PubMed

Nutr Metab Cardiovasc Dis. 2023 May 11:S0939-4753(23)00188-6. doi: 10.1016/j.numecd.2023.05.006. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Aortic dissection (AD), a severe clinical emergency with high mortality, is easily misdiagnosed as are other cardiovascular diseases. This study aimed at discovering plasma metabolic markers with the potential to diagnose AD and clarifying the metabolic differences between two subtypes of AD.METHODS AND RESULTS: To facilitate the diagnosis of AD, we investigated the plasma metabolic profile by metabolomic approach. A total 482 human subjects were enrolled in the study: 80 patients with AD (50 with Stanford type A and 30 with Stanford type B), 198 coronary artery disease (CAD) patients, and 204 healthy individuals. Plasma samples were submitted to targeted metabolomic analysis. The partial least-squares discriminant analysis models were constructed to illustrate clear discrimination of AD patients with CAD patients and healthy control. Subsequently, the metabolites that were clinically relevant to the disturbances in AD were identified. Twenty metabolites induced the separation of AD patients and healthy control, 9 of which caused the separation of CAD patients and healthy control. There are 11 metabolites specifically down-regulated in AD group. Subgroup analysis showed that the levels of glycerol and uridine were dramatically lower in the plasma of patients with Stanford type A AD than those in the healthy control or Stanford type B AD groups.CONCLUSION: This study characterized metabolomic profiles specifically associated with the pathogenesis and development of AD. The findings of this research may potentially lead to earlier diagnosis and treatment of AD.PMID:37263915 | DOI:10.1016/j.numecd.2023.05.006

J Appl Microbiol. 2023 Jun 1:lxad112. doi: 10.1093/jambio/lxad112. Online ahead of print.ABSTRACTAIM: The aim of the current study is to elucidate the inactivation and molecular response pattern of sublethal Listeria monocytogenes to cold plasma mediated two-pronged oxidative microenvironments from a high-throughput multi-omics perspective.METHODS AND RESULTS: First joint transcriptomics and metabolomics analyses revealed that significantly expressed genes and metabolites were mainly involved in enhanced transmembrane transport and Fe2+/Cu+ efflux, amino acids limitation, cytoplasmic pH homeostasis, reconfiguration of central carbon metabolism flux and energy conservation strategy, which triggered the surge of intracellular endogenous oxidative stress and finally mediated bacterial ferroptosis and pathogenicity attenuation. Typical antioxidant systems such as the TrxR-Trx system and common antioxidant genes (e.g. sodA, katA, ahpC, trxA, spxA) were inhibited, and the more prominent antioxidant pathways include methionine metabolism, pentose phosphate pathway and glutathione metabolism as well as the DNA repair systems.CONCLUSIONS: Therefore, our work confirmed from the transcriptional and metabolic as well as physiological levels that cold plasma-mediated intracellular oxidative stress induced big perturbations in pathways as a driving force for the inactivation and pathogenicity attenuation of L. monocytogenes.PMID:37263797 | DOI:10.1093/jambio/lxad112

