PubMed

BMC Genomics. 2023 Sep 19;24(1):554. doi: 10.1186/s12864-023-09656-z.ABSTRACTBACKGROUND: The Inonotus obliquus mushroom, a wondrous fungus boasting edible and medicinal qualities, has been widely used as a folk medicine and shown to have many potential pharmacological secondary metabolites. The purpose of this study was to supply a global landscape of genome-based integrated omic analysis of the fungus under lab-growth conditions.RESULTS: This study presented a genome with high accuracy and completeness using the Pacbio Sequel II third-generation sequencing method. The de novo assembled fungal genome was 36.13 Mb, and contained 8352 predicted protein-coding genes, of which 365 carbohydrate-active enzyme (CAZyme)-coding genes and 19 biosynthetic gene clusters (BCGs) for secondary metabolites were identified. Comparative transcriptomic and proteomic analysis revealed a global view of differential metabolic change between seed and fermentation culture, and demonstrated positive correlations between transcription and expression levels of 157 differentially expressed genes involved in the metabolism of amino acids, fatty acids, secondary metabolites, antioxidant and immune responses. Facilitated by the widely targeted metabolomic approach, a total of 307 secondary substances were identified and quantified, with a significant increase in the production of antioxidant polyphenols.CONCLUSION: This study provided the comprehensive analysis of the fungus Inonotus obliquus, and supplied fundamental information for further screening of promising target metabolites and exploring the link between the genome and metabolites.PMID:37726686 | DOI:10.1186/s12864-023-09656-z

BMC Plant Biol. 2023 Sep 19;23(1):439. doi: 10.1186/s12870-023-04434-1.ABSTRACTMalva sylvestris L. (common mallow) is a plant species widely used in phytotherapy and ethnobotanical practices since time immemorial. Characterizing the components of this herb might promote a better comprehension of its biological effects on the human body but also favour the identification of the molecular processes that occur in the plant tissues. Thus, in the present contribution, the scientific knowledge about the metabolomic profile of the common mallow was expanded. In particular, the phytocomplex of leaves and flowers from this botanical species and the extraction capacity of different concentrations of ethanol (i.e., 95%, 70%, 50%, and 0%; v/v in ddH2O) for it were investigated by spectrophotometric and chromatographic approaches. In detail, 95% ethanol extracts showed the worst capacity in isolating total phenols and flavonoids, while all the hydroalcoholic samples revealed a specific ability in purifying the anthocyanins. HPLC-DAD system detected and quantified 20 phenolic secondary metabolites, whose concentration in the several extracts depended on their own chemical nature and the percentage of ethanol used in the preparation. In addition, the stability of the purified phytochemicals after resuspension in pure ddH2O was also proved, considering a potential employment of them in biological/medical studies which include in vitro and in vivo experiments on mammalian models. Here, for the first time, the expressed miRNome in M. sylvestris was also defined by Next Generation Sequencing, revealing the presence of 33 microRNAs (miRNAs), 10 typical for leaves and 2 for flowers. Then, both plant and human putative mRNA targets for the detected miRNAs were predicted by bioinformatics analyses, with the aim to clarify the possible role of these small nucleic acids in the common mallow plant tissues and to try to understand if they could exert a potential cross-kingdom regulatory activity on the human health. Surprisingly, our investigations revealed that 19 miRNAs out of 33 were putatively able to modulate, in the plant cells, the expression of various chromosome scaffold proteins. In parallel, we found, in the human transcriptome, a total of 383 mRNAs involved in 5 fundamental mammalian cellular processes (i.e., apoptosis, senescence, cell-cycle, oxidative stress, and invasiveness) that theoretically could be bound and regulated by M. sylvestris miRNAs. The evidence collected in this work would suggest that the beneficial properties of the use of M. sylvestris, documented by the folk medicine, are probably linked to their content of miRNAs and not only to the action of phytochemicals (e.g., anthocyanins). This would open new perspectives about the possibility to develop gene therapies based on miRNAs isolated from medicinal plants, including M. sylvestris.PMID:37726667 | DOI:10.1186/s12870-023-04434-1

