PubMed

Front Microbiol. 2023 Oct 20;14:1259015. doi: 10.3389/fmicb.2023.1259015. eCollection 2023.ABSTRACTMethanotrophs play a significant role in methane oxidation, because they are the only biological methane sink present in nature. The methane monooxygenase enzyme oxidizes methane or ammonia into methanol or hydroxylamine, respectively. While much is known about central carbon metabolism in methanotrophs, far less is known about nitrogen metabolism. In this study, we investigated how Methylococcus capsulatus Bath, a methane-oxidizing bacterium, responds to nitrogen source and temperature. Batch culture experiments were conducted using nitrate or ammonium as nitrogen sources at both 37°C and 42°C. While growth rates with nitrate and ammonium were comparable at 42°C, a significant growth advantage was observed with ammonium at 37°C. Utilization of nitrate was higher at 42°C than at 37°C, especially in the first 24 h. Use of ammonium remained constant between 42°C and 37°C; however, nitrite buildup and conversion to ammonia were found to be temperature-dependent processes. We performed RNA-seq to understand the underlying molecular mechanisms, and the results revealed complex transcriptional changes in response to varying conditions. Different gene expression patterns connected to respiration, nitrate and ammonia metabolism, methane oxidation, and amino acid biosynthesis were identified using gene ontology analysis. Notably, key pathways with variable expression profiles included oxidative phosphorylation and methane and methanol oxidation. Additionally, there were transcription levels that varied for genes related to nitrogen metabolism, particularly for ammonia oxidation, nitrate reduction, and transporters. Quantitative PCR was used to validate these transcriptional changes. Analyses of intracellular metabolites revealed changes in fatty acids, amino acids, central carbon intermediates, and nitrogen bases in response to various nitrogen sources and temperatures. Overall, our results offer improved understanding of the intricate interactions between nitrogen availability, temperature, and gene expression in M. capsulatus Bath. This study enhances our understanding of microbial adaptation strategies, offering potential applications in biotechnological and environmental contexts.PMID:37928661 | PMC:PMC10623323 | DOI:10.3389/fmicb.2023.1259015

J Oral Microbiol. 2023 Nov 2;15(1):2277271. doi: 10.1080/20002297.2023.2277271. eCollection 2023.ABSTRACTBACKGROUND: Despite poor oral hygiene, the Baiku Yao (BKY) ethnic group in China presents a low prevalence of dental caries, which may be related to genetic susceptibility. Due to strict intra-ethnic marriage rule, this ethnic has an advantage in studying the interaction between genetic factors and other regulatory factors related to dental caries.METHODS: Peripheral blood from a caries-free adult male was used for whole genome sequencing, and the BKY assembled genome was compared to the Han Chinese genome. Oral saliva samples were collected from 51 subjects for metabolomic and metagenomic analysis. Multiomics data were integrated for combined analysis using bioinformatics approaches.RESULTS: Comparative genomic analysis revealed the presence of structural variations in several genes associated with dental caries. Metabolomic and metagenomic sequencing demonstrated the caries-free group had significantly higher concentration of antimicrobials and higher abundance of core oral health-related microbiota. The functional analysis indicated that cationic antimicrobial peptide resistance and the lipopolysaccharide biosynthesis pathway were enriched in the caries-free group.CONCLUSIONS: Our study provided new insights into the specific regulatory mechanisms that contribute to the low prevalence of dental caries in the specific population and may provide new evidence for the genetic diagnosis and control of dental caries.PMID:37928602 | PMC:PMC10623897 | DOI:10.1080/20002297.2023.2277271