J Chromatogr A. 2023 May 26;1703:464111. doi: 10.1016/j.chroma.2023.464111. Online ahead of print.ABSTRACTBranched chain fatty acids (BCFAs) are one of the important sub categories of fatty acids (FAs) which have unique functions in nature. They are commonly analyzed by GC-MS after derivatization to methyl esters (FAMEs). On the other hand, there is a lack of isomer-selective LC-MS methods which allow the distinction of different isomers with wide coverage of carbon chain length. In this work, a systematic retention and isomer selectivity study on seven commercially available UHPLC columns (six polysaccharide columns Chiralpak IA-U, IB-U, IC-U, ID-U, IG-U and IH-U; one Acquity UPLC CSH C18 column) was performed. Various experimental factors were evaluated including column temperatures, gradient profiles and flow rates to elucidate their effects on the separation ability of homologous series of BCFAs with distinct chain lengths, different branching types and branching positions. In general, IG-U outperformed the other columns in terms of isomer selectivity especially for the short and medium-chain BCFA isomers while RP C18 showed good potential in terms of selectivity for long-chain BCFA isomers. Furthermore, after the evaluation of the chromatographic retention pattern on the various columns and method optimization, we report a methodology for untargeted isomer-selective BCFA profiling without precolumn derivatization with UHPLC-ESI-MS/MS by quadrupole-time-of-flight instrument with SWATH acquisition. The best method provides selectivity for constitutional isomers of BCFAs covering distinct chain length (C5-C20) with different branching types (methyl or ethyl) and branching positions (2Me, 3Me, 4Me, 6Me, anteiso and iso-BCFAs) with an optimized LC condition on Acquity UPLC CSH C18 column. Finally, the optimized method was applied for the BCFAs profiling in lipid extracts of Staphylococcus aureus samples. Besides, pooled human platelets and pooled human plasma were evaluated as mammalian samples for presence of BCFAs as well. The new method showed strong potential for BCFA profiling in bacterial samples including different isomers anteiso and iso-BCFAs, which could be a useful tool for related subdisciplines in metabolomics and lipidomics in particular in combination with electron-activated dissociation MS. Compared to GC, the presented isomer selective LC methods can be also of great utility for preparative purposes. Equivalent (carbon) chain length numbers were calculated for RP18 and Chiralpak IG-U and compared to those of FAMEs obtained by GC.PMID:37262934 | DOI:10.1016/j.chroma.2023.464111

J Chromatogr A. 2023 May 26;1703:464110. doi: 10.1016/j.chroma.2023.464110. Online ahead of print.ABSTRACTCarbonyl compounds are among the most important flavor substances that affect the taste of Baijiu. However, high coverage analysis of carbonyl compounds is obstructed due to the poor ionization efficiency of these compounds. Here we report a chlorine isotope labeling-assisted ultrahigh-performance liquid chromatography-high resolution mass spectrometry-based method (CIL-UHPLCHRMS) for profiling and annotation of carbonyl compounds in sauce flavored-Baijiu Daqu. 4-Chloro-2-hydrazinylpyridine was demonstrated to be a good labeling reagent that could achieve highly sensitive profiling and high-coverage screening of carbonyl compounds in the absence of heavy isotope labeling reagents. In the analysis of eight carbonyl standards representing different carbonyl categories, l-(-)-fucose, 2-carboxybenzaldehyde, 2-hydroxyacetophenone and heptan-2-one could be ionized only after labeling and MS signals were significantly increased for other 4 standards with an enhancement factor ranging from 181-fold for 3-methoxysalicylaldehyde to 3141-fold for tridecan-2-one. The annotation was achieved based on multidimensional information including MS1, predicted tR, in silico MS/MS and manually annotated fragments. In total, 487 carbonyl compounds were detected in Baijiu Daqu, among which, 314 (64.5%) of them were positively or putatively identified. The outcome of the linearity (with a linear range of 2, 3 orders of magnitude), precision (less than 10%), and limit of detection (varied from 0.07 to 0.10 nM) indicated that the method was adequate for profiling carbonyl compounds in complex biological samples. The established method was successfully applied to study carbonyl compounds in Baijiu Daqu with different colors and different seasons. Taken collectively, the present work provides an effective, simple and economic strategy for comprehensive analysis of carbonyl compounds in complex matrix samples.PMID:37262933 | DOI:10.1016/j.chroma.2023.464110

Anal Chem. 2023 Jun 1. doi: 10.1021/acs.analchem.3c01078. Online ahead of print.ABSTRACTInfrared ion spectroscopy (IRIS) continues to see increasing use as an analytical tool for small-molecule identification in conjunction with mass spectrometry (MS). The IR spectrum of an m/z selected population of ions constitutes a unique fingerprint that is specific to the molecular structure. However, direct translation of an IR spectrum to a molecular structure remains challenging, as reference libraries of IR spectra of molecular ions largely do not exist. Quantum-chemically computed spectra can reliably be used as reference, but the challenge of selecting the candidate structures remains. Here, we introduce an in silico library of vibrational spectra of common MS adducts of over 4500 compounds found in the human metabolome database. In total, the library currently contains more than 75,000 spectra computed at the DFT level that can be queried with an experimental IR spectrum. Moreover, we introduce a database of 189 experimental IRIS spectra, which is employed to validate the automated spectral matching routines. This demonstrates that 75% of the metabolites in the experimental data set are correctly identified, based solely on their exact m/z and IRIS spectrum. Additionally, we demonstrate an approach for specifically identifying substructures by performing a search without m/z constraints to find structural analogues. Such an unsupervised search paves the way toward the de novo identification of unknowns that are absent in spectral libraries. We apply the in silico spectral library to identify an unknown in a plasma sample as 3-hydroxyhexanoic acid, highlighting the potential of the method.PMID:37262385 | DOI:10.1021/acs.analchem.3c01078

