PubMed

Food Res Int. 2024 Jul;188:114309. doi: 10.1016/j.foodres.2024.114309. Epub 2024 Apr 25.ABSTRACTPrevious studies have demonstrated that Ligilactobacillus salivarius CCFM 1266 exhibits anti-inflammatory properties and the capability to synthesize niacin. This study aimed to investigate the fermentative abilities of L. salivarius CCFM 1266 in fermented milk. Metabonomic analysis revealed that fermentation by L. salivarius CCFM 1266 altered volatile flavor compounds and metabolite profiles, including heptanal, nonanal, and increased niacin production. Genomic investigations confirmed that L. salivarius CCFM 1266 possess essential genes for the metabolism of fructose and mannose, affirming its proficiency in utilizing fructooligosaccharides and mannan oligosaccharides. The addition of fructooligosaccharides and mannan oligosaccharides during the fermentation process significantly facilitated the proliferation of L. salivarius CCFM 1266 in fermented milk, with growth exceeding 107 colony-forming units (CFU)/mL. This intervention not only augmented the microbial density but also modified the metabolite composition of fermented milk, resulting in an elevated presence of advantageous flavor compounds such as nonanal, 2,3-pentanedione, and 3-methyl-2-butanone. However, its influence on improving the texture of fermented milk was observed to be minimal. Co-fermentation of L. salivarius CCFM 1266 with commercial fermentation starters indicated that L. salivarius CCFM 1266 was compatible, similarly altering metabolite composition and increasing niacin content in fermented milk. In summary, the findings suggest that L. salivarius CCFM 1266 holds substantial promise as an adjunctive fermentation starter, capable of enhancing the nutritional diversity of fermented milk products.PMID:38823823 | DOI:10.1016/j.foodres.2024.114309

J Biol Chem. 2024 May 30:107426. doi: 10.1016/j.jbc.2024.107426. Online ahead of print.ABSTRACTSkeletal muscle is heterogeneous tissue, composed of fast-twitch fibers primarily relying on glycolysis and slow-twitch fibers primarily relying on oxidative phosphorylation (OXPHOS). The relative expression and balance of glycolysis and oxidative phosphorylation in skeletal muscle are crucial for muscle growth and skeletal muscle metabolism. Here, we employed multi-omics approaches including transcriptomics, proteomics, phosphoproteomics, and metabolomics to unravel the role of circMYLK4, a differentially expressed circRNA in fast and slow-twitch muscle fibers, in muscle fiber metabolism. We discovered that circMYLK4 inhibits glycolysis and promotes mitochondrial oxidative phosphorylation. Mechanistically, circMYLK4 interacts with the voltage-gated calcium channel auxiliary subunit CACNA2D2, leading to the inhibition of Ca2+ release from the sarcoplasmic reticulum. The decrease in cytoplasmic Ca2+ concentration inhibits the expression of key enzymes, PHKB and PHKG1, involved in glycogen breakdown, thereby suppressing glycolysis. On the other hand, the increased fatty acid β-oxidation enhances the tricarboxylic acid (TCA) cycle and mitochondrial oxidative phosphorylation. In general, circMYLK4 plays an indispensable role in maintaining the metabolic homeostasis of skeletal muscle.PMID:38823637 | DOI:10.1016/j.jbc.2024.107426

Biochimie. 2024 May 30:S0300-9084(24)00124-X. doi: 10.1016/j.biochi.2024.05.022. Online ahead of print.ABSTRACTListeria monocytogenes is a human opportunistic foodborne pathogen that produces life-threatening infections with a high mortality rate. The control of Listeria in the food production environment and effective clinical management of human listeriosis are challenging due to the emergence of antibiotic resistance. Hence we evaluate the in vitro anti-Listeria activity of two synthetic cruzioseptins reproducing their natural sequences CZS-9, and CZS-12, and one engineered sequence based on CZS-1, named [K4K15]CZS-1. The assessment of the in vitro potential of cruzioseptins, highlighted the promising antibacterial effect of [K4K15]CZS-1 in very low concentrations (0.91 μM) and its thermal stability at high-temperature conditions, is compatible with the food industry. Microscopic and metabolomic analyses suggest cruzioseptin induces anti-Listeria bioactivity through membrane disruption and changes in the intracellular metabolome. We also report that [K4K15]CZS-1 is resistant to peptidases/proteases emphasizing a key advantage for their use as a food preservative. However, there is a need for further structural and functional optimisations for the potential clinical application as an antibiotic. In conclusion, [K4K15]CZS-1 stand out as membrane-active peptides with the ability to induce shifts in the bacteria metabolome and inspire the development of strategies for the prevention of L. monocytogenes emergence and dissemination.PMID:38823620 | DOI:10.1016/j.biochi.2024.05.022

