PubMed

Clin Nutr. 2023 Sep 25;42(11):2214-2228. doi: 10.1016/j.clnu.2023.09.021. Online ahead of print.ABSTRACTBACKGROUND & AIMS: Acute myeloid leukaemia (AML) chemotherapy has been reported to impact gut microbiota composition. In this study, we investigated using a multi -omics strategy the changes in the gut microbiome induced by AML intense therapy and their association with gut barrier function and cachectic hallmarks.METHODS: 10 AML patients, allocated to standard induction chemotherapy (SIC), were recruited. Samples and data were collected before any therapeutic intervention (T0), at the end of the SIC (T1) and at discharge (T4). Gut microbiota composition and function, markers of inflammation, metabolism, gut barrier function and cachexia, as well as faecal, blood and urine metabolomes were assessed.RESULTS: AML patients demonstrated decreased appetite, weight loss and muscle wasting during hospitalization, with an incidence of cachexia of 50%. AML intensive treatment transiently impaired the gut barrier function and led to a long-lasting change of gut microbiota composition characterized by an important loss of diversity. Lactobacillaceae and Campylobacter concisus were increased at T1 while Enterococcus faecium and Staphylococcus were increased at T4. Metabolomics analyses revealed a reduction in urinary hippurate and faecal bacterial amino acid metabolites (bAAm) (2-methylbutyrate, isovalerate, phenylacetate). Integration using DIABLO revealed a deep interconnection between all the datasets. Importantly, we identified bacteria which disappearance was associated with impaired gut barrier function (Odoribacter splanchnicus) and body weight loss (Gemmiger formicilis), suggesting these bacteria as actionable targets.CONCLUSION: AML intensive therapy transiently impairs the gut barrier function while inducing enduring alterations in the composition and metabolic activity of the gut microbiota that associate with body weight loss.TRIAL REGISTRATION: NCT03881826, https://clinicaltrials.gov/ct2/show/NCT03881826.PMID:37806074 | DOI:10.1016/j.clnu.2023.09.021

Aquat Toxicol. 2023 Sep 26;264:106707. doi: 10.1016/j.aquatox.2023.106707. Online ahead of print.ABSTRACTSertraline is an environmental pollutant which received magnified scientific attention due to its global presence in waters. Adverse effects on feeding, reproduction and other traits were observed mostly in unstressed aquatic organisms. Chronic stress, however, induces significant physiological changes, and the effects of sertraline in stressed fish may differ from those observed in non-stressed individuals. The current laboratory study addresses this gap by repeatedly monitoring the individual aggression of chronically stressed juvenile chub (Squalius cephalus L.) using the non-reversing mirror test at an environmental sertraline concentration of 0.022 g/L every three to four days for a period of 39 days. Specifically, it was hypothesized that the level and repeatability of aggressiveness would be (i) correlated with the concentration of sertraline/norsertraline in the fish brain; (ii) linked to the individual brain metabolomic profile described by LC-HRMS analyses; (iii) related to the lunar cycle. Sertraline led to an increase in fish aggression and more repeatable/consistent behaviour compared to control fish. While the level of sertraline in the brain did not correlate with aggressiveness, aggressive responses increased with higher norsertraline concentration. The observed aggressive behaviour also varied depending on the individual metabolomic profile of the brain. The behavioural outcome and metabolic change in fish brain may indicate that sertraline has demonstrated neuroprotective effects by reducing cortisol release. It is possible that fish exposed to sertraline could suffer a blunted stress response under the chronic stressors in the wild. Aggressiveness of both treatments evolved in time, revealing a sinusoid-like pattern corresponding to a lunar cycle with a peak of the aggressiveness during the new moon. There is a need for future studies to focus on this relationship to reveal its details and general validity. Our results emphasize that long-term behavioural variability should generally be taken into account in laboratory behavioural studies.PMID:37806025 | DOI:10.1016/j.aquatox.2023.106707