J Agric Food Chem. 2023 Jun 1. doi: 10.1021/acs.jafc.3c01383. Online ahead of print.ABSTRACTSoil salinity is a major conlinet limiting sustainable agricultural development in peach tree industry. In this study, lipid metabolomic pathway analysis indicated that phosphatidic acid is essential for root resistance to salt stress in peach seedlings. Through functional annotation analysis of differentially expressed genes in transcriptomics, we found that MAPK signaling pathway is closely related to peach tree resistance to salt stress, wherein PpMPK6 expression is significantly upregulated. Under salt conditions, the OE-PpMPK6 Arabidopsis thaliana (L.) Heynh. line showed higher resistance to salt stress than WT and KO-AtMPK6 lines. Furthermore, we found that the Na+ content in OE-PpMPK6 roots was significantly lower than that in WT and KO-AtMPK6 roots, indicating that phosphatidic acid combined with PpMPK6 activated the SOS1 (salt-overly-sensitive 1) protein to enhance Na+ efflux, thus alleviating the damage caused by NaCl in roots; these findings provide insight into the salt stress-associated transcriptional regulation.PMID:37262364 | DOI:10.1021/acs.jafc.3c01383

Cancer Discov. 2023 Jun 1:CD-22-0976. doi: 10.1158/2159-8290.CD-22-0976. Online ahead of print.ABSTRACTOncocytic (Hurthle cell) carcinoma of the thyroid (HCC) is genetically characterized by complex I mitochondrial DNA mutations and widespread chromosomal losses. Here, we utilize RNA-seq and metabolomics to identify candidate molecular effectors activated by these genetic drivers. We find glutathione biosynthesis, amino acid metabolism, mitochondrial unfolded protein response, and lipid peroxide scavenging to be increased in HCC. A CRISPR-Cas9 knockout screen in a new HCC model reveals which pathways are key for fitness, and highlights loss of GPX4, a defense against lipid peroxides and ferroptosis, as a strong liability. Rescuing complex I redox activity with the yeast NADH dehydrogenase (NDI1) in HCC cells diminishes ferroptosis sensitivity, while inhibiting complex I in normal thyroid cells augments ferroptosis induction. Our work demonstrates unmitigated lipid peroxide stress to be an HCC vulnerability that is mechanistically coupled to the genetic loss of mitochondrial complex I activity.PMID:37262067 | DOI:10.1158/2159-8290.CD-22-0976

Adv Mater. 2023 Jun 1:e2303432. doi: 10.1002/adma.202303432. Online ahead of print.ABSTRACTBacterial biofilm-associated infections (BAIs) are the leading cause of prosthetic implant failure. The dense biofilm structure prevents antibiotic penetration, while the highly acidic and H2 O2 -rich biofilm microenvironment (BME) dampens the immunological response of antimicrobial macrophages. Conventional treatments that fail to consistently suppress escaping planktonic bacteria from biofilm result in refractory recolonization, allowing BAIs to persist. Herein, we propose a BME-responsive copper-doped polyoxometalate clusters (Cu-POM) combination with mild photothermal therapy (PTT) and macrophage immune re-rousing for BAI eradication at all stages. The self-assembly of Cu-POM in BME converted endogenous H2 O2 to toxic ·OH through chemodynamic therapy (CDT) and generated a mild PTT effect to induce bacterial metabolic exuberance, resulting in loosening the membrane structure of the bacteria, enhancing copper transporter activity and increasing intracellular Cu-POM flux. Metabolomics revealed that intracellular Cu-POM overload restricted the TCA cycle and peroxide accumulation, promoting bacterial cuproptosis-like death. CDT re-rousing macrophages scavenge planktonic bacteria escaping biofilm disintegration through enhanced chemotaxis and phagocytosis. Overall, BME-responsive Cu-POM promoted bacterial cuproptosis-like death via metabolic interference, while also re-rousing macrophage immune response for further planktonic bacteria elimination, resulting in all-stage BAI clearance and providing a new reference for future clinical application. This article is protected by copyright. All rights reserved.PMID:37262064 | DOI:10.1002/adma.202303432

