PubMed

J Agric Food Chem. 2023 Jul 27. doi: 10.1021/acs.jafc.3c00009. Online ahead of print.ABSTRACTHexanal is a phytochemical with antimicrobial activity. However, its antibacterial effect and mechanism against Vibrio parahaemolyticus (V. parahaemolyticus) remain unclear. The study aims to elucidate the associated mechanism using tandem mass tag quantitative proteomics and non-targeted metabolomics. Hexanal treatment reduced intracellular ATP concentration, increased membrane permeability, and destroyed the morphology and ultrastructure of V. parahaemolyticus cells. Proteomics and metabolomics data indicated that 572 differentially expressed proteins (DEPs) and 241 differential metabolites (DMs) were identified in hexanal-treated V. parahaemolyticus. These DEPs and DMs were involved in multiple biological pathways including amino acid metabolism, purine and pyrimidine biosynthesis, etc. Bioinformatics analysis revealed that hexanal damaged the structure and function of cell membranes, inhibited nucleotide metabolism, and disturbed carbohydrate metabolism and tricarboxylic acid cycle (TCA) cycle, which ultimately resulted in growth inhibition and bacterial death. The study is conducive to better understand the mode of action of hexanal against V. parahaemolyticus and offers experimental foundation for the application of hexanal as the antibacterial agent in the seafood-associated industry.PMID:37498004 | DOI:10.1021/acs.jafc.3c00009

Mov Disord. 2023 Jul 27. doi: 10.1002/mds.29566. Online ahead of print.ABSTRACTBACKGROUND: Glycoprotein nonmetastatic melanoma protein B (GPNMB) has been demonstrated to mediate pathogenicity in Parkinson's disease (PD) through interactions with α-synuclein, and plasma GPNMB tended to be a novel biomarker for PD.OBJECTIVE: The goal of this study was to investigate whether plasma GPNMB could act as a potential biomarker for the clinical diagnosis and severity monitoring of multiple system atrophy (MSA), another typical synucleinopathy.METHODS: Plasma GPNMB levels in patients with MSA, patients with PD, and healthy control subjects (HCs) were quantified using enzyme-linked immunosorbent assays.RESULTS: A total of 204 patients with MSA, 65 patients with PD, and 207 HCs were enrolled. The plasma GPNMB levels in patients with MSA were similar to those in HCs (P = 0.251) but were significantly lower than those in patients with PD (P = 0.003). Moreover, there was no significant correlation detected between the plasma GPNMB levels and disease severity scores of patients with MSA.CONCLUSIONS: No evidence was detected for the biomarker potential of plasma GPNMB in MSA. © 2023 International Parkinson and Movement Disorder Society.PMID:37497669 | DOI:10.1002/mds.29566

Food Funct. 2023 Jul 27. doi: 10.1039/d3fo01797d. Online ahead of print.ABSTRACTAsparagus is a perennial herb and is widely used as food and medicine in China. In this study, untargeted metabolomics analysis was applied to compare the chemical differences between the edible and inedible parts of asparagus, as well as the inedible parts of white and green asparagus. A total of 342 compounds were identified in the asparagus extracts, and 24 steroid saponins, 31 oxylipins and 36 LysoGPLs were identified for the first time in asparagus. Metabolomics analysis showed that the inedible part of white asparagus is rich in steroidal saponins, oxylipins and alkaloids, while the inedible part of green asparagus is rich in flavonoids, phenolic acids, LysoGPLs and amino acids. The inedible part of white asparagus showed significantly higher inhibitory effects on breast cancer 4T-1 cells than that of green asparagus. Network pharmacology analysis and molecular docking showed that the biological difference is related to higher levels of steroidal saponins and oxylipins in the inedible part of white asparagus. This study is useful for the wasted resource utilization of inedible parts of asparagus.PMID:37497633 | DOI:10.1039/d3fo01797d