Microb Cell Fact. 2023 Oct 8;22(1):204. doi: 10.1186/s12934-023-02221-z.ABSTRACTBACKGROUND: "ATP wasting" has been observed in 13C metabolic flux analyses of Saccharomyces cerevisiae, a yeast strain commonly used to produce ethanol. Some strains of S. cerevisiae, such as the sake strain Kyokai 7, consume approximately two-fold as much ATP as laboratory strains. Increased ATP consumption may be linked to the production of ethanol, which helps regenerate ATP.RESULTS: This study was conducted to enhance ethanol and 2,3-butanediol (2,3-BDO) production in the S. cerevisiae strains, ethanol-producing strain BY318 and 2,3-BDO-producing strain YHI030, by expressing the fructose-1,6-bisphosphatase (FBPase) and ATP synthase (ATPase) genes to induce ATP dissipation. The introduction of a futile cycle for ATP consumption in the pathway was achieved by expressing various FBPase and ATPase genes from Escherichia coli and S. cerevisiae in the yeast strains. The production of ethanol and 2,3-BDO was evaluated using high-performance liquid chromatography and gas chromatography, and fermentation tests were performed on synthetic media under aerobic conditions in batch culture. The results showed that in the BY318-opt_ecoFBPase (expressing opt_ecoFBPase) and BY318-ATPase (expressing ATPase) strains, specific glucose consumption was increased by 30% and 42%, respectively, and the ethanol production rate was increased by 24% and 45%, respectively. In contrast, the YHI030-opt_ecoFBPase (expressing opt_ecoFBPase) and YHI030-ATPase (expressing ATPase) strains showed increased 2,3-BDO yields of 26% and 18%, respectively, and the specific production rate of 2,3-BDO was increased by 36%. Metabolomic analysis confirmed the introduction of the futile cycle.CONCLUSION: ATP wasting may be an effective strategy for improving the fermentative biosynthetic capacity of S. cerevisiae, and increased ATP consumption may be a useful tool in some alcohol-producing strains.PMID:37807050 | DOI:10.1186/s12934-023-02221-z

Trends Immunol. 2023 Oct 6:S1471-4906(23)00204-1. doi: 10.1016/j.it.2023.09.008. Online ahead of print.ABSTRACTDietary fibers, including chitin, have a major impact on gastrointestinal (GI) physiology and immunity. Two recent articles, by Parrish et al. and Kim et al., credit depletion of dietary fibers or supplementation with chitin, with negative and positive effects, respectively, on the immune system of the murine digestive tract. This has relevant implications for food allergies and systemic metabolism.PMID:37806931 | DOI:10.1016/j.it.2023.09.008

Georgian Med News. 2023 Jul-Aug;(340-341):275-279.ABSTRACTEndometriosis is a widespread pathology among women of reproductive age. The pathophysiological mechanisms of the disease aren't enough understood yet. In addition, the "gold" standard of diagnosis is still laparoscopy. Worldwide, patients may experience a delay in the diagnosis of endometriosis by approximately 6 to 12 years. Aim of the study - to conduct a systematic analysis of the data presented in modern literature on the metabolomic diagnosis of endometriosis in general and endometrioid cystadenomas in particular. The review includes data from world studies over the past 7 years regarding metabolomic screening for endometriosis. Metabolomic changes characteristic of endometriosis, noted in the metabolism of amino acids, organic acids, lipids, purines, are presented. The described disorders reflect the processes of oxidative stress, mitochondrial dysfunction, endothelial dysfunction, and active angiogenesis. The identified metabolomic changes may improve and speed up the process of diagnosing endometriosis in general and endometrioid cystadenomas in particular in a non-invasive way. Certain detailed violations of metabolic processes can become a promising point of application for the correction of symptoms and the treatment of this pathology.PMID:37805911