Stem Cells Dev. 2023 Jun 1. doi: 10.1089/scd.2023.0079. Online ahead of print.ABSTRACTMesenchymal stem cells (MSCs) are essential players in multiple physiological processes in vivo and is a promising cell-based therapy for various diseases. Nonetheless, MSCs suffer from senescence with expansion culture, leading to a limitation for their clinical application. Recently, it was reported that small extracellular vesicles (sEV) are involved in the regulation of senescence in tumor cells and fibroblasts. However, the biological roles of sEV in senescent MSCs (Sen MSCs) are poorly understood. Here, we established a replicative senescence model of MSCs by successive passages and compared the phenotypic changes between pre-senescent MSCs (Pre-Sen MSCs) and Sen MSCs, and found that Sen MSCs exhibited a diminished adipogenic and osteogenic differentiation potential, and elevated senescence-associated secretory phenotype (SASP) levels. In addition, we found that sEV secretion was increased in Sen MSCs, and inhibition of sEV secretion led to apoptosis, DNA damage and decreased cell viability, suggesting that increased sEV secretion plays an important role in maintaining Sen MSCs homeostasis. To further investigate the molecular mechanisms, metabolomics profiling of Pre-Sen MSCs-derived sEV (Pre-Sen-sEV) and Sen MSCs-derived sEV (Sen-sEV) was performed. The results showed that lipid metabolites were significantly increased in Sen-sEV, and these significantly up-regulated lipid metabolites were shown to be toxic for inducing cellular senescence and apoptosis in previous studies. KEGG analysis revealed that differential metabolites between Pre-Sen-sEV and Sen-sEV were mainly enriched in 25 signaling pathways, of which 21 metabolic pathways have been shown to be closely associated with senescence. Taken together, our findings suggested that increased sEV secretion maintains Sen MSCs homeostasis at least in part by excreting harmful lipids, thus providing new insights into the regulation of senescence by sEV.PMID:37262010 | DOI:10.1089/scd.2023.0079

Rejuvenation Res. 2023 Jun 1. doi: 10.1089/rej.2023.0009. Online ahead of print.ABSTRACTBACKGROUND: Cerebral ischemia-reperfusion (CIR) injury occurs as a secondary injury during the treatment of ischemic stroke (IS). There is a high death rate and morbidity due to IS throughout the world. Even though Naoxintong Capsule (NXT) is effective in the treatment of CIR, its mechanisms of action are unclear.PURPOSE: The study aims to explore the clear mechanism associated with NXT therapy for CIR.METHODS: We established the model of middle cerebral artery occlusion (MCAO) to evaluate the neurological function and assess the infarct size. Brain tissue metabolomics was used to identify different metabolites, and metabolic profiling systems enriched metabolic pathways. Then, the potential targets of NXT in the treatment of CIR were explored by proteomic, transcriptomic and metabolomic methods.RESULTS: NXT improves CIR Symptoms. We found potential 11 proteins and corresponding metabolites involved in NXT treatment of CIR. Most of these metabolites are regulated to restore after treatment. According to network pharmacology, we found 6 hub genes including Glb1, Gmps, Pfas, Atic, Gaa and Acox1, and their associated core metabolites and pathways.PMID:37261991 | DOI:10.1089/rej.2023.0009