Amino Acids. 2023 Sep 19. doi: 10.1007/s00726-023-03325-x. Online ahead of print.ABSTRACTAmino acid metabolic profile, particularly its association with clinical characteristics, remains unclear in patients with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) combined with metabolic disorders. In this study, we performed targeted metabolomic analyses on 64 patients with HIV/AIDS and 21 healthy controls. Twenty-four amino acids and selected intermediate metabolites in the serum were quantitatively detected using high-performance liquid chromatography-tandem mass spectrometry, and characteristic changes and metabolic pathways were analyzed in HIV-infected patients with different degrees of abnormal glucose and lipid metabolism. Spearman's partial correlation was used to analyze the association between amino acids, biochemical parameters, and inflammatory cytokines. The results showed that the main metabolic pathways of the eighteen differential metabolites involved were arginine biosynthesis and metabolism, methionine cycle, and tryptophan metabolism. Fourteen differential amino acid metabolites were positively correlated with nine inflammatory cytokines, including TNF-α, C-reactive protein, IL-1β, and galectin-3 (FDR < 0.1). Kynurenine, ornithine, and homocysteine were positively correlated with fasting blood glucose and insulin resistance index (FDR < 0.1). Our study revealed a multi-pathway imbalance in amino acid metabolism in patients with HIV/AIDS, which was significantly correlated with inflammation and insulin resistance.PMID:37726575 | DOI:10.1007/s00726-023-03325-x

Amino Acids. 2023 Sep 19. doi: 10.1007/s00726-023-03320-2. Online ahead of print.ABSTRACTAcne vulgaris is a chronic inflammatory disease with high incidence, diverse clinical manifestations, poor clinical efficacy, and easy recurrence. Recent studies have found that the occurrence of acne is related to metabolic factors such as insulin resistance; however, the specific mechanism of action remains unclear. This study aimed to identify significantly different metabolites and related metabolic pathways in the serum of acne vulgaris patients with or without insulin resistance. LC-MS/MS was used to analyze serum samples from patients about acne with insulin resistance (n = 51) and acne without insulin resistance (n = 69) to identify significant metabolites and metabolic pathways. In this study, 18 significant differential metabolites were screened for the first time. In the positive-ion mode, the upregulated substances were creatine, sarcosine, D-proline, uracil, Phe-Phe, L-pipecolic acid, and DL-phenylalanine; the downregulated substances were tridecanoic acid (tridecylic acid), L-lysine, cyclohexylamine, sphingomyelin (d18:1/18:0), gamma-L-Glu-epsilon-L-Lys, and 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine. In the negative-ion mode, the upregulated substance was cholesterol sulfate, and the downregulated substances were D(-)-beta-hydroxybutyric acid, myristic acid, D-galacturonic acid, and dihydrothymine. Cholesterol sulfate showed the most significant expression among all differential metabolites (VIP = 7.3411). Based on the KEGG database, necroptosis and ABC transporters were the most significantly enriched metabolic pathways in this experiment. The differential metabolites and pathways identified in this study may provide new possibilities for the clinical diagnosis and development of targeted drugs for acne patients with insulin resistance.PMID:37726574 | DOI:10.1007/s00726-023-03320-2

Sci Rep. 2023 Sep 19;13(1):15464. doi: 10.1038/s41598-023-41508-4.ABSTRACTThe critically endangered black rhinoceros (Diceros bicornis; black rhino) experiences extinction threats from poaching in-situ. The ex-situ population, which serves as a genetic reservoir against impending extinction threats, experiences its own threats to survival related to several disease syndromes not typically observed among their wild counterparts. We performed an untargeted metabolomic analysis of serum from 30 ex-situ housed black rhinos (Eastern black rhino, EBR, n = 14 animals; Southern black rhino, SBR, n = 16 animals) and analyzed differences in metabolite profiles between subspecies, sex, and health status (healthy n = 13 vs. diseased n = 14). Of the 636 metabolites detected, several were differentially (fold change > 1.5; p < 0.05) expressed between EBR vs. SBR (40 metabolites), female vs. male (36 metabolites), and healthy vs. diseased (22 metabolites). Results suggest dysregulation of propanoate, amino acid metabolism, and bile acid biosynthesis in the subspecies and sex comparisons. Assessment of healthy versus diseased rhinos indicates involvement of arachidonic acid metabolism, bile acid biosynthesis, and the pentose phosphate pathway in animals exhibiting inflammatory disease syndromes. This study represents the first systematic characterization of the circulating serum metabolome in the black rhinoceros. Findings further implicate mitochondrial and immune dysfunction as key contributors for the diverse disease syndromes reported in ex-situ managed black rhinos.PMID:37726331 | DOI:10.1038/s41598-023-41508-4