J Proteome Res. 2023 Jul 27. doi: 10.1021/acs.jproteome.3c00382. Online ahead of print.ABSTRACTThe lipid metabolism adaptations of estrogen and progesterone receptor-positive breast cancer tumors from a mouse syngeneic model are investigated in relation to differences across the transition from hormone-dependent (HD) to hormone-independent (HI) tumor growth and the acquisition of endocrine therapy (ET) resistance (HIR tumors). Results are articulated with reported polar metabolome results to complete a metabolic picture of the above transitions and suggest markers of tumor progression and aggressiveness. Untargeted nuclear magnetic resonance metabolomics was used to analyze tumor and mammary tissue lipid extracts. Tumor progression (HD-HI-HIR) was accompanied by increased nonesterified cholesterol forms and phospholipids (phosphatidylcholine, phosphatidylethanolamine, sphingomyelins, and plasmalogens) and decreased relative contents of triglycerides and fatty acids. Predominating fatty acids became shorter and more saturated on average. These results were consistent with gradually more activated cholesterol synthesis, β-oxidation, and phospholipid biosynthesis to sustain tumor growth, as well as an increase in cholesterol (possibly oxysterol) forms. Particular compound levels and ratios were identified as potential endocrine tumor HD-HI-HIR progression markers, supporting new hypotheses to explain acquired ET resistance.PMID:37497607 | DOI:10.1021/acs.jproteome.3c00382

Int J Biol Sci. 2023 Jul 9;19(11):3576-3594. doi: 10.7150/ijbs.85133. eCollection 2023.ABSTRACTIncreasing evidence suggests that immunometabolism has started to unveil the role of metabolism in shaping immune function and autoimmune diseases. In this study, our data show that purinergic receptor P2Y12 (P2RY12) is highly expressed in concanavalin A (ConA)-induced immune hepatitis mouse model and serves as a potential metabolic regulator in promoting metabolic reprogramming from oxidative phosphorylation to glycolysis in T cells. P2RY12 deficiency or inhibition of P2RY12 with P2RY12 inhibitors (clopidogrel and ticagrelor) are proved to reduce the expression of inflammatory mediators, cause CD4+ and CD8+ effector T cells hypofunction and protect the ConA-induced immune hepatitis. A combined proteomics and metabolomics analysis revealed that P2RY12 deficiency causes redox imbalance and leads to reduced aerobic glycolysis by downregulating the expression of hexokinase 2 (HK2), a rate-limiting enzyme of the glycolytic pathway, indicating that HK2 might be a promising candidate for the treatment of diseases associated with T cell activation. Further analysis showed that P2RY12 prevents HK2 degradation by activating the PI3K/Akt pathway and inhibiting lysosomal degradation. Our findings highlight the importance of the function of P2RY12 for HK2 stability and metabolism in the regulation of T cell activation and suggest that P2RY12 might be a pivotal regulator of T cell metabolism in ConA-induced immune hepatitis.PMID:37497007 | PMC:PMC10367548 | DOI:10.7150/ijbs.85133

Heliyon. 2023 Jul 8;9(7):e18045. doi: 10.1016/j.heliyon.2023.e18045. eCollection 2023 Jul.ABSTRACTParkinson's disease (PD) is the second most common neurodegenerative disease, with an increasing prevalence as the population ages, posing a serious threat to human health, but the pathogenesis remains uncertain. Acanthopanax senticosus (Rupr. et Maxim.) Harms (ASH) (aqueous ethanol extract), a Chinese herbal medicine, provides obvious and noticeable therapeutic effects on PD. To further investigate the ASH's mechanism of action in treating PD, the structural and functional gut microbiota, as well as intestinal metabolite before and after ASH intervention in the PD mice model, were examined utilizing metagenomics and fecal metabolomics analysis. α-syn transgenic mice were randomly divided into a model and ASH groups, with C57BL/6 mice as a control. The ASH group was gavaged with ASH (45.5 mg/kg/d for 20d). The time of pole climbing and autonomous activity were used to assess motor ability. The gut microbiota's structure, composition, and function were evaluated using Illumina sequencing. Fecal metabolites were identified using UHPLC-MS/MS to construct intestinal metabolites. The findings of this experiment demonstrate that ASH may reduce the climbing time of PD model mice while increasing the number of autonomous movements. The results of metagenomics analysis revealed that ASH could up-regulated Firmicutes and down-regulated Actinobacteria at the phylum level, while Clostridium was up-regulated and Akkermansia was down-regulated at the genus level; it could also recall 49 species from the phylum Firmicutes, Actinobacteria, and Tenericutes. Simultaneously, metabolomics analysis revealed that alpha-Linolenic acid metabolism might be a key metabolic pathway for ASH to impact in PD. Furthermore, metagenomics function analysis and metabolic pathway enrichment analysis revealed that ASH might influence unsaturated fatty acid synthesis and purine metabolism pathways. These metabolic pathways are connected to ALA, Palmitic acid, Adenine, and 16 species of Firmicutes, Actinobacteria, and Tenericutes. Finally, these results indicate that ASH may alleviate the movement disorder of the PD model, which may be connected to the regulation of gut microbiota structure and function as well as the modulation of metabolic disorders by ASH.PMID:37496895 | PMC:PMC10366437 | DOI:10.1016/j.heliyon.2023.e18045