Chem Biol Interact. 2024 May 30:111089. doi: 10.1016/j.cbi.2024.111089. Online ahead of print.ABSTRACTRadio-resistant triple negative breast cancer (TNBC) is resistant to conventional drugs and radiation therapy. ortho-topolin riboside (oTR) has been evaluated for its anticancer activity in several types of cancer cells. However, its anti-proliferative activity in radio-resistant TNBC cells has not yet been reported. Therefore, we investigated the anti-proliferative activity of oTR in radio-resistant TNBC cells, and performed metabolome, lipidome, transcriptome, and proteome profiling to reveal the mechanisms of the anticancer activity of oTR. oTR showed cytotoxicity against radio-resistant TNBC cells with an inhibitory concentration (IC50) value of 7.78 μM. Significantly decreased (p value < 0.05) basal and compensatory glycolysis were observed in the oTR-treated group than untreated group. Mitochondrial spare respiratory capacity, which is relevant to cell fitness and flexibility, was significantly decreased (p value < 0.05) in the oTR-treated group. The major metabolic pathways significantly altered by oTR according to metabolome, transcriptome, and proteome profiles were the glycerolipid/glycerophospholipid pathway (log2(FC) of MGLL = -0.13, log2(FC) of acylglycerol lipase = -1.35, log2(FC) of glycerol = -0.81), glycolysis (log2(FC) of EGLN1 = 0.16, log2(FC) of EGLN1 = 0.62, log2(FC) of glucose = -0.76, log2(FC) of lactate = -0.81), and kynurenine pathway (log2(FC) of KYNU = 0.29, log2(FC) of kynureninase = 0.55, log2(FC) of alanine = 0.72). Additionally, proline metabolism (log2(FC) of PYCR1 = -0.17, log2(FC) of proline = -0.73) was significantly altered in the metabolomic and transcriptomic profiles. The MAPK signaling pathway (log2(FC) of CCN1 = -0.15, log2(FC) of CCN family member 1 = -1.02) and Rap 1 signaling pathway (log2(FC) of PARD6B = -0.28, log2(FC) of PAR6B = -3.13) were also significantly altered in transcriptomic and proteomic profiles. The findings of this study revealed that oTR has anticancer activity in radio-resistant TNBC cells by affecting various metabolic pathways, suggesting the potential of oTR as a novel anticancer agent for radio-resistant TNBC patients.PMID:38823535 | DOI:10.1016/j.cbi.2024.111089

Protist. 2024 May 23;175(4):126044. doi: 10.1016/j.protis.2024.126044. Online ahead of print.ABSTRACTOver the past decade, the autotrophic and heterotrophic protist Euglena gracilis (E. gracilis) has gained popularity across the studies of environmental science, biosynthesis experiments, and nutritional substitutes. The unique physiology and versatile metabolism of E. gracilis have been a recent topic of interest to many researchers who continue to understand the complexity and possibilities of using E. gracilis biomolecule production. In this review, we present a comprehensive representation of recent literature outlining the various uses of biomolecules derived from E. gracilis across the fields of natural product biosynthesis, as a nutritional substitute, and as bioremediation tools. In addition, we highlight effective strategies for altering metabolite production using abiotic stressors and growth conditions. To better understand metabolite biosynthesis and its role in E. gracilis, integrated studies involving genomics, metabolomics, and proteomics should be considered. Together, we show how the ongoing advancements in E. gracilis related research continue to broaden applications in the biosynthetic sector and highlight future works that would strengthen our understanding of overall Euglena metabolism.PMID:38823247 | DOI:10.1016/j.protis.2024.126044

