability of accurate and sensitive methods for analyzing the plasma concentrations of these metabolites and their stable isotopically labeled enrichments is mandatory. Therefore, the present study describes a high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous analysis of ketone bodies, α-keto acids, lactate, pyruvate, and their tracer enrichments in humans using 2 different derivatization techniques with 4-bromo-N-methylbenzylamine and O-benzylhydroxylamine as derivatization reagents, and 1-ethyl-3-dimethylaminopropyl carbodiimide as coupling compound followed by a single LC-MS/MS run. The method was validated for matrix effects, linearity, accuracy, precision, recovery, stability, and enrichment (ratio) analysis of a stable isotopically labelled analytes (tracers) continuously infused in humans divided by the unlabeled endogenous analyte (tracee) that makes it possible to quantify the analyte in vivo synthesis and degradation rates. The applied parallel derivatization procedure yielded good sensitivity for all analytes of interest and their tracers. Despite the double derivatization method, mixing the ethyl acetate portions at the final stage made it possible to simultaneously analyze all compounds in a single LC-MS/MS run. Moreover, the liquid chromatography method was optimized to robustly quantify the keto acids derived from leucine (α-keto-isocaproic acid) and isoleucine (α-keto-β-methylvaleric acid), the compounds with similar chemical structure and identical molecular weights. The presented method is designed and validated for human plasma. However, care should be taken in blood sampling and processing procedures as well as quick freezing and storage at -80 °C due to the instability of especially acetoacetate.PMID:37925904 | DOI:10.1016/j.jchromb.2023.123906

Phytomedicine. 2023 Oct 31;122:155171. doi: 10.1016/j.phymed.2023.155171. Online ahead of print.ABSTRACTBACKGROUND: Addressing brain metastases in cancer presents substantial challenges due to limited therapeutic options and high mortality rates. In clinical practice, the amalgamation of traditional Chinese medicine with other treatment modalities has exhibited noteworthy efficacy in managing disease progression and enhancing quality of life.OBJECTIVE: To substantiate the regulatory effects of Shenqi Fuzheng Injection (SFI) on the microenvironment of melanoma brain metastases and appraise whether SFI augments the anti-tumour effects of immune checkpoint inhibitors, with a specific focus on investigating the mechanisms underlying SFI's actions.METHODS: Initially, we established a B16-F10 brain transplant tumour model in C57BL/6 mice using a stereotaxic apparatus. The efficacy of the drug was evaluated through in vivo imaging technology, HE staining, and immunofluorescence. Mass Cytometry (CyTOF) and flow cytometry were employed to analyse the impact of SFI on immune cell subpopulations in the tumour microenvironment. Subsequently, transcriptome sequencing and metabolomics were utilised to examine the effects of SFI on melanoma-related genes and metabolism. Molecular docking, Western Blot, and ELISA assays were conducted to investigate the targets of SFI in intervening in melanoma fatty acid metabolism. Finally, the anti-tumour effects of SFI in combination with immune checkpoint inhibitors were scrutinised in the brain transplant tumour model.RESULTS: The pharmacological findings demonstrated that SFI inhibits the growth of melanoma brain transplant tumours in a dose-dependent manner. CyTOF, flow cytometry, and immunofluorescence results revealed that SFI significantly diminishes the levels of Myeloid-Derived Suppressor Cells (MDSCs) and Regulatory T cells (Tregs) in the tumour microenvironment while enhancing the levels of CD8+T and CD4+ T cells. Subsequently, transcriptomic and metabolomic findings, both in vitro and in vivo, indicate that SFI significantly inhibits the arachidonic acid metabolism process in melanoma cells. Molecular docking and biological experiments showed that SFI inhibits the expression of D6D and the activity of COX-2, leading to a reduction in downstream PGE2 production. Lastly, SFI significantly enhances the anti-tumour effects of PD-L1 antibody against intracranial melanoma.CONCLUSION: SFI improves the tumour immune microenvironment in melanoma by intervening in fatty acid metabolism, thereby reducing levels of MDSCs and Tregs while increasing levels of CD8+ T and CD4+ T cells. Ultimately, this augmentation leads to enhanced anti-tumour effects of the immune checkpoint inhibitor PD-L1 antibody.PMID:37925891 | DOI:10.1016/j.phymed.2023.155171