NPJ Biofilms Microbiomes. 2023 Sep 19;9(1):65. doi: 10.1038/s41522-023-00432-1.ABSTRACTIdentification of the core functional microorganisms in food fermentations is necessary to understand the ecological and functional processes for making those foods. Wheat qu, which provides liquefaction and saccharifying power, and affects the flavor quality, is a key ingredient in ancient alcoholic huangjiu fermentation, while core microbiota of them still remains indistinct. In this study, metagenomics, metabolomics, microbial isolation and co-fermentation were used to investigate huangjiu. Although Aspergillus is usually regarded as core microorganism in wheat qu to initiate huangjiu fermentations, our metagenomic analysis showed that bacteria Saccharopolyspora are predominant in wheat qu and responsible for breakdown of starch and cellulose. Metabolic network and correlation analysis showed that Saccharopolyspora rectivirgula, Saccharopolyspora erythraea, and Saccharopolyspora hirsuta made the greatest contributions to huangjiu's metabolites, consisting of alcohols (phenylethanol, isoamylol and isobutanol), esters, amino acids (Pro, Arg, Glu and Ala) and organic acids (lactate, tartrate, acetate and citrate). S. hirsuta J2 isolated from wheat qu had the highest amylase, glucoamylase and protease activities. Co-fermentations of S. hirsuta J2 with S. cerevisiae HJ resulted in a higher fermentation rate and alcohol content, and huangjiu flavors were more similar to that of traditional huangjiu compared to co-fermentations of Aspergillus or Lactiplantibacillus with S. cerevisiae HJ. Genome of S. hirsuta J2 contained genes encoding biogenic amine degradation enzymes. By S. hirsuta J2 inoculation, biogenic amine content was reduced by 45%, 43% and 62% in huangjiu, sausage and soy sauce, respectively. These findings show the utility of Saccharopolyspora as a key functional organism in fermented food products.PMID:37726290 | DOI:10.1038/s41522-023-00432-1

Environ Pollut. 2023 Sep 17:122578. doi: 10.1016/j.envpol.2023.122578. Online ahead of print.ABSTRACTHeavy metal (loid)-contaminated available arable land seriously affects crop development and growth. Engineered nanomaterials have great potential in mitigating toxic metal (loid) stress in plants. However, there are few details of nanoparticles (NPs) involved in Panax notoginseng response to cadmium (Cd) and arsenic (As). Herein, integrating physiological and metabolomic analyses, we investigated the effects of Fe3O4 NPs on plant growth and Cd/As responses in P. notoginseng. Cd/As treatment caused severe growth inhibition. However, foliar application of Fe3O4 NPs increased beneficial elements in the roots and/or leaves, decreased Cd/As content by 10.38% and 20.41% in the roots, reduced membrane damage and regulated antioxidant enzyme activity, thereby alleviating Cd/As-induced growth inhibition, as indicated by increased shoot fresh weight (FW), the rootlet length and root FW by 40.14%, 15.74%, and 46.70% under Cd stress and promoted the shoot FW by 27.00% under As toxicity. Metabolomic analysis showed that 227 and 295 differentially accumulated metabolites (DAMs) were identified, and their accumulation patterns were classified into 8 and 6 clusters in the roots and leaves, respectively. Fe3O4 NPs altered metabolites significantly involved in key pathways, including amino sugar and nucleotide sugar metabolism, flavonoid biosynthesis and phenylalanine metabolism, thus mediating the trade-off between plant growth and defense under stress. Interestingly, Fe3O4 NPs recovered more Cd/As-induced DAMs to normal levels, further supporting that Fe3O4 NPs positively affected seedling growth under metal (loid)s stress. In addition, Fe3O4 NPs altered terpenoids when the seedlings were subjected to Cd/As stress, thus affecting their potential medicinal value. This study provides insights into using nanoparticles to improve potential active ingredients of medicinal plants in metal (loid)-contaminated areas.PMID:37726032 | DOI:10.1016/j.envpol.2023.122578