Food Chem. 2024 May 22;454:139798. doi: 10.1016/j.foodchem.2024.139798. Online ahead of print.ABSTRACTIngestion of fermented foods impacts human immune function, yet the bioactive food components underlying these effects are not understood. Here, we interrogated whether fermented food bioactivity relates to microbial metabolites derived from aromatic amino acids, termed aryl-lactates. Using targeted metabolomics, we established the presence of aryl-lactates in commercially available fermented foods. After pinpointing fermented food-associated lactic acid bacteria that produce high levels of aryl-lactates, we identified fermentation conditions to increase aryl-lactate production in food matrices up to 5 × 103 fold vs. standard fermentation conditions. Using ex vivo reporter assays, we found that food matrix conditions optimized for aryl-lactate production exhibited enhanced agonist activity for the human aryl-hydrocarbon receptor (AhR) as compared to standard fermentation conditions and commercial products. Reduced microbial-induced AhR activity has emerged as a hallmark of many chronic inflammatory diseases, thus we envision strategies to enhance AhR bioactivity of fermented foods to be leveraged to improve human health.PMID:38823201 | DOI:10.1016/j.foodchem.2024.139798

Int Immunopharmacol. 2024 May 31;136:112370. doi: 10.1016/j.intimp.2024.112370. Online ahead of print.ABSTRACTReperfusion after myocardial ischemia would aggravate myocardial structural and functional damage, known as myocardial ischemia-reperfusion (MI/R) injury. Cinnamamide derivatives have been reported to exert cardioprotective effects, and we have previously reported that compound 7 played a role in cardioprotection against MI/R via anti-inflammatory effect. However, exact mechanism underlying such beneficial action of compound 7 is still unclear. The protective effect of compound 7 was determined in H9c2 cells under H2O2 stimulation with or without nigerin (NLRP3 activator). Electrocardiogram, echocardiography, myocardial infarction size, histopathology and serum biochemical assay were performed in MI/R rats. Metabolomics in vivo and mRNA or protein levels of NLRP3, ASC, cleaved caspase-1 and its downstream IL-18 and IL-1β were detected both in vitro and in vivo. Compound 7 significantly ameliorate H2O2-induced cardiomyocyte damage, which was supported by in vivo data determined by improved left ventricular systolic function and histopathological changes, reduced myocardial infarction area and cellular apoptosis in heart tissue. Cardiac differential metabolites demonstrated that compound 7 indeed altered the cardiac reprogramming of inflammation-related metabolites, which was evidenced by down-regulated cardiac inflammation by compound 7. Additionally, compound 7 alleviated myocardial injury by inhibiting the NLRP3 pathway rather than other members of the inflammasome both in vitro and in vivo, which was further evidenced by CETSA assay. Whereas, nigerin blocked the inhibitory activity of compound 7 against NLRP3. Cinnamamide derivative compound 7 ameliorated MI/R injury by inhibiting inflammation via NLRP3.PMID:38823174 | DOI:10.1016/j.intimp.2024.112370

Food Chem. 2024 May 27;455:139857. doi: 10.1016/j.foodchem.2024.139857. Online ahead of print.ABSTRACTMelatonin acts as a potential regulator of cadmium (Cd) tolerance in rice. However, its practical value in rice production remains unclear. To validate the hypothesis that melatonin affects Cd accumulation and rice quality, a series of experiments were conducted. The results showed that exogenous melatonin application was associated with reduced Cd accumulation (23-43%) in brown rice. Fourier transform infrared spectroscopy (FTIR) analysis showed that exogenous melatonin affected the rice protein secondary structure and starch short-range structure. Metabolomics based on LC-MS/MS revealed that exogenous melatonin altered the brown rice metabolic profile, decreased fatty acid metabolite content, but increased amino acid metabolite, citric acid, melatonin biosynthetic metabolite, and plant hormone contents. These findings indicate that exogenous melatonin can effectively reduced Cd accumulation and improve rice quality through metabolic network regulation, serving as an effective treatment for rice cultivated in Cd-contaminated soil.PMID:38823141 | DOI:10.1016/j.foodchem.2024.139857