Food Res Int. 2023 Nov;173(Pt 2):113488. doi: 10.1016/j.foodres.2023.113488. Epub 2023 Sep 17.ABSTRACTHongqu rice wine, a famous traditional fermented alcoholic beverage, is brewed with traditional Hongqu (mainly including Gutian Qu and Wuyi Qu). This study aimed to compare the microbial communities and metabolic profiles in the traditional brewing of Hongqu rice wines fermented with Gutian Qu and Wuyi Qu. Compared with Hongqu rice wine fermented with Wuyi Qu (WY), Hongqu rice wine fermented with Gutian Qu (GT) exhibited higher levels of biogenic amines. The composition of volatile flavor components of Hongqu rice wine brewed by different fermentation starters (Gutian Qu and Wuyi Qu) was obviously different. Among them, ethyl acetate, isobutanol, 3-methylbutan-1-ol, ethyl decanoate, ethyl palmitate, ethyl oleate, nonanoic acid, 4-ethylguaiacol, 5-pentyldihydro-2(3H)-furanone, ethyl acetate, n-decanoic acid etc. were identified as the characteristic aroma-active compounds between GT and WY. Microbiome analysis based on high-throughput sequencing of full-length 16S rDNA/ITS-5.8S rDNA amplicons revealed that Lactococcus, Leuconostoc, Pseudomonas, Serratia, Enterobacter, Weissella, Saccharomyces, Monascus and Candida were the predominant microbial genera during the traditional production of GT, while Lactococcus, Lactobacillus, Leuconostoc, Enterobacter, Kozakia, Weissella, Klebsiella, Cronobacter, Saccharomyces, Millerozyma, Monascus, Talaromyces and Meyerozyma were the predominant microbial genera in the traditional fermentation of WY. Correlation analysis revealed that Lactobacillus showed significant positive correlations with most of the characteristic volatile flavor components and biogenic amines. Furthermore, bioinformatical analysis based on PICRUSt revealed that microbial enzymes related to biogenic amines synthesis were more abundant in GT than those in WY, and the enzymes responsible for the degradation of biogenic amines were less abundant in GT than those in WY. Collectively, this study provides important scientific data for enhancing the flavor quality of Hongqu rice wine, and lays a solid foundation for the healthy and sustainable development of Hongqu rice wine industry.PMID:37803808 | DOI:10.1016/j.foodres.2023.113488

Environ Res. 2023 Oct 5:117310. doi: 10.1016/j.envres.2023.117310. Online ahead of print.ABSTRACTDeciphering the vertical connectivity of oceanic microbiome and metabolome is crucial for understanding the carbon sequestration and achieving the carbon neutrality. However, we lack a systematic view of the interplay among particle transport, microbial community, and metabolic trait across depths. Through integrating the biogeochemical, microbial, and metabolic characteristics of a deep cold-seep water column (∼1989 m), we find the altered connectivity of microbial community and dissolved organic matter (DOM) across depths. Both the microbial communities (bacteria and protists) and DOM show a clear compositional connectivity from surface to the depth of 1000 m, highlighting the controls of sinking particle over microbial connectivity from the epipelagic to mesopelagic zone. However, due to the biological migration and ocean mixing, the fecal-associated bacteria and protistan consumers unexpectedly emerge and the degradation index of DOM substantially alters around 1000-1200 m. Collectively, we unveil the significance of multi-faceted particle dispersion, which supports the connectivity and variability of deep ocean microbial communities.PMID:37805181 | DOI:10.1016/j.envres.2023.117310

J Nutr. 2023 Oct 5:S0022-3166(23)72624-2. doi: 10.1016/j.tjnut.2023.10.003. Online ahead of print.NO ABSTRACTPMID:37805045 | DOI:10.1016/j.tjnut.2023.10.003