Front Plant Sci. 2023 Jul 11;14:1216826. doi: 10.3389/fpls.2023.1216826. eCollection 2023.ABSTRACTSweet orange 'Newhall' (C. sinensis) is a popular fruit in high demand all over the world. Its peel and pulp are rich in a variety of nutrients and are widely used in catering, medicine, food and other industries. Grafting is commonly practiced in citrus production. Different rootstock types directly affect the fruit quality and nutritional flavor of citrus. However, the studies on citrus metabolites by grafting with different rootstocks are very limited, especially for amino acids (AAs). The preliminary test showed that there were significant differences in total amino acid content of two rootstocks (Poncirus trifoliata (CT) and C. junos Siebold ex Tanaka (CJ)) after grafting, and total amino acid content in the peel was higher than flesh. However, the molecular mechanism affecting amino acid differential accumulation remains unclear. Therefore, this study selected peel as the experimental material to reveal the amino acid components and differential accumulation mechanism of sweet orange 'Newhall' grafted with different rootstocks through combined transcriptome and metabolome analysis. Metabolome analysis identified 110 amino acids (AAs) and their derivatives in sweet orange 'Newhall' peels, with L-valine being the most abundant. L-asparagine was observed to be affected by both developmental periods and rootstock grafting. Weighted gene co-expression network analysis (WGCNA) combined with Redundancy Analysis (RDA) revealed eight hub structural genes and 41 transcription factors (TFs) that significantly influenced amino acid biosynthesis in sweet orange 'Newhall' peels. Our findings further highlight the significance of rootstock selection in enhancing the nutritional value of citrus fruits and might contribute to the development of functional citrus foods and nutritional amino acid supplements.PMID:37496860 | PMC:PMC10366444 | DOI:10.3389/fpls.2023.1216826

Evid Based Complement Alternat Med. 2023 Jul 18;2023:9693390. doi: 10.1155/2023/9693390. eCollection 2023.ABSTRACTOBJECTIVE: The aim of the study is to investigate the serum metabolomics of electroacupuncture (EA) with different current intensities in the treatment of functional constipation (FC).METHODS: The total number of FC patients was 19, (7, 6, 6, in the low current intensity group (LCI), high current intensity group (HCI), and mosapride citrate tablet control group (MC), respectively). Patients in the EA groups received 16 sessions of acupuncture treatments. Patients in the MC group were orally administered 5 mg mosapride citrate tablets 3 times daily, and serum samples were collected from the patients before and after treatment. Orthogonal partial least square-discriminant analysis (OPLS-DA) was used to assess the metabolic data. The significant differences before and after FC treatment are shown in the OPLS-DA score plot. Variable importance plots (VIPs) and T tests were used to identify significant metabolites.RESULTS: Among the three groups, the number of metabolites with VIP > 1 was 11, 7, and 21 (in LCI, HCI and MC groups, respectively). Compared with those before treatment, the serum metabolites of patients were characterized by increased levels of L-ornithine (p < 0.05) and glyceric acid in the LCI group (p < 0.05), increased levels of vanillic acid in the MC group (p < 0.05), and decreased levels of arabinonic acid in the MC group (p < 0.05).CONCLUSIONS: The effects of EA treatment on the serum metabolomics of FC may involve fatty acid and amino acid metabolism.PMID:37496821 | PMC:PMC10368503 | DOI:10.1155/2023/9693390