Plant Physiol Biochem. 2024 May 22;212:108770. doi: 10.1016/j.plaphy.2024.108770. Online ahead of print.ABSTRACTCadmium (Cd) and lead (Pb) are among the most toxic heavy metals affecting human health and crop yield. Suaeda maritima (L.) Dumort is an obligate halophyte that is well adapted to saline soil. The inbuilt salinity tolerance mechanisms of halophytes help them to survive in heavy metal-contaminated rhizospheric soil. In the present study, growth and ionomic responses, reactive oxygen species (ROS) accumulation, modulations of phytochelatins, antioxidative defense, and metabolomic responses were studied in S. maritima imposed to Cd and Pb stresses with an aim to elucidate Cd and Pb tolerance mechanisms and phytoremediation potential of this halophyte. Our results showed a reduction of biomass in S. maritima, which may serve as an energy conservation strategy for survival under heavy metal stress. The increased accumulation of ROS with concomitant higher expression of various antioxidative enzymes suggests the efficient scavenging of ROS. The metabolite profiling revealed significant up-regulation of sugars, sugar alcohols, amino acids, polyphenols, and organic acids under Cd and Pb stresses suggesting their possible role in osmotic balance, ionic homeostasis, ROS scavenging, and signal transduction for stress tolerance. In S. maritima, the translocation factors (Tf) are <1 in both Cd and Pb treatments, which indicates that this halophyte has high phytostabilization potential for Cd and Pb in roots and through restricted translocation of heavy metal ions to the aboveground part. The findings of this study offer comprehensive information on Cd and Pb tolerance mechanisms in S. maritima and suggest that this halophyte can detoxify the HMs through physiological, ionic, antioxidative, and metabolic regulations.PMID:38823092 | DOI:10.1016/j.plaphy.2024.108770

J Anim Sci Biotechnol. 2024 Jun 1;15(1):71. doi: 10.1186/s40104-024-01034-3.ABSTRACTBACKGROUND: The hypothalamus plays a crucial role in the health and productivity of dairy cows, yet studies on its functionality and its impact on peripheral circulation in these animals are relatively scarce, particularly regarding dietary interventions. Therefore, our study undertook a comprehensive analysis, incorporating both metabolomics and transcriptomics, to explore the effects of a grain-based diet on the functionality of the hypothalamus, as well as on blood and milk in dairy cows.RESULTS: The hypothalamic metabolome analysis revealed a significant reduction in prostaglandin E2 (PGE2) level as a prominent response to the grain-based diet introduction. Furthermore, the hypothalamic transcriptome profiling showed a notable upregulation in amino acid metabolism due to the grain-based diet. Conversely, the grain-based diet led to the downregulation of genes involved in the metabolic pathway from lecithin to PGE2, including phospholipase A2 (PLA2G4E, PLA2G2A, and PLA2G12B), cyclooxygenase-2 (COX2), and prostaglandin E synthase (PTGES). Additionally, the plasma metabolome analysis indicated a substantial decrease in the level of PGE2, along with a decline in adrenal steroid hormones (tetrahydrocortisol and pregnenolone) following the grain-based diet introduction. Analysis of the milk metabolome showed that the grain-based diet significantly increased uric acid level while notably decreasing PGE2 level. Importantly, PGE2 was identified as a critical metabolic marker in the hypothalamus, blood, and milk in response to grain intervention. Correlation analysis demonstrated a significant correlation among metabolic alterations in the hypothalamus, blood, and milk following the grain-based diet.CONCLUSIONS: Our findings suggest a potential link between hypothalamic changes and alterations in peripheral circulation resulting from the introduction of a grain-based diet.PMID:38822422 | DOI:10.1186/s40104-024-01034-3