Redox Biol. 2023 Sep 14;67:102888. doi: 10.1016/j.redox.2023.102888. Online ahead of print.ABSTRACTAlkyl hydroperoxide reductase (Ahp) is the primary scavenger of endogenous hydrogen peroxide in Escherichia coli (E. coli). Ahp-deficient strains have been found to have high reactive oxygen species (ROS) levels, sufficient to cause cell damage. However, the exact role and underlying mechanisms of Ahp deficiency-induced cell damage remain largely unknown. Here, the E. coli MG1655 ΔAhp mutant strain was constructed as a model of deficiency to assess its role. The cells of the ΔAhp strain were found to be significantly longer than those of the wild strain, with elevated ROS and hydrogen peroxide (H2O2) levels. Proteome, redox proteome and metabolome analyses were performed to systematically present a global and quantitative profile and delineate the redox signaling and metabolic alterations at the proteome, metabolome, and cysteine oxidation site levels. The multiomics data revealed that Ahp deficiency disrupted the redox balance, activated the OxyR system, upregulated oxidative defense proteins and inhibited the TCA cycle to some extent. Surprisingly, the mutant strain shifted from aerobic respiration to anaerobic respiration and fermentation during the logarithmic phase in the presence of sufficient O2. The acid resistance system was activated to mitigate the effect of excessive acid produced by fermentation. Taken together, the results of this study demonstrated that Ahp deficiency triggered cellular redox imbalance and regulated metabolic pathways to confer resistance to submicromolar intracellular H2O2 levels in E. coli.PMID:37725887 | DOI:10.1016/j.redox.2023.102888

J Environ Manage. 2023 Sep 17;346:118996. doi: 10.1016/j.jenvman.2023.118996. Online ahead of print.ABSTRACTNitrogen (N) fertilization is crucial to sustain global food security, but fertilizer N production is energy-demanding and subsequent environmental N losses contribute to biodiversity loss and climate change. N losses can be mitigated be interfering with microbial nitrification, and therefore the use of nitrification inhibitors in enhanced efficiency fertilizers (EEFs) is an important N management strategy to increase N use efficiency and reduce N pollution. However, currently applied nitrification inhibitors have limitations and do not target all nitrifying microorganisms. Here, to identify broad-spectrum nitrification inhibitors, we adopted a drug discovery-based approach and screened 45,400 small molecules on different groups of nitrifying microorganisms. Although a high number of potential nitrification inhibitors were identified, none of them targeted all nitrifier groups. Moreover, a high number of new nitrification inhibitors were shown to be highly effective in culture but did not reduce ammonia consumption in soil. One archaea-targeting inhibitor was not only effective in soil, but even reduced - when co-applied with a bacteria-targeting inhibitor - ammonium consumption and greenhouse gas emissions beyond what is achieved with currently applied nitrification inhibitors. This advocates for combining different types of nitrification inhibitors in EEFs to optimize N management practices and make agriculture more sustainable.PMID:37725864 | DOI:10.1016/j.jenvman.2023.118996

EBioMedicine. 2023 Sep 17;96:104802. doi: 10.1016/j.ebiom.2023.104802. Online ahead of print.ABSTRACTBACKGROUND: Patients with systemic lupus erythematosus (SLE) exhibit a high risk for cardiovascular diseases (CVD) which is not fully explained by the classical Framingham risk factors. SLE is characterized by major metabolic alterations which can contribute to the elevated prevalence of CVD.METHODS: A comprehensive analysis of the circulating metabolome and lipidome was conducted in a large cohort of 211 women with SLE who underwent a multi-detector computed tomography scan for quantification of coronary artery calcium (CAC), a robust predictor of coronary heart disease (CHD).FINDINGS: Beyond traditional risk factors, including age and hypertension, disease activity and duration were independent risk factors for developing CAC in women with SLE. The presence of coronary calcium was associated with major alterations of circulating lipidome dominated by an elevated abundance of ceramides with very long chain fatty acids. Alterations in multiple metabolic pathways, including purine, arginine and proline metabolism, and microbiota-derived metabolites, were also associated with CAC in women with SLE. Logistic regression with bootstrapping of lipidomic and metabolomic variables were used to develop prognostic scores. Strikingly, combining metabolic and lipidomic variables with clinical and biological parameters markedly improved the prediction (area under the curve: 0.887, p < 0.001) of the presence of coronary calcium in women with SLE.INTERPRETATION: The present study uncovers the contribution of disturbed metabolism to the presence of coronary artery calcium and the associated risk of CHD in SLE. Identification of novel lipid and metabolite biomarkers may help stratifying patients for reducing CVD morbidity and mortality in SLE.FUNDING: INSERM and Sorbonne Université.PMID:37725854 | DOI:10.1016/j.ebiom.2023.104802