Front Immunol. 2023 Oct 19;14:1267816. doi: 10.3389/fimmu.2023.1267816. eCollection 2023.ABSTRACTINTRODUCTION: Naïve T cells remain in an actively maintained state of quiescence until activation by antigenic signals, upon which they start to proliferate and generate effector cells to initiate a functional immune response. Metabolic reprogramming is essential to meet the biosynthetic demands of the differentiation process, and failure to do so can promote the development of hypofunctional exhausted T cells.METHODS: Here we used 13C metabolomics and transcriptomics to study the metabolism of CD8+ T cells in their complete course of differentiation from naïve over stem-like memory to effector cells and in exhaustion-inducing conditions.RESULTS: The quiescence of naïve T cells was evident in a profound suppression of glucose oxidation and a decreased expression of ENO1, downstream of which no glycolytic flux was detectable. Moreover, TCA cycle activity was low in naïve T cells and associated with a downregulation of SDH subunits. Upon stimulation and exit from quiescence, the initiation of cell growth and proliferation was accompanied by differential expression of metabolic enzymes and metabolic reprogramming towards aerobic glycolysis with high rates of nutrient uptake, respiration and lactate production. High flux in anabolic pathways imposed a strain on NADH homeostasis, which coincided with engagement of the proline cycle for mitochondrial redox shuttling. With acquisition of effector functions, cells increasingly relied on glycolysis as opposed to oxidative phosphorylation, which was, however, not linked to changes in mitochondrial abundance. In exhaustion, decreased effector function concurred with a reduction in mitochondrial metabolism, glycolysis and amino acid import, and an upregulation of quiescence-associated genes, TXNIP and KLF2, and the T cell suppressive metabolites succinate and itaconate.DISCUSSION: Overall, these results identify multiple metabolic features that regulate quiescence, proliferation and effector function, but also exhaustion of CD8+ T cells during differentiation. Thus, targeting these metabolic checkpoints may be a promising therapeutic strategy for both prevention of exhaustion and promotion of stemness of anti-tumor T cells.PMID:37928527 | PMC:PMC10620935 | DOI:10.3389/fimmu.2023.1267816

IJU Case Rep. 2023 Sep 28;6(6):436-439. doi: 10.1002/iju5.12642. eCollection 2023 Nov.ABSTRACTINTRODUCTION: Early diagnosis of patients with urolithiasis or hypouricemia owing to inborn errors of hypoxanthine metabolism is important in preventing renal failure or drug-induced toxicity.CASE PRESENTATION: We identified three patients with xanthinuria using gas chromatography/mass spectrometry-based urine metabolomics: a 72-year-old male with bladder stone, a severe hypouricemic 59-year-old female with type 2 diabetes mellitus, and an 8-year and 9-month-old female who was first discovered to harbor a mutation in the xanthine dehydrogenase gene using whole-exome sequencing, but had a normal molybdenum cofactor sulfurase gene. Hydantoin-5-propionate was detected in the first and third patients but not in the second, suggesting that the first and second patients had type I and II xanthinuria, respectively.CONCLUSION: Gas chromatography/mass spectrometry-based metabolomics can be used for undiagnosed patients with xanthinuria, identification of the type of xanthinuria without allopurinol loading, and the quick functional evaluation of mutations in the xanthinuria-related genes.PMID:37928284 | PMC:PMC10622199 | DOI:10.1002/iju5.12642

Ecol Evol. 2023 Nov 2;13(11):e10667. doi: 10.1002/ece3.10667. eCollection 2023 Nov.ABSTRACTPlant and soil biodiversity can have significant effects on herbivore resistance mediated by plant metabolites. Here, we disentangled the independent effects of plant diversity and soil legacy on constitutive and herbivore-induced plant metabolomes of three plant species in two complementary microcosm experiments. First, we grew plants in sterile soil with three different plant diversity levels. Second, single plant species were grown on soil with different plant diversity-induced soil legacies. We infested a subset of all plants with Spodoptera exigua larvae, a generalist leaf-chewing herbivore, and assessed foliar and root metabolomes. Neither plant diversity nor soil legacy had significant effects on overall foliar, root, or herbivore-induced metabolome composition. Herbivore-induced metabolomes, however, differed from those of control plants. We detected 139 significantly regulated metabolites by comparing plants grown in monocultures with conspecifics growing in plant or soil legacy mixtures. Moreover, plant-plant and plant-soil interactions regulated 141 metabolites in herbivore-induced plants. Taken together, plant diversity and soil legacy independently alter the concentration and induction of plant metabolites, thus affecting the plant's defensive capability. This is a first step toward disentangling plant and soil biodiversity effects on herbivore resistance, thereby improving our understanding of the mechanisms that govern ecosystem functioning.PMID:37928199 | PMC:PMC10622854 | DOI:10.1002/ece3.10667

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