J Transl Med. 2024 May 31;22(1):525. doi: 10.1186/s12967-024-05312-6.ABSTRACTAcetaminophen (APAP)-induced liver injury (AILI) is a pressing public health concern. Although evidence suggests that Bifidobacterium adolescentis (B. adolescentis) can be used to treat liver disease, it is unclear if it can prevent AILI. In this report, we prove that B. adolescentis significantly attenuated AILI in mice, as demonstrated through biochemical analysis, histopathology, and enzyme-linked immunosorbent assays. Based on untargeted metabolomics and in vitro cultures, we found that B. adolescentis generates microbial metabolite hypaphorine. Functionally, hypaphorine inhibits the inflammatory response and hepatic oxidative stress to alleviate AILI in mice. Transcriptomic analysis indicates that Cry1 expression is increased in APAP-treated mice after hypaphorine treatment. Overexpression of Cry1 by its stabilizer KL001 effectively mitigates liver damage arising from oxidative stress in APAP-treated mice. Using the gene expression omnibus (GEO) database, we verified that Cry1 gene expression was also decreased in patients with APAP-induced acute liver failure. In conclusion, this study demonstrates that B. adolescentis inhibits APAP-induced liver injury by generating hypaphorine, which subsequently upregulates Cry1 to decrease inflammation and oxidative stress.PMID:38822329 | DOI:10.1186/s12967-024-05312-6

Cancer Cell Int. 2024 May 31;24(1):192. doi: 10.1186/s12935-024-03342-0.ABSTRACTBACKGROUND: Immunotherapy combined with molecular targeted therapy is increasingly popular in patients with advanced hepatocellular carcinoma (HCC). However, immune-related adverse events(irAEs) brought on by immunotherapy increase the likelihood of side effects, thus it is important to look into ways to address this issue.METHODS: Different metabolite patterns were established by analyzing metabolomics data in liver tissue samples from 10 patients(divided into severe and mild liver injury) before and after immuno-targeted therapy. After establishing a subcutaneous tumor model of HCC, the mice were divided into PBS group, ascorbic acid(AA) group, and anti-PD1 + tyrosine kinase inhibitor (TKI) group, anti-PD1 + TKI + AA group. Liver tissue were stained with hematoxylin-eosin staining(HE) and the content of aspartate transaminase (AST) and alanine transaminase(ALT) in blood were determined. The mechanism was confirmed by western blotting, mass cytometry, and other techniques.RESULTS: Through metabolomics analysis, AA was significantly reduced in the sample of patients with severe liver injury caused by immuno-targeted therapy compared to patients with mild liver injury. The addition of AA in vivo experiments demonstrated a reduction in liver injury in mice. In the liver tissues of the anti-PD1 + TKI + AA group, the protein expressions of SLC7A11,GPX4 and the level of glutathione(GSH) were found to be higher compared to the anti-PD1 + TKI group. Mass cytometry analysis revealed a significant increase in the CD11b+CD44+ PD-L1+ cell population in the AA group when compared to the PBS group.CONCLUSIONS: AA could reduce liver injury by preventing hepatocyte SLC7A11/GPX4 ferroptosis and improve the immunotherapy effect of anti-PD1 by boosting CD11b+CD44+PD-L1+cell population in HCC.PMID:38822322 | DOI:10.1186/s12935-024-03342-0