Anal Chem. 2023 Sep 19. doi: 10.1021/acs.analchem.3c02923. Online ahead of print.ABSTRACTThe multiplicity-edited heteronuclear single quantum correlation (ME-HSQC) NMR method is widely used for the structural characterization of marine dissolved organic matter (DOM), which is a complex molecular mixture comprising millions of individual compounds. However, the standard ME-HSQC suffers from significant signal cancellation and subsequent loss of crucial structural information due to the overlap between CH3/CH (positive) and CH2 (negative) cross-peaks in overcrowded regions. This study introduces nonuniform sampling in frequency-reversed ME-HSQC (NUS FR-ME-HSQC), highlighting its remarkable potential for the comprehensive structural characterization of marine DOM. By reversing the frequency of CH2 cross-peaks into an empty region, the FR-ME-HSQC method effectively simplifies the spectra and eliminates signal cancellation. We demonstrate that nonuniform sampling enables the acquisition of comparable spectra in half the time or significantly enhances the sensitivity in time-equivalent spectra. Comparative analysis also identifies vulnerable CH2 cross-peaks in the standard ME-HSQC that coincide with CH3 and CH cross-peaks, resulting in the loss of critical structural details. In contrast, the NUS FR-ME-HSQC retains these missing correlations, enabling in-depth characterization of marine DOM. These findings highlight the potential of NUS FR-ME-HSQC as an advanced NMR technique that effectively addresses challenges such as signal overcrowding and prolonged experimental times, enabling the thorough investigation of complex mixtures with implications in several fields, including chemistry, metabolomics, and environmental sciences. The advantages of NUS FR-ME-HSQC are experimentally demonstrated on two solid-phase-extracted DOM (SPE-DOM) samples from the surface and deep ocean. With this new technology, differences in the composition of DOM from various aquatic environments can be assigned to individual molecules.PMID:37725656 | DOI:10.1021/acs.analchem.3c02923

J Am Soc Nephrol. 2023 Aug 7. doi: 10.1681/ASN.0000000000000195. Online ahead of print.ABSTRACTBACKGROUND: Hypoxia drives kidney damage and progression of CKD. Although erythrocytes respond rapidly to hypoxia, their role and the specific molecules sensing and responding to hypoxia in CKD remain unclear.METHODS: Mice with an erythrocyte-specific deficiency in equilibrative nucleoside transporter 1 (eEnt1-/-) and a global deficiency in AMP deaminase 3 (Ampd3-/-) were generated to define their function in two independent CKD models, including angiotensin II (Ang II) infusion and unilateral ureteral obstruction (UUO). Unbiased metabolomics, isotopic adenosine flux, and various biochemical and cell culture analyses coupled with genetic studies were performed. Translational studies in patients with CKD and cultured human erythrocytes examined the role of ENT1 and AMPD3 in erythrocyte function and metabolism.RESULTS: eEnt1-/- mice display severe renal hypoxia, kidney damage, and fibrosis in both CKD models. The loss of eENT1-mediated adenosine uptake reduces intracellular AMP and thus abolishes the activation of AMPKα and bisphosphoglycerate mutase (BPGM). This results in reduced 2,3-bisphosphoglycerate and glutathione, leading to overwhelming oxidative stress in eEnt1-/- mice. Excess reactive oxygen species (ROS) activates AMPD3, resulting in metabolic reprogramming and reduced O2 delivery, leading to severe renal hypoxia in eEnt1-/- mice. By contrast, genetic ablation of AMPD3 preserves the erythrocyte adenine nucleotide pool, inducing AMPK-BPGM activation, O2 delivery, and antioxidative stress capacity, which protect against Ang II-induced renal hypoxia, damage, and CKD progression. Translational studies recapitulated the findings in mice.CONCLUSION: eENT1-AMPD3, two highly enriched erythrocyte purinergic components that sense hypoxia, promote eAMPK-BPGM-dependent metabolic reprogramming, O2 delivery, energy supply, and antioxidative stress capacity, which mitigates renal hypoxia and CKD progression.PMID:37725437 | DOI:10.1681/ASN.0000000000000195

