Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Serum metabolic signatures for acute pulmonary embolism identified by untargeted metabolomics

Mon, 19/06/2023 - 12:00
Front Med (Lausanne). 2023 Jun 2;10:1169038. doi: 10.3389/fmed.2023.1169038. eCollection 2023.ABSTRACTBACKGROUND AND AIMS: The important metabolic features of acute pulmonary embolism (APE) risk stratification and their underlying biological basis remain elusive. Our study aims to develop early diagnostic models and classification models by analyzing the plasma metabolic profile of patients with APE.MATERIALS AND METHODS: Serum samples were collected from 68 subjects, including 19 patients with confirmed APE, 35 patients with confirmed NSTEMI, and 14 healthy individuals. A comprehensive metabolic assessment was performed using ultra-performance liquid chromatography-mass spectrometry based on an untargeted metabolomics approach. In addition, an integrated machine learning strategy based on LASSO and logistic regression was used for feature selection and model building.RESULTS: The metabolic profiles of patients with acute pulmonary embolism and NSTEMI is significantly altered relative to that of healthy individuals. KEGG pathway enrichment analysis revealed differential metabolites between acute pulmonary embolism and healthy individuals mainly involving glycerophosphate shuttle, riboflavin metabolism, and glycerolipid metabolism. A panel of biomarkers was defined to distinguish acute pulmonary embolism, NSTEMI, and healthy individuals with an area under the receiver operating characteristic curve exceeding 0.9 and higher than that of D-dimers.CONCLUSION: This study contributes to a better understanding of the pathogenesis of APE and facilitates the discovery of new therapeutic targets. The metabolite panel can be used as a potential non-invasive diagnostic and risk stratification tool for APE.PMID:37332756 | PMC:PMC10272531 | DOI:10.3389/fmed.2023.1169038

Shotgun lipidomics reveals the changes in phospholipids of brown rice during accelerated aging

Sun, 18/06/2023 - 12:00
Food Res Int. 2023 Sep;171:113073. doi: 10.1016/j.foodres.2023.113073. Epub 2023 Jun 2.ABSTRACTBrown rice exhibits higher nutritional value and attracts more and more attentions; however, the change in phospholipid molecular species in brown rice during aging is poorly understood. In this study, shotgun lipidomics was employed to investigate the changes in phospholipid molecular species in four brown rice varieties (two japonica rice and two indica rice) during accelerated aging. A total of 64 phospholipid molecular species were identified, and most of them were rich in polyunsaturated fatty acids. For japonica rice, phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylglycerol (PG) gradually decreased during accelerated aging. However, the content of PC, PE, and PG in indica rice showed no difference during accelerated aging. Significantly different phospholipid molecular species from four brown rice were screened during accelerated aging. Based on these significantly different phospholipids, the metabolic pathways including glycerophospholipid metabolism and linoleic acid metabolism during accelerated aging were depicted. The findings from this study could be helpful in explaining the impact of accelerated aging on phospholipids of brown rice, and offer an understanding on relationships between phospholipids degradation and brown rice deterioration.PMID:37330832 | DOI:10.1016/j.foodres.2023.113073

Improvement of the functional value of green soybean (edamame) using germination and tempe fermentation: A comparative metabolomics study