Phytomedicine. 2023 Nov 2;122:155179. doi: 10.1016/j.phymed.2023.155179. Online ahead of print.ABSTRACTBACKGROUND: Natural bioactive molecules are important sources for the development of new drugs. However, most of them were limited in clinical applications due to their low aqueous solubility and bioavailability. Oridonin (ORI) is a powerful anticancer compound with above characteristics.OBJECTIVE: This study aimed to find an effective method to improve the bioavailability of poorly soluble natural compounds, and explore the action mechanisms of them to promote their application.RESULTS: In this study, ORI-nicotinamide (NCT) cocrystal was successfully prepared for the first time to overcome the defects of ORI. The solubility and oral bioavailability of cocrystal (COC) increased 1.34 and 1.18 times compared with ORI. Moreover, MTT assay was applied to compare the cytotoxicity of positive control drug sorafenib with ORI and COC. The IC50 values of sorafenib, ORI and COC on HepG2 cells were 7.61, 8.79 and 7.36 nmol·mL-1, which indicated that the cytotoxicity of ORI could be enhanced by cocrystal preparation. The cellular metabolomics was innovatively introduced to gain insight into the difference of cytotoxicity mechanism between ORI and COC. The results showed that there were 78 metabolites with significant differences in content between the two groups, while these differential metabolites were related to 11 metabolic pathways. Among these, glycerophospholipid metabolism and cysteine and methionine metabolism were the significant differential pathways, and the downregulation of PC(14:0/16:1(9z)) and upregulation of homocysteine were the likely main reasons for higher cytotoxicity of COC.CONCLUSIONS: This study has presented novel approaches for enhancing the bioavailability and drug efficacy of natural compounds, while also offering fresh insights into the underlying action mechanisms of pharmaceutical cocrystals.PMID:37925890 | DOI:10.1016/j.phymed.2023.155179

Sci Rep. 2023 Nov 4;13(1):19103. doi: 10.1038/s41598-023-46566-2.ABSTRACTGastrointestinal symptoms are more prevalent in children with autism spectrum disorder (ASD) than in typically developing (TD) children. Constipation is a significant gastrointestinal comorbidity of ASD, but the associations among constipated autism spectrum disorder (C-ASD), microbiota and short-chain fatty acids (SCFAs) are still debated. We enrolled 80 children, divided into the C-ASD group (n = 40) and the TD group (n = 40). In this study, an integrated 16S rRNA gene sequencing and gas chromatography-mass spectrometry-based metabolomics approach was applied to explore the association of the gut microbiota and SCFAs in C-ASD children in China. The community diversity estimated by the Observe, Chao1, and ACE indices was significantly lower in the C-ASD group than in the TD group. We observed that Ruminococcaceae_UCG_002, Erysipelotrichaceae_UCG_003, Phascolarctobacterium, Megamonas, Ruminiclostridium_5, Parabacteroides, Prevotella_2, Fusobacterium, and Prevotella_9 were enriched in the C-ASD group, and Anaerostipes, Lactobacillus, Ruminococcus_gnavus_group, Lachnospiraceae_NK4A136_group, Ralstonia, Eubacterium_eligens_group, and Ruminococcus_1 were enriched in the TD group. The propionate levels, which were higher in the C-ASD group, were negatively correlated with the abundance of Lactobacillus taxa, but were positively correlated with the severity of ASD symptoms. The random forest model, based on the 16 representative discriminant genera, achieved a high accuracy (AUC = 0.924). In conclusion, we found that C-ASD is related to altered gut microbiota and SCFAs, especially decreased abundance of Lactobacillus and excessive propionate in faeces, which provide new clues to understand C-ASD and biomarkers for the diagnosis and potential strategies for treatment of the disorder. This study was registered in the Chinese Clinical Trial Registry ( www.chictr.org.cn ; trial registration number ChiCTR2100052106; date of registration: October 17, 2021).PMID:37925571 | DOI:10.1038/s41598-023-46566-2

Sci Rep. 2023 Nov 4;13(1):19083. doi: 10.1038/s41598-023-46553-7.ABSTRACTUntargeted serum metabolomics was combined with machine learning-powered data analytics to develop a test for the concurrent detection of multiple cancers in women. A total of fifteen cancers were tested where the resulting metabolome data was sequentially analysed using two separate algorithms. The first algorithm successfully identified all the cancer-positive samples with an overall accuracy of > 99%. This result was particularly significant given that the samples tested were predominantly from early-stage cancers. Samples identified as cancer-positive were next analysed using a multi-class algorithm, which then enabled accurate discernment of the tissue of origin for the individual samples. Integration of serum metabolomics with appropriate data analytical tools, therefore, provides a powerful screening platform for early-stage cancers.PMID:37925521 | DOI:10.1038/s41598-023-46553-7