J Ethnopharmacol. 2023 Oct 5:117248. doi: 10.1016/j.jep.2023.117248. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Herba Wanlenbergiae, named 'Lanhuashen' (LHS) in Chinese, is derived from the dried herba of Wahlenbergia marginata (Thunb.) A.DC. It is an abundant resource that has been used in traditional Chinese medicine (TCM) for over 600 years. LHS has the effects of enriching consumptive disease and relieving deficient heat, consistent with the therapy for type 2 diabetes mellitus (T2DM) in TCM. As the basic remedy of Yulan Jiangtang capsules, a listed Chinese medicine specifically for treating T2DM, LHS is a potential candidate for an anti-T2DM drug. However, due to the lack of pharmacodynamic studies and chemical component analysis, the application and development of LHS as a treatment for T2DM have been hindered.AIM OF THE STUDY: To evaluate the regulation of the disorder of glucolipid metabolism using LHS extracts and its therapeutic potential in T2DM.MATERIALS AND METHODS: Chemical components in LHS extracts were analysed using UPLC-Q Exactive-Orbitrap-MS. Subsequently, high sucrose diet (HSD)-induced Drosophila melanogaster were used as suitable models for T2DM in vivo. Behavioural and biochemical tests were performed to evaluate the regulation of the disorder of glucolipid metabolism using LHS in T2DM flies. Furthermore, integrative metabolomic and transcriptomic analysis was applied to reveal the specific effects of LHS extracts on metabolites and genes. Meanwhile, bioinformatic analysis was carried out to predict the targeted transcription factors (TFs) and potentially effective components of LHS extracts.RESULTS: We redefined the chemical profile of LHS with 76 identified chemical components, including 65 chemical components for the first time. As indicated by decreased trehalose, glucose and triglyceride levels and increased total protein levels, LHS extracts were perceived to alleviate the disorder of glucolipid metabolism in HSD-induced T2DM fruit flies. Integrative metabolomic and transcriptomic analysis revealed that LHS extracts eliminated the accumulation of sphingolipids and subsequently stimulated the positive cross-regulation mediated by the sphingosine 1-phosphate (S1P) axis, resulting in the activation of the phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) signalling pathway and inhibition of lysosome-mediated apoptosis. Bioinformatic analysis revealed that the upstream TFs, transcriptional enhancer factor TEF-5 (TEAD3) and peroxisome proliferator-activated receptor alpha (PPARA), were the potential targets of atractylenolide III, dihydrokaempferol and syringaldehyde, the potentially effective components of LHS extracts. Therefore, this TF network was plausibly the basis for the efficacy.CONCLUSIONS: LHS extracts broadly modulated TF-dependent gene expression and subsequently stimulated the positive cross-regulation mediated by the S1P axis to ameliorate the disorder of glucolipid metabolism. Our study provides critical evidence considering LHS as a potential drug candidate for T2DM, inspiring the discovery and development of innovative therapeutic agents based on the cross-regulation mediated by the S1P axis for treating T2DM and related complications.PMID:37804923 | DOI:10.1016/j.jep.2023.117248

Food Chem Toxicol. 2023 Oct 5:114087. doi: 10.1016/j.fct.2023.114087. Online ahead of print.ABSTRACTWampee (Clausena lansium) is a common fruit in South Asia. The pulp is a tasty food, and the seed is a typical traditional herb in China. However, we identified a primary toxic compound, Lansamide I, by NMR and X-ray diffraction of single-crystal. The compound occurred at 4.17 ± 0.16 mg/kg of dried seed and 0.08 ± 0.01 g/kg of fresh fruit. In our phenotype-based toxicity investigation, the compound caused decreased hatchability of zebrafish eggs, increased malformations such as enlarged yolk sacs and pericardial edema, and delayed body length development. Moreover, the compound also caused nerve cell damage and decreased locomotor activity. The compound caused an increase in peroxidation levels in vivo, with increases in both malondialdehyde and superoxide dismutase levels, but did not interfere with acetylcholinesterase levels. Metabolomic studies found that the compound caused significant up-regulation of 16 metabolites, mainly amino acids and peptides, which were involved in the nucleotide metabolism pathway and the betaine biosynthesis module. The qRT-PCR revealed that the substance interfered with the mRNA expression of tat and dctpp. These discoveries offer fresh perspectives on the toxicity mechanisms and metabolic response to the primary harmful moleculesin wampee, which could inform the rational usage of wampee resources.PMID:37804914 | DOI:10.1016/j.fct.2023.114087