Sun, 18/06/2023 - 12:00
J Biosci Bioeng. 2023 Jun 16:S1389-1723(23)00145-7. doi: 10.1016/j.jbiosc.2023.05.012. Online ahead of print.ABSTRACTGreen soybean, also known as edamame, is a legume with high nutritional and functional value. Despite its growing popularity and potential health benefits, the functionality of green soybean has not been thoroughly studied. Previous research on the functionality of green soybean has largely focused on a limited number of specific, well-studied, bioactive metabolites, without comprehensively investigating the metabolome of this legume. Additionally, very few studies have explored the improvement of the functional value of green soybean. This study aimed to investigate the metabolome profile of green soybean, identify bioactive metabolites, and to further explore the potential improvement of the identified bioactive metabolites using germination and tempe fermentation. A total of 80 metabolites were annotated from green soybean using GC-MS and HPLC-PDA-MS. Among them, 16 important bioactive metabolites were identified: soy isoflavones daidzin, glycitin, genistin, malonyl daidzin, malonyl genistin, malonyl glycitin, acetyl daidzin, acetyl genistin, acetyl glycitin, daidzein, glycitein, and genistein, as well as other metabolites including 3,4-dihydroxybenzoic acid, 3-hydroxyanthranillic acid, 3-hydroxy-3-methylglutaric acid (meglutol), and 4-aminobutyric acid (GABA). Germination and tempe fermentation techniques were employed to potentially improve the concentrations of these bioactive metabolites. While showing improvements in amino acid contents, germination process did not improve bioactive metabolites significantly. In contrast, tempe fermentation was found to significantly increase the concentrations of daidzein, genistein, glycitein, acetyl genistin, acetyl daidzin, 3-hydroxyanthranillic acid, and meglutol (>2-fold increase with p < 0.05) while also improving amino acid levels. This study highlights the potentials of germination and fermentation to improve the functionality of legumes, particularly green soybean.PMID:37331843 | DOI:10.1016/j.jbiosc.2023.05.012

Blood Oxylipin Profiles as Markers of Oncological Diseases

Sun, 18/06/2023 - 12:00
Biochemistry (Mosc). 2023 May;88(5):621-629. doi: 10.1134/S000629792305005X.ABSTRACTOxylipins are signal lipid molecules formed from polyunsaturated fatty acids (PUFAs) in several multienzymatic metabolic pathways, such as cyclooxygenase (COX), lipoxygenase (LOX), epoxygenase (CYP), and anandamide pathways, as well as non-enzymatically. The pathways of PUFA transformation are activated in parallel, yielding a mixture of physiologically active substances. Although the association of oxylipins with carcinogenesis had been established a long time ago, only recently analytical methods have advanced to a degree allowing detection and quantification of oxylipins from different classes (oxylipin profiles). The review describes current approaches to the HPLC-MS/MS analysis of oxylipin profiles and compares oxylipin profiles from patients with oncological diseases (breast cancer, colorectal cancer, ovarian cancer, lung cancer, prostate cancer, liver cancer). The possibility of using blood oxylipin profiles as biomarkers in oncological diseases is discussed. Understanding the patterns of PUFA metabolism and physiological activity of combinations of oxylipins will improve early diagnostics of oncological diseases and evaluation of disease prognosis.PMID:37331708 | DOI:10.1134/S000629792305005X

Metabolic disturbances in the gut-brain axis of a mouse model of MPTP-induced Parkinsonism evaluated by Nuclear Magnetic Resonance

Sun, 18/06/2023 - 12:00
Neuroscience. 2023 Jun 16:S0306-4522(23)00266-X. doi: 10.1016/j.neuroscience.2023.06.010. Online ahead of print.ABSTRACTParkinson's Disease is a synucleinopathy that primarily affects the dopaminergic cells of the central nervous system, leading to motor and gastrointestinal disturbances. However, intestinal peripheral neurons undergo a similar neurodegeneration process, marked by α-synuclein (αSyn) accumulation and loss of mitochondrial homeostasis. We investigated the metabolic alterations in different biometrics that compose the gut-brain axis (blood, brain, large intestine, and feces) in an MPTP-induced mouse model of sporadic Parkinson's Disease. Animals received escalating administration of MPTP. Tissues and fecal pellets were collected, and the metabolites were identified through the untargeted Nuclear Magnetic Resonance spectroscopic (1H NMR) technique. We found differences in many metabolites from all the tissues evaluated. The differential expression of metabolites in these samples mainly reflects inflammatory aspects, cytotoxicity, and mitochondrial impairment (oxidative stress and energy metabolism) in the animal model used. The direct evaluation of fecal metabolites revealed changes in several classes of metabolites. This data reinforces previous studies showing that Parkinson's disease is associated with metabolic perturbation not only in brain-related tissues, but also in periphery structures such as the gut. In addition, the evaluation of the microbiome and metabolites from gut and feces emerge as promising sources of information for understanding the evolution and progression of sporadic Parkinson's Disease.PMID:37331688 | DOI:10.1016/j.neuroscience.2023.06.010