J Physiol. 2023 Sep 19. doi: 10.1113/JP285170. Online ahead of print.ABSTRACTSmall extracellular vesicles (EV) are membrane-encapsulated particles that carry bioactive cargoes, are released by all cell types and are present in all human biofluids. Changes in EV profiles and abundance occur in response to acute exercise, but this study investigated whether individuals with divergent histories of exercise training (recreationally active controls - CON; endurance-trained - END; strength-trained - STR) presented with varied abundances of small EVs in resting samples and whether the abundance of small EVs differed within each group across two measurement days. Participants (n = 38, all male; CON n = 12, END n = 13, STR n = 13) arrived at the lab on two separate occasions in a rested, overnight fasted state, with standardisation of time of day of sampling, recent dietary intake, time since last meal and time since last exercise training session (∼40 h). Whole blood samples were collected and separated into plasma from which small EVs were separated using size exclusion chromatography and identified in accordance with the Minimal Information For Studies of Extracellular Vesicles (MISEV) guidelines. No differences in the abundance of small EVs were observed within or between groups across multiple methods of small EV identification (nanoparticle tracking analysis, flow cytometry, immunoblot of specific EV markers). Targeted metabolomics of the small EV preparations identified 96 metabolites that were associated with the structure and function of small EVs, with no statistically significant differences in concentrations observed across groups. The results of the current study suggest that the abundance and metabolomic profile of small EVs derived from men with divergent histories of exercise training are similar to those in resting blood samples. KEY POINTS: Extracellular vesicles (EV) are membrane-encapsulated particles that are present in circulation and carry bioactive materials as 'cargo'. The abundance and profile of small EVs are responsive to acute exercise, but little is known about the relationship between small EVs and exercise training. This study examined the abundance, and a targeted metabolomic profile, of small EVs separated from the blood of endurance athletes, strength athletes and recreationally active controls at rest (∼40 h after the most recent exercise session) on two separate but identical lab visits. No differences were observed in the abundance or metabolomic profile of small EV preparations between the groups or between the lab visits within each group. Further research should determine whether the bioactive cargoes (e.g. RNA, protein and additional metabolites) carried within EVs are altered in individuals with divergent histories of exercise training or in response to exercise training interventions.PMID:37725436 | DOI:10.1113/JP285170

Clin Cancer Res. 2023 Sep 19. doi: 10.1158/1078-0432.CCR-23-0088. Online ahead of print.ABSTRACTPURPOSE: Lynch Syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacological intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers.EXPERIMENTAL DESIGN: To address this, we enrolled 21 LS patients onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes thrice weekly for 45 minutes versus usual care with a one-time exercise counseling session as control. We analyzed the effects of exercise on cardiorespiratory fitness, circulating, and colorectal-tissue biomarkers using metabolomics, gene expression by bulk mRNAseq, and spatial transcriptomics by NanoString GeoMx.RESULTS: We observed a significant increase in oxygen consumption (VO2peak) as a primary outcome of the exercise and a decrease in inflammatory markers (Prostaglandin E) in colon and blood as the secondary outcomes in the exercise versus usual care group. Gene expression profiling and spatial transcriptomics on available colon biopsies revealed an increase in the colonic mucosa levels of NK and CD8+ T cells in the exercise group that were further confirmed by immunohistochemical studies.CONCLUSIONS: Together these data have important implications for cancer interception in LS, and document for the first-time biological effects of exercise in the immune system of a target organ in patients at-risk for cancer.PMID:37724990 | DOI:10.1158/1078-0432.CCR-23-0088