Cell Metab. 2023 Sep 29:S1550-4131(23)00341-8. doi: 10.1016/j.cmet.2023.09.010. Online ahead of print.ABSTRACTThe intestinal epithelium has a high turnover rate and constantly renews itself through proliferation of intestinal crypt cells, which depends on insufficiently characterized signals from the microenvironment. Here, we showed that colonic macrophages were located directly adjacent to epithelial crypt cells in mice, where they metabolically supported epithelial cell proliferation in an mTORC1-dependent manner. Specifically, deletion of tuberous sclerosis complex 2 (Tsc2) in macrophages activated mTORC1 signaling that protected against colitis-induced intestinal damage and induced the synthesis of the polyamines spermidine and spermine. Epithelial cells ingested these polyamines and rewired their cellular metabolism to optimize proliferation and defense. Notably, spermine directly stimulated proliferation of colon epithelial cells and colon organoids. Genetic interference with polyamine production in macrophages altered global polyamine levels in the colon and modified epithelial cell proliferation. Our results suggest that macrophages act as "commensals" that provide metabolic support to promote efficient self-renewal of the colon epithelium.PMID:37804836 | DOI:10.1016/j.cmet.2023.09.010

Phytomedicine. 2023 Sep 23;121:155111. doi: 10.1016/j.phymed.2023.155111. Online ahead of print.ABSTRACTBACKGROUND: Current evidence indicates a rising global prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD), which is closely associated to conditions such as obesity, dyslipidemia, insulin resistance, and metabolic syndrome. The relationship between the gut microbiome and metabolites in NAFLD is gaining attention understanding the pathogenesis and progression of dysregulated lipid metabolism and inflammation. The Xie Zhuo Tiao Zhi (XZTZ) decoction has been employed in clinical practice for alleviating hyperlipidemia and symptoms related to metabolic disorders. However, the pharmacological mechanisms underlying the effects of XZTZ remain to be elucidated.PURPOSE: The objective of this study was to examine the pharmacological mechanisms underlying the hypolipidemic and anti-inflammatory effects of XZTZ decoction in a mouse model of NAFLD, as well as the effects of supplementing exogenous metabolites on PO induced cell damage and lipid accumulation in cultured hepatocytes.METHODS: A high-fat diet (HFD) mouse model was established to examine the effects of XZTZ through oral gavage. The general condition of mice and the protective effect of XZTZ on liver injury were evaluated using histological and biochemical methods. Hematoxylin and eosin staining (H&E) staining and oil red O staining were performed to assess inflammatory and lipid accumulation detection, and cytokine levels were quantitatively analyzed. Additionally, the study included full-length 16S rRNA sequencing, liver transcriptome analysis, and non-targeted metabolomics analysis to investigate the relationship among intestinal microbiome, liver metabolic function, and XZTZ decoction.RESULTS: XZTZ had a significant impact on the microbial community structure in NAFLD mice. Notably, the abundance of Ileibacterium valens, which was significantly enriched by XZTZ, exhibited a negative correlation with liver injury biomarkers such as, alanine transaminase (ALT) and aspartate transaminase (AST) activity. Moreover, treatment with XZTZ led to a significant enrichment of the purine metabolism pathway in liver tissue metabolites, with inosine, a purine metabolite, showing a significant positive correlation with the abundance of I. valens. XZTZ and inosine also significantly enhanced fatty acid β-oxidation, which led to a reduction in the expression of pro-inflammatory cytokines and the inhibition of liver pyroptosis. These effects contributed to the mitigation of liver injury and hepatocyte damage, both in vivo and vitro. Furthermore, the utilization of HPLC fingerprints and UPLC-Q-TOF-MS elucidated the principal constituents within the XZTZ decoction, including naringin, neohesperidin, atractylenolide III, 23-o-Acetylalisol B, pachymic acid, and ursolic acid which are likely responsible for its therapeutic efficacy. Further investigations are imperative to fully uncover and validate the pharmacodynamic mechanisms underlying these observations.CONCLUSION: The administration of XZTZ decoction demonstrates a protective effect on the livers of NAFLD mice by inhibiting lipid accumulation and reducing hepatocyte inflammatory damage. This protective effect is mediated by the upregulation of I.valens abundance in the intestine, highlighting the importance of the gut-liver axis. Furthermore, the presesnce of inosine, adenosine, and their derivatives are important in promoting the protective effects of XZTZ. Furthermore, the in vitro approaching, we provide hitherto undocumented evidence indicating that the inosine significantly improves lipid accumulation, inflammatory damage, and pyroptosis in AML12 cells incubated with free fatty acids.PMID:37804819 | DOI:10.1016/j.phymed.2023.155111