FASEB J. 2023 Jul;37(7):e23014. doi: 10.1096/fj.202300261RR.ABSTRACTParenteral nutrition, received by many patients with intestinal failure, can induce hepatobiliary complications, which is termed as parenteral nutrition-associated liver disease (PNALD). The spectrum of PNALD ranges from cholestasis and steatosis to fibrosis and cirrhosis. Although many factors contribute to the pathogenesis of PNALD, the underlying mechanisms remain unclear. In this study, we performed targeted metabolomics to characterize the metabolomic profile in neonatal piglets receiving total parenteral nutrition (TPN) or enteral nutrition (EN) for 1 or 2 weeks. Overall, the metabolomic signature of TPN groups differed from EN groups at both time points. Among the 20 acylcarnitines identified, a majority of them were significantly reduced in TPN groups. KEGG pathway analysis showed that phenylalanine metabolism-associated pathways were dysregulated accompanied by more progressive liver steatosis associated with TPN. Next, we evaluated phenylalanine catabolism and its association with fatty acid oxidation in piglets and rats with PNALD. We showed that the hepatic expression of phenylalanine-degrading enzyme phenylalanine hydroxylase (PAH) was reduced and systemic phenylalanine levels were increased in both animal models of PNALD. Moreover, carnitine palmitoyltransferase 1A, a central regulator of fatty acid oxidation, was downregulated and its expression was negatively correlated with phenylalanine levels in TPN-fed animals. To explore the effects of phenylalanine accumulation on lipid metabolism, we treated HepG2 cells with phenylalanine co-cultured with sodium palmitate or soybean oil emulsion to induce lipid accumulation. We found that phenylalanine treatment exacerbated lipid accumulation by inhibiting fatty acid oxidation without affecting fatty acid synthesis. In summary, our findings establish a pathogenic role of increased phenylalanine levels in driving liver steatosis, linking dysregulation of phenylalanine catabolism with lipid accumulation in the context of PNALD.PMID:37261736 | DOI:10.1096/fj.202300261RR

Int Microbiol. 2023 Jun 1. doi: 10.1007/s10123-023-00375-9. Online ahead of print.ABSTRACTThe compound known as effective microorganisms (EMs) is widely used in aquaculture to improve water quality, but how they affect the health of Chinese mitten crab (Eriocheir sinensis) is unclear, especially in terms of intestinal microbiota and serum metabolites. In this study, we fed juvenile crabs with an EM-containing diet to explore the effects of EM on the physiological status, intestinal microbiome, and metabolites of E. sinensis. The activities of alanine aminotransferase and alkaline phosphatase were significantly enhanced by EM, indicating that EM supplementation effectively enhanced the antioxidant capacity of E. sinensis. Proteobacteria, Tenericutes, Firmicutes, Bacteroidetes, and Actinobacteria were the main intestinal microbes in both the control and EM groups. Linear discriminant effect size analysis showed that Fusobacteriaceae, Desulfovibrio, and Morganella were biomarkers in the control group, and Exiguobacterium and Rhodobacteraceae were biomarkers in the EM group. Metabolomics analysis revealed that EM supplementation increased cellular energy sources and decreased protein consumption, and oxidative stress. Together, these results indicate that EM can optimize the intestinal microbiome and serum metabolites, thereby benefiting the health of E. sinensis.PMID:37261580 | DOI:10.1007/s10123-023-00375-9

Elife. 2023 Jun 1;12:e84508. doi: 10.7554/eLife.84508. Online ahead of print.ABSTRACTCD73 is an ectonucleotidase overexpressed on tumor cells that suppresses anti-tumor immunity. Accordingly, several CD73 inhibitors are currently being evaluated in the clinic, including in large randomized clinical trials. Yet, the tumor cell-intrinsic impact of CD73 remain largely uncharacterized. Using metabolomics, we discovered that CD73 significantly enhances tumor cell mitochondrial respiration and aspartate biosynthesis. Importantly, rescuing aspartate biosynthesis was sufficient to restore proliferation of CD73-deficient tumors in immune deficient mice. Seahorse analysis of a large panel of mouse and human tumor cells demonstrated that CD73 enhanced oxidative phosphorylation (OXPHOS) and glycolytic reserve. Targeting CD73 decreased tumor cell metabolic fitness, increased genomic instability and suppressed poly ADP ribose polymerase (PARP) activity. Our study thus uncovered an important immune-independent function for CD73 in promoting tumor cell metabolism, and provides the rationale for previously unforeseen combination therapies incorporating CD73 inhibition.PMID:37261423 | DOI:10.7554/eLife.84508