Infect Drug Resist. 2023 Jul 20;16:4741-4754. doi: 10.2147/IDR.S411658. eCollection 2023.ABSTRACTBACKGROUND: The issue of methicillin-resistant Staphylococcus aureus (MRSA) resistant to many antibiotics and causing serious infectious diseases is a growing healthcare concern.PURPOSE: In recent years, exogenous administration of metabolites in combination with antibiotics can re-sensitize resistant bacteria to antibiotics; however, their effects vary, and their underlying mechanism of action remains elusive.METHODS: We assessed the bactericidal effects of the three amino acids in combination with gentamicin in vitro and in vivo. Subsequently, we explored the role of these amino acids on the metabolomics of MRSA using Liquid chromatography-tandem mass spectrometry (LC-MS/MS). Furthermore, we performed the downstream analyses using MetaboAnalyst and Interactive Pathways Explorer.RESULTS: Exogenous threonine showed the best bactericidal efficacy with gentamicin, followed by glycine, wherein serine had no effect. Amino acid treatments mainly up-regulated the metabolites, increased the amino acid abundance, and significantly activated metabolisms; these effects were consistent with the bactericidal efficacy of the three amino acids. Most amino acids participated in the tricarboxylic acid cycle, and threonine supplementation increased the activities of citrate synthase, isocitrate dehydrogenase and α-ketoglutarate dehydrogenase, whereas glycine increased activities of citrate synthase and α-ketoglutarate dehydrogenase, and serine did not affect the activities of any of the three key enzymes. We identified 24 biomarkers in the three groups, among which glutamic acid and cysteine showed a gradient decrease and increase, respectively. Subsequent analyses revealed that glutamic acid but not cysteine promoted the bactericidal effect of gentamicin synergistically.CONCLUSION: Threonine has the best synergistic effect in reversing bacterial resistance compared to glycine and serine. We show that different amino acids combined with an antibiotic mainly affect amino acid metabolism and act via different metabolic regulatory mechanisms, which could help develop effective strategies for tackling MRSA infections.PMID:37496695 | PMC:PMC10366528 | DOI:10.2147/IDR.S411658

iScience. 2023 Jun 19;26(7):107181. doi: 10.1016/j.isci.2023.107181. eCollection 2023 Jul 21.ABSTRACTNeutrophils are potent immune cells with key antimicrobial functions. Previous in vitro work has shown that neutrophil effector functions are mainly fueled by intracellular glycolysis. Little is known about the state of neutrophils still in the circulation in patients during infection. Here, we combined flow cytometry, stimulation assays, transcriptomics, and metabolomics to investigate the link between inflammatory and metabolic pathways in blood neutrophils of patients with community-acquired pneumonia. Patients' neutrophils, relative to neutrophils from age- and sex- matched controls, showed increased degranulation upon ex vivo stimulation, and portrayed distinct upregulation of inflammatory transcriptional programs. This neutrophil phenotype was accompanied by a high-energy state with increased intracellular ATP content, and transcriptomic and metabolic upregulation of glycolysis and glycogenolysis. One month after hospital admission, these metabolic and transcriptomic changes were largely normalized. These data elucidate the molecular programs that underpin a balanced, yet primed state of blood neutrophils during pneumonia.PMID:37496676 | PMC:PMC10366455 | DOI:10.1016/j.isci.2023.107181