Respir Res. 2023 Nov 4;24(1):265. doi: 10.1186/s12931-023-02576-2.ABSTRACTBACKGROUND: Quantitative interstitial abnormalities (QIA) are an automated computed tomography (CT) finding of early parenchymal lung disease, associated with worse lung function, reduced exercise capacity, increased respiratory symptoms, and death. The metabolomic perturbations associated with QIA are not well known. We sought to identify plasma metabolites associated with QIA in smokers. We also sought to identify shared and differentiating metabolomics features between QIA and emphysema, another smoking-related advanced radiographic abnormality.METHODS: In 928 former and current smokers in the Genetic Epidemiology of COPD cohort, we measured QIA and emphysema using an automated local density histogram method and generated metabolite profiles from plasma samples using liquid chromatography-mass spectrometry (Metabolon). We assessed the associations between metabolite levels and QIA using multivariable linear regression models adjusted for age, sex, body mass index, smoking status, pack-years, and inhaled corticosteroid use, at a Benjamini-Hochberg False Discovery Rate p-value of ≤ 0.05. Using multinomial regression models adjusted for these covariates, we assessed the associations between metabolite levels and the following CT phenotypes: QIA-predominant, emphysema-predominant, combined-predominant, and neither- predominant. Pathway enrichment analyses were performed using MetaboAnalyst.RESULTS: We found 85 metabolites significantly associated with QIA, with overrepresentation of the nicotinate and nicotinamide, histidine, starch and sucrose, pyrimidine, phosphatidylcholine, lysophospholipid, and sphingomyelin pathways. These included metabolites involved in inflammation and immune response, extracellular matrix remodeling, surfactant, and muscle cachexia. There were 75 metabolites significantly different between QIA-predominant and emphysema-predominant phenotypes, with overrepresentation of the phosphatidylethanolamine, nicotinate and nicotinamide, aminoacyl-tRNA, arginine, proline, alanine, aspartate, and glutamate pathways.CONCLUSIONS: Metabolomic correlates may lend insight to the biologic perturbations and pathways that underlie clinically meaningful quantitative CT measurements like QIA in smokers.PMID:37925418 | DOI:10.1186/s12931-023-02576-2

J Equine Vet Sci. 2023 Nov 2:104958. doi: 10.1016/j.jevs.2023.104958. Online ahead of print.ABSTRACTPastures are used for grazing and the production of conserved roughage in horses. Yet, the nutritional profile of the forage varies from spring to late summer, affecting equine nutrient supply and health. In addition, environmental factors may also favor plant contaminants such as mycotoxins. This study aimed to determine the nutritional profile and contaminant load of selected horse pastures from early spring till late summer. The nutrient composition (main macronutrients, macro elements and trace elements), as well as mycotoxins, metabolites, pesticides, and plant-derived compounds of seven horse pastures were analyzed. Each pasture was sampled three times and the samples were categorized according to the status of the pasture plants: ear emergence, early- till full bloom, and drought-damaged vegetation. Drought-damaged pastures demonstrated a rise in the acid to neutral detergent fiber ratio, calcium, iron, and magnesium but lower potassium contents. Mycotoxins and other contaminants were found in the pastures including 64 fungal compounds (ergot alkaloids (13) and metabolites from Fusarium (21), Aspergillus (2), Penicillium (8), Alternaria (8) and other fungal species (12), one bacterial metabolite (cereulide), twelve plant metabolites (including eight phytoestrogens and three cyanogenic glycosides (linamarin, lotaustralin and prunasin)), 11 nonspecific metabolites and six pesticides. Fusarium metabolites showed the highest concentrations among the fungal metabolites (range: 123 - 3873 µg/kg DM) and drought-induced stress increased the contamination levels. In conclusion, there was a dominant effect of the developmental stages of the plants, botanical composition of the pastures and weather conditions on the nutritional composition and presence of contaminants on pastures.PMID:37925115 | DOI:10.1016/j.jevs.2023.104958