Front Oncol. 2023 May 16;13:1125855. doi: 10.3389/fonc.2023.1125855. eCollection 2023.ABSTRACTBACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a poor patient prognosis. Remarkably, PDAC is one of the most aggressive and deadly tumor types and is notorious for its resistance to all types of treatment. PDAC resistance is frequently associated with a wide metabolic rewiring and in particular of the glycolytic branch named Hexosamine Biosynthetic Pathway (HBP).METHODS: Transcriptional and bioinformatics analysis were performed to obtain information about the effect of the HBP inhibition in two cell models of PDAC. Cell count, western blot, HPLC and metabolomics analyses were used to determine the impact of the combined treatment between an HBP's Phosphoglucomutase 3 (PGM3) enzyme inhibitor, named FR054, and erastin (ERA), a recognized ferroptosis inducer, on PDAC cell growth and survival.RESULTS: Here we show that the combined treatment applied to different PDAC cell lines induces a significant decrease in cell proliferation and a concurrent enhancement of cell death. Furthermore, we show that this combined treatment induces Unfolded Protein Response (UPR), NFE2 Like BZIP Transcription Factor 2 (NRF2) activation, a change in cellular redox state, a greater sensitivity to oxidative stress, a major dependence on glutamine metabolism, and finally ferroptosis cell death.CONCLUSION: Our study discloses that HBP inhibition enhances, via UPR activation, the ERA effect and therefore might be a novel anticancer mechanism to be exploited as PDAC therapy.PMID:37260977 | PMC:PMC10227458 | DOI:10.3389/fonc.2023.1125855

Front Plant Sci. 2023 May 16;14:1166933. doi: 10.3389/fpls.2023.1166933. eCollection 2023.ABSTRACTProgression of leaf senescence consists of both degenerative and nutrient recycling processes in crops including wheat. However, the levels of metabolites in flag leaves in spring-cultivated wheat, as well as biosynthetic pathways involved under different nitrogen fertilization regimes, are largely unknown. Therefore, the present study employed a widely untargeted metabolomic profiling strategy to identify metabolites and biosynthetic pathways that could be used in a wheat improvement program aimed at manipulating the rate and onset of senescence by handling spring wheat (Dingxi 38) flag leaves sampled from no-, low-, and high-nitrogen (N) conditions (designated Groups 1, 2, and 3, respectively) across three sampling times: anthesis, grain filling, and end grain filling stages. Through ultrahigh-performance liquid chromatography-tandem mass spectrometry, a total of 826 metabolites comprising 107 flavonoids, 51 phenol lipids, 37 fatty acyls, 37 organooxygen compounds, 31 steroids and steroid derivatives, 18 phenols, and several unknown compounds were detected. Upon the application of the stringent screening criteria for differentially accumulated metabolites (DAMs), 28 and 23 metabolites were differentially accumulated in Group 1_vs_Group 2 and Group 1_vs_Group 3, respectively. From these, 1-O-Caffeoylglucose, Rhoifolin, Eurycomalactone;Ingenol, 4-Methoxyphenyl beta-D-glucopyranoside, and Baldrinal were detected as core conserved DAMs among the three groups with all accumulated higher in Group 1 than in the other two groups. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that tropane, piperidine, and pyridine alkaloid biosynthesis; acarbose and validamycin biosynthesis; lysine degradation; and biosynthesis of alkaloids derived from ornithine, lysine, and nicotinic acid pathways were the most significantly (p < 0.05) enriched in Group 1_vs_Group 2, while flavone and flavonol as well as anthocyanins biosynthetic pathways were the most significantly (p < 0.05) enriched in Group 1_vs_Group 3. The results from this study provide a foundation for the manipulation of the onset and rate of leaf senescence and N remobilization in wheat.PMID:37260937 | PMC:PMC10227437 | DOI:10.3389/fpls.2023.1166933