Eur J Immunol. 2023 Sep 19:e2350536. doi: 10.1002/eji.202350536. Online ahead of print.ABSTRACTViral infections can result in metabolism rewiring of host cells, which in turn affects the viral lifecycle. Phosphoenolpyruvate (PEP), a metabolic intermediate in the glycolytic pathway, plays important roles in several biological processes including anti-tumor T cell immunity. However, whether PEP might participate in modulating viral infection remains largely unknown. Here, we demonstrate that PEP generally inhibits viral replication via upregulation of AATK expression. Targeted metabolomic analyses shown that intracellular level of PEP was increased upon viral infection. PEP treatment significantly restricted viral infection and hence declined subsequent inflammatory response both in vitro and in vivo. Besides, PEP took inhibitory effect on the stage of viral replication and also decreased the mortality of mice with viral infection. Mechanistically, PEP significantly promoted the expression of apoptosis-associated tyrosine kinase (AATK). Knockdown of AATK led to enhanced viral replication and consequent increased levels of cytokines. Moreover, AATK deficiency disabled the antiviral effect of PEP. Together, our study reveals a previously unknown role of PEP in broadly inhibiting viral replication by promoting AATK expression, highlighting the potential application of activation or upregulation of PEP-AATK axis in controlling viral infections. This article is protected by copyright. All rights reserved.PMID:37724936 | DOI:10.1002/eji.202350536

Rep Biochem Mol Biol. 2023 Apr;12(1):127-135. doi: 10.52547/rbmb.12.1.127.ABSTRACTBACKGROUND: Colorectal cancer is a heterogeneous disease that leads to metabolic disorders due to multiple upstream genetic and molecular changes and interactions. The development of new therapies, especially herbal medicines, has received much global attention. Dorema ammoniacum is a medicinal plant. Its gum is used in healing known ailments. Studying metabolome profiles based on nuclear magnetic resonance 1HNMR as a non-invasive and reproducible tool can identify metabolic changes as a reflection of intracellular fluxes, especially in drug responses. This study aimed to investigate the anti-cancer effects of different gum extracts on metabolic changes and their impact on gene expression in HT-29 cell.METHODS: Extraction of Dorema ammoniacum gum with hexane, chloroform, and dichloromethane organic solvents was performed. Cell inhibition growth percentage and IC50 were assessed. Following treating the cells with dichloromethane extract, p53, APC, and KRAS gene expression were determined. 1HNMR spectroscopy was conducted. Eventually, systems biology software tools interpreted combined metabolites and genes simultaneously.RESULTS: The lowest determined IC50 concentration was related to dichloromethane solvent, and the highest was hexane and chloroform. The expression of the KRAS oncogene gene decreased significantly after treatment with dichloromethane extract compared to the control group, and the expression of tumor suppressor gene p53 and APC increased significantly. Most gene-altered convergent metabolic phenotypes.CONCLUSION: This study's results indicate that the dichloromethane solvent of Dorema ammoniacum gum exhibits its antitumor properties by altering the expression of genes involved in HT-29 cells and the consequent change in downstream metabolic reprogramming.PMID:37724146 | PMC:PMC10505474 | DOI:10.52547/rbmb.12.1.127

Anal Bioanal Chem. 2023 Sep 18. doi: 10.1007/s00216-023-04928-9. Online ahead of print.ABSTRACTThe National Institute of Standards and Technology (NIST) has prepared four seafood reference materials (RMs) for use in food safety and nutrition studies: wild-caught and aquacultured salmon (RM 8256 and RM 8257) and wild-caught and aquacultured shrimp (RM 8258 and RM 8259). These materials were characterized using genetic, metabolomic (1H-NMR, nuclear magnetic resonance and LC-HRMS/MS, liquid chromatography high-resolution tandem mass spectrometry), lipidomic, and proteomic methods to explore their use as matrix-matched, multi-omic differential materials for method development towards identifying product source and/or as quality control in untargeted omics studies. The results from experimental replicates were reproducible for each reference material and analytical method, with the most abundant features reported. Additionally, differences between the materials could be detected, where wild-caught and aquacultured seafood could be distinguished using untargeted metabolite, lipid, and protein analyses. Further processing of the fresh-frozen RMs by freeze-drying revealed the freeze-dried seafoods could still be reliably discerned. These results demonstrate the usefulness of these reference materials as tools for omics instrument validation and measurement harmonization in seafood-related studies. Furthermore, their use as differential quality control (QC) materials, regardless of preparation method, may also provide a tool for laboratories to demonstrate proficiency at discriminating between products based on source/species.PMID:37723254 | DOI:10.1007/s00216-023-04928-9