Biomed Chromatogr. 2023 Jul 26:e5704. doi: 10.1002/bmc.5704. Online ahead of print.ABSTRACTWaste medicinal plants are widely used in drug production. With the increasing demand for botanical drugs, there is an urgent need to identify new and effective drugs and improve the utilization of medicinal plant resources. Wuteng tablets (WTP) are extracted from the stem of Schisandra chinensis and have a good therapeutic effect on Alzheimer's disease. In this study, a holistic identification strategy based on UHPLC-Q/TOF-MS was developed for the first time to investigate the metabolites and metabolic pathways involved in the in vitro metabolism and liver microsomal incubation and in the in vivo metabolic system of rats after WTP administration. After the oral administration of WTP, 21 metabolites were identified in the serum and 25 metabolites were identified in the urine, of which six were new metabolites; 33 metabolites were inferred from the microsomal metabolites in vitro. The metabolic pathways related to WTP mainly involve demethylation, hydroxylation, dehydroxylation and dehydrogenation. In this study, the metabolites and metabolic pathways of WTP were elucidated via UHPLC-Q/TOF-MS, which provided a basis for an in-depth study of the pharmacodynamic and pharmacotoxicological effects of WTP.PMID:37496363 | DOI:10.1002/bmc.5704

Biomed Chromatogr. 2023 Jul 26:e5707. doi: 10.1002/bmc.5707. Online ahead of print.ABSTRACTHyperlipidemia is a chronic metabolic disorder characterized by alterations in lipid metabolism as well as other pathways. Laportea bulbifera, an indigenous medicinal plant of Chinese herbal medicine, exhibits therapeutic effects on hyperlipidemia, but the mechanisms remain unclear. This study investigated the potential mechanisms underlying the anti-hyperlipidemic effects of L. bulbifera using an integrated strategy based on metabolomics and network pharmacology methods that were established to investigate the potential mechanism of anti-hyperlipidemia effect of L. bulbifera. First, the therapeutic effects of L. bulbifera on body weight reduction and biochemical indices were assessed. Next, 18 significant metabolites distinguishing the control and model groups were identified based on serum metabolomics and multivariate analyses. Then, a compound-target network was constructed by linking L. bulbifera and hyperlipidemia using network pharmacology. Three metabolic pathways involved in treating hyperlipidemia were identified. Finally, five crucial targets were selected by constructing a bionetwork starting from the compounds and ending in the metabolites. This study established an integrated strategy based on metabolomics coupled with network pharmacology and revealed the mechanism underlying the protective effects of L. bulbifera against hyperlipidemia for the first time.PMID:37496197 | DOI:10.1002/bmc.5707

Thorax. 2023 Jul 26:thoraxjnl-2021-217923. doi: 10.1136/thorax-2021-217923. Online ahead of print.ABSTRACTBACKGROUND: Diet has a crucial role in the gut microbiota, and dysbiosis in the gut and lungs has been suggested to be associated with chronic obstructive pulmonary disease. We compared the diet, microbiome and metabolome between asymptomatic smokers and those with emphysema.METHODS: We enrolled 10 asymptomatic smokers with preserved lung function and 16 smokers with emphysema with severe airflow limitation. Dietary intake information was gathered by a self-reported questionnaire. Sputum and faecal samples were collected for microbial and metabolomics analysis. A murine model of emphysema was used to determine the effect of metabolite supplementation.RESULTS: Despite having a similar smoking history with emphysema patients, asymptomatic smokers had higher values of body mass index, fibre intake and faecal acetate level. Linear discriminant analysis identified 17 microbial taxonomic members that were relatively enriched in the faeces of asymptomatic smokers. Analysis of similarity results showed dissimilarity between the two groups (r=0.287, p=0.003). Higher acetate level was positively associated with forced expiratory volume in one second in the emphysema group (r=0.628, p=0.012). Asymptomatic smokers had a greater number of species associated with acetate and propionate (r>0.6) than did those with emphysema (30 vs 19). In an emphysema mouse model, supplementation of acetate and propionate reduced alveolar destruction and the production of proinflammatory cytokines, and propionate decreased the CD3+CD4+IL-17+ T-cell population in the lung and spleen.CONCLUSION: Smokers with emphysema showed differences in diet, microbiome and short-chain fatty acids compared with asymptomatic smokers. Acetate and propionate showed therapeutic effects in a smoking-induced murine model of emphysema.PMID:37495367 | DOI:10.1136/thorax-2021-217923