Front Bioeng Biotechnol. 2023 May 16;11:1193095. doi: 10.3389/fbioe.2023.1193095. eCollection 2023.ABSTRACTFermentation is extremely important for the formation of the special flavor of Wuyi rock tea. This study determined volatile metabolite contents using GC-MS technique and futher analyzed their odor characteristics during the traditional deep fermentation technology of Wuyi rock tea. The results showed that 17 characteristic compounds significantly changed during the first stage of the preliminary processing, namely fresh leaves, withering and fermentation. The key to the formation of floral aroma lied in dihydromyrcenol, and the woody aroma derived from six terpenoids, and their synthesis depended on dihydromyrcenol content. The fruity aroma was dominated by six esters, and the fruity aroma mainly came from (Z) -3-hexen-1-yl butyrate, (E) -3-hexen-1-yl butyrate and 5-Hexenyl butyrate. This study provided an important theoretical and practical basis for improving the preliminary processing of Wuyi rock tea.PMID:37260830 | PMC:PMC10228688 | DOI:10.3389/fbioe.2023.1193095

iScience. 2023 May 13;26(6):106881. doi: 10.1016/j.isci.2023.106881. eCollection 2023 Jun 16.ABSTRACTMass spectrometry (MS)-based untargeted metabolomic and lipidomic approaches are being used increasingly in biomedical research. The adoption and integration of these data are critical to the overall multi-omic toolkit. Recently, a sample extraction method called Multi-ABLE has been developed, which enables concurrent generation of proteomic and untargeted metabolomic and lipidomic data from a small amount of tissue. The proteomics field has a well-established set of software for processing of acquired data; however, there is a lack of a unified, off-the-shelf, ready-to-use bioinformatics pipeline that can take advantage of and prepare concurrently generated metabolomic and lipidomic data for joint downstream analyses. Here we present an R pipeline called MultiABLER as a unified and simple upstream processing and analysis pipeline for both metabolomics and lipidomics datasets acquired using liquid chromatography-tandem mass spectrometry. The code is available via an open-source license at https://github.com/holab-hku/MultiABLER.PMID:37260745 | PMC:PMC10227420 | DOI:10.1016/j.isci.2023.106881

Front Cell Infect Microbiol. 2023 May 16;13:1170748. doi: 10.3389/fcimb.2023.1170748. eCollection 2023.ABSTRACTGlobally, liver cancer poses a serious threat to human health and quality of life. Despite numerous studies on the microbial composition of the gut in hepatocellular carcinoma (HCC), little is known about the interactions of the gut microbiota and metabolites and their role in HCC. This study examined the composition of the gut microbiota and serum metabolic profiles in 68 patients with HCC, 33 patients with liver cirrhosis (LC), and 34 healthy individuals (NC) using a combination of metagenome sequencing and liquid chromatography-mass spectrometry (LC-MS). The composition of the serum metabolites and the structure of the intestinal microbiota were found to be significantly altered in HCC patients compared to non-HCC patients. LEfSe and metabolic pathway enrichment analysis were used to identify two key species (Odoribacter splanchnicus and Ruminococcus bicirculans) and five key metabolites (ouabain, taurochenodeoxycholic acid, glycochenodeoxycholate, theophylline, and xanthine) associated with HCC, which then were combined to create panels for HCC diagnosis. The study discovered that the diagnostic performance of the metabolome was superior to that of the microbiome, and a panel comprised of key species and key metabolites outperformed alpha-fetoprotein (AFP) in terms of diagnostic value. Spearman's rank correlation test was used to determine the relationship between the intestinal flora and serum metabolites and their impact on hepatocarcinogenesis and progression. A random forest model was used to assess the diagnostic performance of the different histologies alone and in combination. In summary, this study describes the characteristics of HCC patients' intestinal flora and serum metabolism, demonstrates that HCC is caused by the interaction of intestinal flora and serum metabolites, and suggests that two key species and five key metabolites may be potential markers for the diagnosis of HCC.PMID:37260707 | PMC:PMC10227431 | DOI:10.3389/fcimb.2023.1170748