Clin Chim Acta. 2023 Sep 16:117561. doi: 10.1016/j.cca.2023.117561. Online ahead of print.ABSTRACTBACKGROUND: We investigated alterations in the serum metabolomic profile of IgA nephropathy (IgAN) patients and screen biomarkers of IgA nephropathy based on ultra-performance liquid chromatography-mass spectrometry (UPLC-MS).METHODS: Serum samples from 65 IgAN patients and 31 healthy controls were analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Univariate and multivariate analysis were performed to screen the differential metabolites. Differential metabolites should meet both the following two criteria: adjusted P < 0.05 in the univariate analysis and VIP value > 1 in the multivariate model. Pathway analysis was performed to reveal the metabolic pathways that were significantly influenced in IgAN. Spearman correlation analysis was applied to explore the correlation between metabolites and between the metabolites and clinicopathological features of IgAN. A random forest model and Logistics regression analysis were conducted to evaluate the predictive ability of the metabolites.RESULTS: The metabolic profile was significantly altered in IgAN patients compared with healthy controls. Thirty-nine metabolites were identified, including glycerophospholipids, sphingolipids, vitamin K1, vitamin K2, bile acids and amino acids. Sphingolipid metabolism, ubiquinone and other terpenoid-quinone biosynthesis, and glycerophospholipid metabolism were found to be significantly disturbed in the pathway analysis. Differential metabolites were found to be associated with the clinical and pathological features of IgAN patients. Lanosterol, vitamin K1, vitamin K2, and β-elemonic acid were found to have promising predictive ability for IgAN.CONCLUSIONS: We confirmed the differences in the metabolic profiles of IgAN patients and healthy controls and identified the differential metabolites of IgAN, which may help with the further exploration of the pathogenesis and treatment of IgAN.PMID:37722576 | DOI:10.1016/j.cca.2023.117561

Bioresour Technol. 2023 Sep 16:129769. doi: 10.1016/j.biortech.2023.129769. Online ahead of print.ABSTRACTThe study investigated the effectiveness of magnetite and potassium ions (K+) in enhancing anaerobic digestion of high salinity food waste. Results indicated that both magnetite and K+ improved anaerobic digestion in high-salt environments, and their combination yielded even better results. The combination of magnetite and K+ promoted microorganism activity, and resulted in increased abundance of DMER64, Halobacteria and Methanosaeta. Metabolomic analysis revealed that magnetite mainly influenced quorum sensing, while K+ mainly stimulated the synthesis of compatible solutes, aiding in maintaining osmotic balance. The combined additives regulated pathways such as ATP binding cassette transport, methane metabolism, and inhibitory substance metabolism, enabling cells to resist environmental stress and maintain normal metabolic activity. Overall, this study demonstrated the potential of magnetite and K+ to enhance food waste anaerobic digestion in high salt conditions and provided valuable insights into the molecular mechanism.PMID:37722541 | DOI:10.1016/j.biortech.2023.129769

Gerontology. 2023 Sep 18. doi: 10.1159/000533789. Online ahead of print.ABSTRACTDelirium, an acute change in cognition, is common, morbid, and costly, particularly among hospitalized older adults. Despite growing knowledge of its epidemiology, far less is known about delirium pathophysiology. Initial work understanding delirium pathogenesis has focused on assaying single or a limited subset of molecules or genetic loci. Recent technological advances at the forefront of biomarker and drug target discovery have facilitated application of multiple "omics" approaches aimed to provide a more complete understanding of complex disease processes such as delirium. At its basic level, "omics" involves comparison of genes (genomics, epigenomics), transcripts (transcriptomics), proteins (proteomics), metabolites (metabolomics), or lipids (lipidomics) in biological fluids or tissues obtained from patients who have a certain condition (i.e., delirium), and those who do not. Multi-omics analyses of these various types of molecules combined with machine learning and systems biology enables the discovery of biomarkers, biological pathways, and predictors of delirium, thus elucidating its pathophysiology. This review provides an overview of the most recent omics techniques, their current impact on identifying delirium biomarkers, and future potential in enhancing our understanding of delirium pathogenesis. We summarize challenges in identification of specific biomarkers of delirium, and more importantly, in discovering the mechanisms underlying delirium pathophysiology. Based on mounting evidence, we highlight a heightened inflammatory response as one common pathway in delirium risk and progression, and we suggest other promising biological mechanisms that have recently emerged. Advanced multiple omics approaches coupled with bioinformatics methodologies have great promise to yield important discoveries that will advance delirium research.PMID:37722373 | DOI:10.1159/000533789