Food Chem. 2023 Sep 22;435:137548. doi: 10.1016/j.foodchem.2023.137548. Online ahead of print.ABSTRACTThis study investigated the impact of plasma-activated water (PAW) on Raphanus sativus (radish) roots at the level of proteins and metabolites. PAW treatment induced the accumulation of reactive oxygen species (ROS) and nitrogen oxide species (NOx) in radish and enhanced the activities of antioxidant enzymes. Proteomic analysis resulted in the identification of 6054 proteins, including 1845 PAW-modulated proteins that were majorly associated with energy metabolism, ROS-detoxification, phytohormones signaling, and biosynthesis of glucosinolates. Subsequent metabolomics analysis identified 314 metabolites, of which 194 showed significant differences in response to PAW treatment. In particular, PAW treatment triggered the accumulation of functional compounds such as vitamin C, vitamin B5, glutathione, and glucosinolates, the well-known characteristic compounds of the Brassicaceae family. Further, integrating proteomics and metabolomics data provided novel insights into the molecular mechanism governing plasma-induced growth and the accumulation of these functional compounds in radish plants.PMID:37804729 | DOI:10.1016/j.foodchem.2023.137548

Food Chem. 2023 Sep 28;435:137574. doi: 10.1016/j.foodchem.2023.137574. Online ahead of print.ABSTRACTIn this work, a comparative chemical-biological study of nine plum varieties (Prunus domestica L. and Prunus salicina Lindl.) with two commercial ones was carried out to improve their cultivation and use in the agri-food chain. The chemical quali-quantitative fingerprint by HR-Orbitrap/ESI-MS showed similar profiles, being 'Rossa Casa Velasco' the richest in phenols and anthocyanins. All the extracts were investigated for their in vitro antioxidant as well as antiangiogenic activity by two in vivo models, chick chorioallantoic membrane and zebrafish embryos. Among investigated varieties 'Scarrafona', 'Rusticano', 'Marisa', 'Rossa Casa Velasco', 'Verdone', and 'Sangue di Drago' showed the best antiangiogenic activities (30-50 % inhibition). Finally, the chemical/biological datasets processed with a bioinformatic approach revealed that a large group of flavonoids, procyanidins, and anthocyanins significantly correlated with all the three antioxidant tests (DPPH, FRAP, and ABTS), while quinic acid and icariside F2 resulted positively correlated with CAM at both 100 and 200 μg/egg.PMID:37804727 | DOI:10.1016/j.foodchem.2023.137574