BMC Plant Biol. 2024 May 31;24(1):482. doi: 10.1186/s12870-024-05204-3.ABSTRACTAnabasis aphylla (A. aphylla), a species of the Amaranthaceae family, is widely distributed in northwestern China and has high pharmacological value and ecological functions. However, the growth characteristics are poorly understood, impeding its industrial development for biopesticide development. Here, we explored the regenerative capacity of A. aphylla. To this end, different lengths of the secondary branches of perennial branches were mowed at the end of March before sprouting. The four treatments were no mowing (M0) and mowing 1/3, 2/3, and the entire length of the secondary branches of perennial branches (M1-M3, respectively). Next, to evaluate the compensatory growth after mowing, new assimilate branches' related traits were recorded every 30 days, and the final biomass was recorded. The mowed plants showed a greater growth rate of assimilation branches than un-mowed plants. Additionally, with the increasing mowing degree, the growth rate and the final biomass of assimilation branches showed a decreasing trend, with the greatest growth rate and final biomass in response to M1. To evaluate the mechanism of the compensatory growth after mowing, a combination of dynamic (0, 1, 5, and 8 days after mowing) plant hormone-targeted metabolomics and transcriptomics was performed for the M0 and M1 treatment. Overall, 26 plant hormone metabolites were detected, 6 of which significantly increased after mowing compared with control: Indole-3-acetyl-L-valine methyl ester, Indole-3-carboxylic acid, Indole-3-carboxaldehyde, Gibberellin A24, Gibberellin A4, and cis (+)-12-oxo-phytodienoic acid. Additionally, 2,402 differentially expressed genes were detected between the mowed plants and controls. By combining clustering analysis based on expression trends after mowing and gene ontology analysis of each cluster, 18 genes related to auxin metabolism were identified, 6 of which were significantly related to auxin synthesis. Our findings suggest that appropriate mowing can promote A. aphylla growth, regulated by the auxin metabolic pathway, and lays the foundation for the development of the industrial value of A. aphylla.PMID:38822275 | DOI:10.1186/s12870-024-05204-3

Chem Biodivers. 2024 May 31:e202400679. doi: 10.1002/cbdv.202400679. Online ahead of print.ABSTRACTBanisteriopsis (Malpighiaceae) is an important genus of neotropical savannas with related biological and medicinal activities but under-explored metabolomic profiles. We present a chemometric analysis for discriminating secondary metabolites of three species of Banisteriopsis (B. laevifolia, B. malifolia, and B. stellaris) leaves. Initially, each species was separately extracted with ethanol:water (4:1, v/v) and analysed by Ultra Performance Liquid Chromatography coupled with Mass Spectrometry (UPLC-MS/MS). The chromatographic profiles were subjected to Global Natural Product Social (GNPS) and Partial Least Squares Discriminant Analysis (PLS-DA). Eighty-nine compounds (cosine ≥ 0.90) were annotated, including flavonoids, phenolics, and acids. The chemometric analysis (VIP Score) showed each species' relative concentration of the more relevant compounds. In addition, four compounds that discriminate the metabolomic profiles of B. laevifolia, B. malifolia, and B. stellaris were identified by PLS-DA.PMID:38822223 | DOI:10.1002/cbdv.202400679

Sci Rep. 2024 May 31;14(1):12546. doi: 10.1038/s41598-024-63181-x.ABSTRACTNanosecond pulsed electric field (nsPEF) has emerged as a promising approach for inducing cell death in melanoma, either as a standalone treatment or in combination with chemotherapeutics. However, to date, there has been a shortage of studies exploring the impact of nsPEF on the expression of cancer-specific molecules. In this investigation, we sought to assess the effects of nsPEF on melanoma-specific MAGE (Melanoma Antigen Gene Protein Family) expression. To achieve this, melanoma cells were exposed to nsPEF with parameters set at 8 kV/cm, 200 ns duration, 100 pulses, and a frequency of 10 kHz. We also aimed to comprehensively describe the consequences of this electric field on melanoma cells' invasion and proliferation potential. Our findings reveal that following exposure to nsPEF, melanoma cells release microvesicles containing MAGE antigens, leading to a simultaneous increase in the expression and mRNA content of membrane-associated antigens such as MAGE-A1. Notably, we observed an unexpected increase in the expression of PD-1 as well. While we did not observe significant differences in the cells' proliferation or invasion potential, a remarkable alteration in the cells' metabolomic and lipidomic profiles towards a less aggressive phenotype was evident. Furthermore, we validated these results using ex vivo tissue cultures and 3D melanoma culture models. Our study demonstrates that nsPEF can elevate the expression of membrane-associated proteins, including melanoma-specific antigens. The mechanism underlying the overexpression of MAGE antigens involves the initial release of microvesicles containing MAGE antigens, followed by a gradual increase in mRNA levels, ultimately resulting in elevated expression of MAGE antigens post-experiment. These findings shed light on a novel method for modulating cancer cells to overexpress cancer-specific molecules, thereby potentially enhancing their sensitivity to targeted anticancer therapy.PMID:38822068 | DOI:10.1038/s41598-024-63181-x