Bioresour Technol. 2023 Jul 24:129486. doi: 10.1016/j.biortech.2023.129486. Online ahead of print.ABSTRACTBioethanol recovery from food waste through high solids enzymatic hydrolysis (HSEH) and high solids bioethanol fermentation (HSBF) alleviate the energy crisis. However, this cause decreased glucose and bioethanol yields due to the high solids content. In this study, saponin was introduced into food waste HSEH and HSBF systems to enhance the product yields. Under the regulation of saponin, the substrate released >90% of the theoretical reducing sugar. The glucose concentration increased by 137.41 g/L after 24 h of HSEH with 2.0% saponin. The bioethanol titer reached 73.2 g/L (1.0%-saponin). Untargeted metabolomics illustrating that saponin had higher antifungal properties at lower concentrations (0.5%-saponin) that caused a decrease in bioethanol yield. The addition of saponin concentrations of 1.0%∼3.0% promoted HSEH, HSBF, and the metabolism of Saccharomyces cerevisiae; thus, 1.0% was suggested for practical use. This study deepened the understanding of saponin in enhancing HSBF and provides theoretical support for further application.PMID:37495159 | DOI:10.1016/j.biortech.2023.129486

Sci Total Environ. 2023 Jul 24:165780. doi: 10.1016/j.scitotenv.2023.165780. Online ahead of print.ABSTRACTBACKGROUND: Short-term exposure to air pollution has been reported to be associated with cardiopulmonary diseases, but the underlying mechanisms remain unclear. This study aimed to investigate changes in serum metabolites associated with immediate, short- and medium-term exposures to ambient air pollution.METHODS: We used data from the German population-based Cooperative Health Research in the Region of Augsburg (KORA) S4 survey (1999-2001) and two follow-up examinations (F4: 2006-08 and FF4: 2013-14). Mass-spectrometry-based targeted metabolomics was used to quantify metabolites among serum samples. Only participants with repeated metabolites measurements were included in this analysis. We collected daily averages of fine particles (PM2.5), coarse particles (PMcoarse), nitrogen dioxide (NO2), and ozone (O3) at urban background monitors located in Augsburg, Germany. Covariate-adjusted generalized additive mixed-effects models were used to examine the associations between immediate (2-day average of same day and previous day as individual's blood withdrawal), short- (2-week moving average), and medium-term exposures (8-week moving average) to air pollution and metabolites. We further performed pathway analysis for the metabolites significantly associated with air pollutants in each exposure window.RESULTS: Of 9620 observations from 4261 study participants, we included 5772 (60.0 %) observations from 2583 (60.6 %) participants in this analysis. Out of 108 metabolites that passed quality control, multiple significant associations between metabolites and air pollutants with several exposure windows were identified at a Bonferroni corrected p-value threshold (p < 3.9 × 10-5). We found the highest number of associations for NO2, particularly at the medium-term exposure windows. Among the identified metabolic pathways based on the metabolites significantly associated with air pollutants, the glycerophospholipid metabolism was the most robust pathway in different air pollutants exposures.CONCLUSIONS: Our study suggested that short- and medium-term exposure to air pollution might induce alterations of serum metabolites, particularly in metabolites involved in metabolic pathways related to inflammatory response and oxidative stress.PMID:37495154 | DOI:10.1016/j.scitotenv.2023.165780