Int Immunopharmacol. 2023 Oct 4;124(Pt B):111001. doi: 10.1016/j.intimp.2023.111001. Online ahead of print.ABSTRACTOBJECTIVE: Cachexia, marked by muscle atrophy, poses substantial challenges for prevention and treatment. This study delves into the unclear role of butyrate, a gut microbiota metabolite, in cachexia by examining gut microbiota and short-chain fatty acid (SCFA) profiles in human and mouse fecal samples.METHODS: We analyzed cachexia-associated gut microbiota and SCFA profiles using 16S rRNA sequencing and metabolomic techniques. Mouse cachexia models were developed with C26 cells, and LPS was used to induce muscle cell atrophy in C2C12 cells. We evaluated butyrate's in vivo effects on intestinal health, muscle preservation, inflammation, and macrophage activity. In vitro studies focused on butyrate's influence on macrophage polarization and the subsequent effects on muscle cells.RESULTS: Both cachexia patients and mice exhibited gut microbiota imbalances, irregular butyrate concentrations, and a decline in butyrate-producing bacteria. In vivo tests showed that butyrate counteract cachexia-induced muscle atrophy by adjusting the Akt/mTOR/Foxo3a and Fbox32/Trim63 pathways. These butyrate also bolstered intestinal barrier integrity, minimized endotoxin migration, and mitigated oxidative stress. Furthermore, butyrate curtailed inflammation and macrophage penetration in muscles. In vitro experimental results demonstrate that butyrate inhibit macrophage polarization towards the M1 phenotype and promote polarization towards the M2 phenotype. Both M1 and M2 macrophages influence the aforementioned pathways and oxidative stress, participating in the regulation of muscle cell atrophy.CONCLUSION: Our study delineates the intricate interplay between gut microbiota dysbiosis, butyrate fluctuations, and cachexia progression. Butyrate not only reinforces the intestinal barrier but also orchestrates macrophage polarization, mitigating muscle atrophy and averting cachexia-induced muscle deterioration. Concurrently, the M1 and M2 macrophages play pivotal roles in modulating skeletal muscle cell atrophy. This highlights the potential of utilizing the gut-derived metabolite butyrate as a promising therapeutic approach for addressing cachexia-related issues.PMID:37804658 | DOI:10.1016/j.intimp.2023.111001

J Pharm Biomed Anal. 2023 Sep 26;237:115750. doi: 10.1016/j.jpba.2023.115750. Online ahead of print.ABSTRACTIn the last decade, the kynurenine pathway, which is the primary metabolic route for tryptophan (TRP) catabolism, has sparked great interest in the pharmaceutical sciences due to its role in immune regulation and cancer immunoediting. In this context, the development of cell-based assays might represent a tool to: i) characterize the cell secretome according to cell types; ii) gain more insight into the role of kynurenines in different disease scenarios; iii) screen hIDO1 (human indoleamine 2,3-dioxygenase) inhibitors and evaluate their effect on downstream TRP-catabolizing enzymes. This paper reports a validated Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) method to simultaneously quantify TRP, L-kynurenine (KYN), xanthurenic acid (XA), 3-hydroxykynurenine (3OHKYN), kynurenic acid (KA), 3-hydroxyanthranilic acid (3OHAA), anthranilic acid (AA), 5-hydroxytryptamine (serotonin, 5HT) and tryptamine (TRYP) in Dulbecco's Modified Eagle and Eagle's Minimum Essential Media (DMEM and EMEM, respectively). The quantitative method was validated according to FDA, ICH and EMA guidelines, later applied: i) to assess the impact of selective inhibition of hIDO1 or hTDO (human tryptophan 2,3-dioxygenase) on the kynurenine pathway in A375 (melanoma), MDA-MB-231 (breast cancer), and U87 (glioblastoma) cell lines using multivariate analysis (MVA); ii) to determine the IC50 values of both well-known (i.e., epacadostat, linrodostat) and the novel hIDO1 inhibitor (i.e., BL5) in the aforementioned cell lines. The proposed LC-MS/MS method is reliable and robust. Furthermore, it is highly versatile and suitable for applications in the preclinical drug research and in vitro assays.PMID:37804639 | DOI:10.1016/j.jpba.2023.115750

Curr Opin Chem Biol. 2023 Oct 5;77:102400. doi: 10.1016/j.cbpa.2023.102400. Online ahead of print.ABSTRACTMetabolomics has rapidly been adopted as one of the key methods in nutrition research. This review focuses on the recent developments and updates in the field, including the analytical methodologies that encompass improved instrument sensitivity, sampling techniques and data integration (multiomics). Metabolomics has advanced the discovery and validation of dietary biomarkers and their implementation in health research. Metabolomics has come to play an important role in the understanding of the role of small molecules resulting from the diet-microbiota interactions when gut microbiota research has shifted towards improving the understanding of the activity and functionality of gut microbiota rather than composition alone. Currently, metabolomics plays an emerging role in precision nutrition and the recent developments therein are discussed.PMID:37804582 | DOI:10.1016/j.cbpa.2023.102400