Nat Metab. 2024 May 31. doi: 10.1038/s42255-024-01053-4. Online ahead of print.ABSTRACTOxygen is critical for all metazoan organisms on the earth and impacts various biological processes in physiological and pathological conditions. While oxygen-sensing systems inducing acute hypoxic responses, including the hypoxia-inducible factor pathway, have been identified, those operating in prolonged hypoxia remain to be elucidated. Here we show that pyridoxine 5'-phosphate oxidase (PNPO), which catalyses bioactivation of vitamin B6, serves as an oxygen sensor and regulates lysosomal activity in macrophages. Decreased PNPO activity under prolonged hypoxia reduced an active form of vitamin B6, pyridoxal 5'-phosphate (PLP), and inhibited lysosomal acidification, which in macrophages led to iron dysregulation, TET2 protein loss and delayed resolution of the inflammatory response. Among PLP-dependent metabolism, supersulfide synthesis was suppressed in prolonged hypoxia, resulting in the lysosomal inhibition and consequent proinflammatory phenotypes of macrophages. The PNPO-PLP axis creates a distinct layer of oxygen sensing that gradually shuts down PLP-dependent metabolism in response to prolonged oxygen deprivation.PMID:38822028 | DOI:10.1038/s42255-024-01053-4

NPJ Syst Biol Appl. 2024 May 31;10(1):63. doi: 10.1038/s41540-024-00382-0.ABSTRACTYeast metabolism can be engineered to produce xenobiotic compounds, such as cannabinoids, the principal isoprenoids of the plant Cannabis sativa, through heterologous metabolic pathways. However, yeast cell factories continue to have low cannabinoid production. This study employed an integrated omics approach to investigate the physiological effects of cannabidiol on S. cerevisiae CENPK2-1C yeast cultures. We treated the experimental group with 0.5 mM CBD and monitored CENPK2-1C cultures. We observed a latent-stationary phase post-diauxic shift in the experimental group and harvested samples in the inflection point of this growth phase for transcriptomic and metabolomic analysis. We compared the transcriptomes of the CBD-treated yeast and the positive control, identifying eight significantly overexpressed genes with a log fold change of at least 1.5 and a significant adjusted p-value. Three notable genes were PDR5 (an ABC-steroid and cation transporter), CIS1, and YGR035C. These genes are all regulated by pleiotropic drug resistance linked promoters. Knockout and rescue of PDR5 showed that it is a causal factor in the post-diauxic shift phenotype. Metabolomic analysis revealed 48 significant spectra associated with CBD-fed cell pellets, 20 of which were identifiable as non-CBD compounds, including fatty acids, glycerophospholipids, and phosphate-salvage indicators. Our results suggest that mitochondrial regulation and lipidomic remodeling play a role in yeast's response to CBD, which are employed in tandem with pleiotropic drug resistance (PDR). We conclude that bioengineers should account for off-target product C-flux, energy use from ABC-transport, and post-stationary phase cell growth when developing cannabinoid-biosynthetic yeast strains.PMID:38821949 | DOI:10.1038/s41540-024-00382-0

Clin Chim Acta. 2024 May 29:119753. doi: 10.1016/j.cca.2024.119753. Online ahead of print.ABSTRACTIrritable bowel syndrome (IBS) is a chronic gastrointestinal (GI) disorder characterized by altered bowel habits and abdominal discomfort during defecation. It significantly impacts life quality and work productivity for those affected. Global data suggests a slightly higher prevalence in females than in males. Today, unambiguous diagnosis of IBS remains challenging due to the absence of a specific biochemical, histopathological, or radiological test. Current diagnosis relies heavily on thorough symptom evaluation. Recent efforts by the Rome committees have established standardized diagnostic criteria (Rome I-IV), improving consistency and clinical applicability. Recent studies in this framework, seem to have successfully employed metabolomics techniques to identify distinct metabolite profiles in breath and stool samples of IBS patients, differentiating them from healthy controls and those with other functional GI disorders, such as inflammatory bowel disease (IBD). Building on this success, researchers are investigating the presence of similar metabolites in easily accessible biofluids such as urine, potentially offering a less invasive diagnostic approach. Accordingly, this review focuses on key metabolites specifically detected in IBS patients' biological specimens, with a focus on urinary metabolites, using various methods, particularly mass spectrometry (MS)-based techniques, including gas chromatography-MS (GC-MS), liquid chromatography-tandem MS (LC-MS/MS), and capillary electrophoresis-MS (CE-MS) metabolomics assays. These findings may make provision for a new set of non-invasive biomarkers for IBS diagnosis and management.PMID:38821336 | DOI:10.1016/j.cca.2024.119753