Front Microbiol. 2023 May 16;14:1182563. doi: 10.3389/fmicb.2023.1182563. eCollection 2023.ABSTRACTRhizobium leguminosarum bv. viciae (Rlv) UPM791 effectively nodulates pea and lentil, but bacteroids contain a number of proteins differentially expressed depending on the host. One of these host-dependent proteins (C189) is similar to a diaminobutyrate-2-oxoglutarate aminotransferase (DABA-AT). DABA-AT activity was demonstrated with cell extracts and with purified protein, so C189 was renamed as Dat. The dat gene was strongly induced in the central, active area of pea nodules, but not in lentil. Mutants defective in dat were impaired in symbiotic performance with pea plants, exhibiting reduced shoot dry weight, smaller nodules, and a lower competitiveness for nodulation. In contrast, there were no significant differences between mutant and wild-type in symbiosis with lentil plants. A comparative metabolomic approach using cell-free extracts from bacteroids induced in pea and lentil showed significant differences among the strains in pea bacteroids whereas no significant differences were found in lentil. Targeted metabolomic analysis revealed that the dat mutation abolished the presence of 2,4-diaminobutyrate (DABA) in pea nodules, indicating that DABA-AT reaction is oriented toward the production of DABA from L-aspartate semialdehyde. This analysis also showed the presence of L-homoserine, a likely source of aspartate semialdehyde, in pea bacteroids but not in those induced in lentil. The dat mutant showed impaired growth when cells were grown with L-homoserine as nitrogen source. Inclusion of DABA or L-homoserine as N source suppressed pantothenate auxotropy in Rlv UPM791, suggesting DABA as source of the pantothenate precursor β-alanine. These data indicate that Rlv UPM791 Dat enzyme is part of an adaptation mechanism of this bacterium to a homoserine-rich environment such as pea nodule and rhizosphere.PMID:37260681 | PMC:PMC10228743 | DOI:10.3389/fmicb.2023.1182563

Evid Based Complement Alternat Med. 2023 May 23;2023:2442505. doi: 10.1155/2023/2442505. eCollection 2023.ABSTRACTBACKGROUND: With the continuous advancement of clinical application and experimental research of JTP, the application prospect of JTP in nervous system diseases and metabolic diseases is becoming increasingly clear. Jiaotai Pill (JTP) is a traditional Chinese medicine formula for insomnia, consisting of Coptidis rhizoma and Cinnamomi cortex, which dates back to Han Shi Yi Tong in the Ming Dynasty of China.OBJECTIVE: Based on the brain-gut axis theory, this paper aims to explore the potential mechanism of JTP in the intervention of insomnia by using intestinal microbiome and metabolomics technology, taking the animal model of insomnia as the research object, so as to provide experimental basis for its further application and research.METHODS: The insomnia mouse model was induced by intraperitoneal injection of para-chlorophenylalanine (PCPA). The clinical equivalent dose of JTP was administered by gavage for one week. The efficacy of JTP was evaluated by behavioral tests, serum biochemical detection, and brain histomorphological observation. The contents of cecum were analyzed by microbiomics and metabolomics.RESULTS: The results show that insomnia caused by PCPA led to daytime dysfunction, higher HPA axis hormone levels, and morphologically impaired hippocampus. JTP reversed these anomalies. Omics research indicates that JTP significantly reduced gut α diversity; at the phylum level, JTP reduced the relative abundance of Firmicutes, Deferribacterota, Cyanobacteria, and Actinobacteriota and increased the relative abundance of Verrucomicrobiota, Proteobacteria, and Desulfobacterota. At the genus level, JTP reduced the relative abundance of Muribaculaceae, Lachnospiraceae_NK4A136_group, Alistipes, Colidextribacter, Muribaculum, and Mucispirillum and increased the relative abundance of Bacteroides and Akkermansia. JTP also reversed the activation of the linoleic acid metabolism pathway induced by insomnia. The combined analysis of omics suggests that JTP may play a role by regulating the inflammatory state of the body. Further gene expression analysis of brain tissue confirmed this.CONCLUSIONS: We hypothesize that JTP may achieve insomnia relief by eliminating inflammation-causing bacteria in the gut and reducing inflammation levels through the brain-gut axis, pointing to potential targets and pathways for future research on JTP.PMID:37260523 | PMC:PMC10229250 | DOI:10.1155/2023/2442505