J Heart Lung Transplant. 2023 Jul 24:S1053-2498(23)01940-X. doi: 10.1016/j.healun.2023.07.009. Online ahead of print.ABSTRACTBACKGROUND: One-carbon metabolism supports the activation, proliferation, and function of multiple immune cells. However, researchers have not clearly determined whether and how one-carbon metabolic enzymes contribute to heart transplant rejection.METHODS: We investigated the dynamic metabolic adaptation in grafts during heart transplant rejection by conducting transcriptomics, metabolomics and single-cell RNA sequencing studies of cardiac tissue from human and mouse heart transplant recipients. We also assessed the expression of the one-carbon metabolic enzyme MTHFD2 in cardiac grafts by immunofluorescence and flow cytometry assays. Then we constructed a murine heart transplant model with T cell-specific Mthfd2 knockout mice, analyzed T cells function by flow cytometry assays and enzyme-linked immunospot assays, and studied the mechanism by Cleavage Under Targets and Tagmentation assays. Finally, we studied the effect of a pharmacological inhibitor of MTHFD2 in humanized skin transplant model.RESULTS: We revealed that the one-carbon metabolism enzyme MTHFD2 was a hallmark of alloreactive T cells and was linked to T cell proliferation and function after exposure to alloantigen. And, Mthfd2 ablation prevented murine heart transplant rejection. Mechanistically, we found Mthfd2 ablation affected the IRF4/PD-1 pathway through a metabolic-epigenetic mechanism involving H3K4me3. Furthermore, we found that inhibiting MTHFD2 attenuated human allograft rejection in a humanized skin transplant model.CONCLUSIONS: These data show that the one-carbon metabolic enzyme MTHFD2 serves as a metabolic checkpoint of alloreactive T cells and suggest that it may be a potential therapeutic target for heart transplant rejection.PMID:37495036 | DOI:10.1016/j.healun.2023.07.009

Respir Med. 2023 Jul 24:107369. doi: 10.1016/j.rmed.2023.107369. Online ahead of print.ABSTRACTBACKGROUND: As an important place of material exchange, the homeostasis of the pulmonary circulation environment and function lays an essential foundation for the normal execution of various physiological functions of the body. Small metabolic molecules in the circulation can reflect the corresponding state of the pulmonary circulation.METHODS: We enrolled patients with Patent Foramen Ovale and obtained blood from the pulmonary arteries and veins through heart catheterization. UPLC-MS based untargeted metabolomics was used to compare the changes and metabolic differences of plasma between pulmonary vein and pulmonary artery.RESULTS: The plasma metabolomics revealed that pulmonary artery had a different metabolomic profile compared to venous. 1060 metabolites were identified, and 61 metabolites were differential metabolites. Purine, Amino acids, Nicotinamide, Tetradecanedioic acid and Bile acid were the most markedly.CONCLUSION: The differential metabolites are mostly related to immune inflammation and damage repaired. It is suggested that the pulmonary circulation is always in a steady state of injury and repair while pathological changes may be triggered when the homeostasis is broken. These changes play an important role in revealing the development process and etiology of lung homeostasis and related diseases. Relevant metabolites can be used as potential targets for further study of pulmonary circulation homeostasis.PMID:37494975 | DOI:10.1016/j.rmed.2023.107369

Redox Biol. 2023 Jul 20;65:102822. doi: 10.1016/j.redox.2023.102822. Online ahead of print.ABSTRACTFerroptosis has emerged to be a promising approach in cancer therapies; however, colorectal cancer (CRC) is relatively insensitive to ferroptosis. Exactly how the gut microenvironment impacts the ferroptotic sensitivity of CRC remains unknown. Herein, by performing metabolomics, we discovered that butyrate concentrations were significantly decreased in CRC patients. Butyrate supplementation sensitized CRC mice to ferroptosis induction, showing great in vivo translatability. Particularly, butyrate treatment reduced ferroptotic resistance of cancer stem cells. Mechanistically, butyrate inhibited xCT expression and xCT-dependent glutathione synthesis. Moreover, we identified c-Fos as a novel xCT suppressor, and further elucidated that butyrate induced c-Fos expression via disrupting class I HDAC activity. In CRC patients, butyrate negatively correlated with tumor xCT expression and positively correlated with c-Fos expression. Finally, butyrate was found to boost the pro-ferroptotic function of oxaliplatin (OXA). Immunohistochemistry data showed that OXA non-responders exhibited higher xCT expression compared to OXA responders. Hence, butyrate supplementation is a promising approach to break the ferroptosis resistance in CRC.PMID:37494767 | DOI:10.1016/j.redox.2023.102822