Sci Total Environ. 2024 May 29:173624. doi: 10.1016/j.scitotenv.2024.173624. Online ahead of print.ABSTRACTWhile organisms have evolved to cope with predictable changes in the environment, the rapid rate of current global change presents numerous novel and unpredictable stressors to which organisms have had less time to adapt. To persist in the urban environment, organisms must modify their physiology, morphology and behaviour accordingly. Metabolomics offers great potential for characterising organismal responses to natural and anthropogenic stressors at the systems level and can be applied to any species, even without genomic knowledge. Using metabolomic profiling of blood, we investigated how two closely related species of passerine bird respond to the urban environment. Great tits Parus major and blue tits Cyanistes caeruleus residing in urban and forest habitats were sampled during the breeding (spring) and non-breeding (winter) seasons across replicated sites in southern Sweden. During breeding, differences in the plasma metabolome between urban and forest birds were characterised by higher levels of amino acids in urban-dwelling tits and higher levels of fatty acyls in forest-dwelling tits. The suggested higher rates of fatty acid oxidation in forest tits could be driven by habitat-associated differences in diet and could explain the higher reproductive investment and success of forest tits. High levels of amino acids in breeding urban tits could reflect the lack of lipid-rich caterpillars in the urban environment and a diet switch to protein-rich spiders, which could offer an advantage in tackling inflammation and oxidative stress associated with pollution. In winter, metabolomic profiles indicated lower overall levels of amino acids and fatty acyls in urban tits, which could reflect relaxed energetic demands in the urban environment. Our metabolomic profiling of two urban-adapted species suggests that their metabolism is modified by urban living, though whether these changes represent adaptations or are non-adaptive mechanisms to cope with anthropogenic challenges remains to be determined.PMID:38821291 | DOI:10.1016/j.scitotenv.2024.173624

J Chromatogr A. 2024 May 22;1728:465015. doi: 10.1016/j.chroma.2024.465015. Online ahead of print.ABSTRACTCharacterization studies of the plant metabolome are crucial for revealing plant physiology, developing functional foods, and controlling quality. Mass spectrometry-based metabolite profiling allows unprecedented qualitative coverage of complex biological extract composition. However, the electrospray ionization used in metabolite profiling generates multiple artifactual signals for a single analyte, which makes it challenging to filter out redundant signals and organize the signals corresponding to abundant constituents. This study proposed a strategy integrating in-source fragments elimination, diagnostic ions recognition, and feature-based molecular networking (ISFE-DIR-FBMN) to simultaneously characterize cycloartane triterpenoids (CTs) from three medicinal Cimicifuga species. The results showed that 63.1 % of the measured ions were redundant. A total of 184 CTs were annotated, with 27.1 % being reported for the first time. It presents a promising approach to assess the composition of natural extracts, thus facilitating new ingredient registrations or natural-extracts-based drug discovery campaigns. Besides, chemometrics analysis of the three Cimicifuga species identified 32 species-specific markers, highlighting significant differences among them. The valuable information can enhance the sustainable utilization and further development of Cimicifuga resources. The codes involved in ISFE-DIR-FBMN are freely available on GitHub (https://github.com/LHJ-Group/ISFE-DIR-FBMN.git).PMID:38821032 | DOI:10.1016/j.chroma.2024.465015