Plant Physiol. 2023 Oct 7:kiad535. doi: 10.1093/plphys/kiad535. Online ahead of print.ABSTRACTDuring photosynthesis, plants must manage strong fluctuations in light availability on different time scales, leading to long-term acclimation and short-term responses. However, little is known about the regulation and coordination of these processes and the modulators involved. In this study, we used proteomics, metabolomics, and reverse genetics to investigate how different light environmental factors, such as intensity or variability, affect long-term and short-term acclimation responses of Arabidopsis (Arabidopsis thaliana) and the importance of the chloroplast redox network in their regulation. In the wild type, high light, but not fluctuating light, led to large quantitative changes in the proteome and metabolome, accompanied by increased photosynthetic dynamics and plant growth. This finding supports light intensity as a stronger driver for acclimation than variability. Deficiencies in NADPH-thioredoxin reductase C (NTRC) or thioredoxins m1/m2, but not thioredoxin f1, almost completely suppressed the reengineering of the proteome and metabolome, with both the induction of proteins involved in stress and redox responses and the repression of those involved in cytosolic and plastid protein synthesis and translation being strongly attenuated. Moreover, the correlations of protein or metabolite levels with light intensity were severely disturbed, suggesting a general defect in the light-dependent acclimation response, resulting in impaired photosynthetic dynamics. These results indicate a previously unknown role of NTRC and thioredoxins m1/m2 in modulating light acclimation at proteome and metabolome levels to control dynamic light responses. NTRC, but not thioredoxins m1/m2 or f1, also improves short-term photosynthetic responses by balancing the Calvin-Benson cycle in fluctuating light.PMID:37804523 | DOI:10.1093/plphys/kiad535

Expert Rev Proteomics. 2023 Oct 7. doi: 10.1080/14789450.2023.2268836. Online ahead of print.NO ABSTRACTPMID:37804136 | DOI:10.1080/14789450.2023.2268836

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2023 Sep;35(9):980-983. doi: 10.3760/cma.j.cn121430-20230607-00427.ABSTRACTOBJECTIVE: To investigate the effect of hyperoxia on intestinal metabolomics in mice.METHODS: Sixteen 8-week-old male C57BL/6 mice were randomly divided into hyperoxia group and control group, with 8 mice in each group. The hyperoxia group was exposed to 80% oxygen for 14 days. Mice were anesthetized and euthanized, and cecal contents were collected for untargeted metabolomics analysis by liquid chromatography-mass spectrometry (LC-MS) combined detection. Orthogonal partial least square discriminant analysis (OPLS-DA), volcano plot analysis, heat map analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the effects of hyperoxia on metabolism.RESULTS: (1) OPLS-DA analysis showed that R2Y was 0.967 and Q2 was 0.796, indicating that the model was reliable. (2) Volcano plot and heat map analysis showed significant statistical differences in the expression levels of metabolites between the two groups, with 541 up-regulated metabolites, 64 down-regulated metabolites, and 907 no differences, while the elevated 5-hydroxy-L-lysine was the most significant differential metabolite induced by high oxygen. (3) KEGG pathway enrichment analysis showed that porphyrin and chlorophyll metabolism (P = 0.005), lysine degradation (P = 0.047), and aromatic compound degradation (P = 0.024) were the targets affected by hyperoxia. (4) Differential analysis of metabolic products through KEGG enrichment pathway showed that hyperoxia had a significant impact on the metabolism of porphyrin and chlorophyll, lysine, and aromatic compounds such as benzene and o-cresol.CONCLUSIONS: Hyperoxia significantly induces intestinal metabolic disorders. Hyperoxia enhances the metabolism of porphyrins and chlorophyll, inhibits the degradation of lysine, and delays the degradation of aromatic compounds such as benzene and o-cresol.PMID:37803959 | DOI:10.3760/cma.j.cn121430-20230607-00427