BMC Microbiol. 2023 Jul 26;23(1):198. doi: 10.1186/s12866-023-02942-6.ABSTRACTBACKGROUND: Acanthamoeba castellanii is a free-living protist that feeds on diverse bacteria. A. castellanii has frequently been utilized in studies on microbial interactions. Grazing bacteria also exhibit diverse effects on the physiological characteristics of amoebae, such as their growth, encystation, and cytotoxicity. Since the composition of amoebae amino acids is closely related to cellular activities, it can indicate the overall responses of A. castellanii to various stimuli.METHOD: A. castellanii was exposed to different culture conditions in low-nutrient medium with heat-killed DH5α to clarify their effects. A targeted metabolomic technique was utilized to evaluate the concentration of cellular amino acids. The amino acid composition and pathways were analyzed by two web-based tools: MetaboAnalyst and Pathview. Then, long-term exposure to A. castellanii was investigated through in silico and in vitro methods to elucidate the homeostasis of amino acids and the growth of A. castellanii.RESULTS: Under short-term exposure, all kinds of amino acids were enriched in all exposed groups. In contrast to the presence of heat-killed bacteria, the medium exhibited obvious effects on the amino acid composition of A. castellanii. After long-term exposure, the amino acid composition was more similar to that of the control group. A. castellanii may achieve amino acid homeostasis through pathways related to alanine, aspartate, citrulline, and serine.DISCUSSION: Under short-term exposure, compared to the presence of bacteria, the type of medium exerted a more powerful effect on the amino acid composition of the amoeba. Previous studies focused on the interaction of the amoeba and bacteria with effective secretion systems and effectors. This may have caused the effects of low-nutrient environments to be overlooked.CONCLUSION: When A. castellanii was stimulated in the coculture system through various methods, such as the presence of bacteria and a low-nutrient environment, it accumulated intracellular amino acids within a short period. However, different stimulations correspond to different amino acid compositions. After long-term exposure, A. castellanii achieved an amino acid equilibrium by downregulating the biosynthesis of several amino acids.PMID:37495951 | DOI:10.1186/s12866-023-02942-6

BMC Microbiol. 2023 Jul 26;23(1):199. doi: 10.1186/s12866-023-02927-5.ABSTRACTBACKGROUND: Intestinal flora has been proposed to mediate the occurrence of postmenopausal osteoporosis (PMO). However, the mechanism by which microbes and their metabolites interactively promote PMO remains unknown.METHODS: This study aimed to investigate changes in the intestinal flora and associated metabolites, and their role in PMO. 16S rRNA gene sequencing and metabolomics were performed to obtain postmenopausal women with osteopenia (lower bone mass, LBM), postmenopausal women with osteoporosis (OST), and healthy women as the control group.RESULTS: We identified taxa-specific and metabolite differences in the intestinal flora of the participants of this study. The pathogenic bacteria Klebsiella (0.59% and 0.71%, respectively) and Escherichia-Shigella (2.72% and 4.30%, respectively) were enriched in the LBM and OST groups (p < 0.05). Some short-chain fatty acid (SCFAs) producing bacteria, Lactobacillus, Akkermansia, Prevotella, Alistipes, and Butyricicoccus, were reduced in patients with LBM and OST compared to the control. Moreover, fecal metabolomic analyses suggested that the metabolites of indole-3-acetic acid and 7-ketodeoxycholic acid were altered in the LBM and OST groups compared to the control (p < 0.05). Enrichment analysis suggested that valine, leucine, and isoleucine biosynthesis; aromatic amino acid biosynthesis; and phenylalanine metabolism were significantly associated with the identified microbiota biomarkers and OST. Moreover, metabolite marker signatures distinguished patients in the OST from those in the control group with an area under the curve (AUC) of 0.978 and 1.00 in the negative and positive ion modes, respectively. Finally, we also found that the fecal level of interleukin-10 (IL-10) in the OST group was significantly lower than that in the control group and LBM group (p < 0.05), while tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were significantly higher in the OST group than that in the control group (p < 0.05).CONCLUSIONS: This study provides robust evidence connecting the intestinal flora and fecal metabolomics with PMO. Integrated metabolite and microbiota analyses demonstrated that in addition to dysregulated bacteria, indole-3-acetic acid, 7-ketodeoxycholic acid, and other metabolites can be used for the distinguish of LBM and PMO.PMID:37495941 | DOI:10.1186/s12866-023-02927-5