Metabolic rewiring and epigenetic reprogramming in leptin receptor-deficient db/db diabetic nephropathy mice

Sun, 18/06/2023 - 12:00
Eur J Pharmacol. 2023 Jun 16:175866. doi: 10.1016/j.ejphar.2023.175866. Online ahead of print.ABSTRACTBACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in the United States. Emerging evidence suggests that mitochondrial metabolism and epigenetics play an important role in the development and progression of DN and its complications. For the first time, we investigated the regulation of cellular metabolism, DNA methylation, and transcriptome status by high glucose (HG) in the kidney of leptin receptor-deficient db/db mice using multi-omics approaches.METHODS: The metabolomics was performed by liquid-chromatography-mass spectrometry (LC-MS), while epigenomic CpG methylation coupled with transcriptomic gene expression was analyzed by next-generation sequencing.RESULTS: LC-MS analysis of glomerular and cortex tissue samples of db/db mice showed that HG regulated several cellular metabolites and metabolism-related signaling pathways, including S-adenosylmethionine, S-adenosylhomocysteine, methionine, glutamine, and glutamate. Gene expression study by RNA-seq analysis suggests transforming growth factor beta 1 (TGFβ1) and pro-inflammatory pathways play important roles in early DN. Epigenomic CpG methyl-seq showed HG revoked a list of differentially methylated regions in the promoter region of the genes. Integrated analysis of DNA methylation in the promoter regions of genes and gene expression changes across time points identified several genes persistently altered in DNA methylation and gene expression. Cyp2d22, Slc1a4, and Ddah1 are some identified genes that could reflect dysregulated genes involved in renal function and DN.CONCLUSION: Our results suggest that leptin receptor deficiency leading to HG regulates metabolic rewiring, including SAM potentially driving DNA methylation and transcriptomic signaling that could be involved in the progression of DN.PMID:37331680 | DOI:10.1016/j.ejphar.2023.175866

Activation of AMPKα2 attenuated doxorubicin-induced cardiotoxicity via inhibiting lipid peroxidation associated ferroptosis

Sun, 18/06/2023 - 12:00
Free Radic Biol Med. 2023 Jun 16:S0891-5849(23)00486-0. doi: 10.1016/j.freeradbiomed.2023.06.004. Online ahead of print.ABSTRACTFerroptosis has been suggested to involve in doxorubicin (DOX)-induced cardiotoxicity. However, the underlying mechanisms and regulatory targets of cardiomyocyte ferroptosis remains to be understood. This study demonstrated that the up-regulation of ferroptosis associated proteins genes were accompanied with the down-regulation of AMPKα2 phosphorylation in DOX treated mouse heart or neonatal rat cardiomyocytes (NRCMs). AMPKα2 knockout (AMPKα2-/-) significantly exacerbated mouse cardiac dysfunction, increased mortality, promoting ferroptosis associated mitochondrial injuries, enhanced ferroptosis associated proteins and genes expression, and lead to accumulation of lactate dehydrogenase (LDH) and malondialdehyde (MDA) in mouse serum and hearts respectively. Ferrostatin-1 administration markedly improved cardiac function, decreased mortality, inhibited mitochondrial injuries and ferroptosis associated proteins and genes expression, and depressed accumulation of LDH and MDA in DOX treated AMPKα2-/- mouse. Moreover, Adeno-associated virus serotype 9 AMPKα2 (AAV9-AMPKα2) or AICAR treatment mediated AMPKα2 activation could significantly improve cardiac function and depress ferroptosis in mouse. AMPKα2 activation or silence could also inhibit or promote ferroptosis associated injuries in DOX treated NRCMs respecitively. Mechanistically, AMPKα2/ACC mediated lipid metabolism has been suggested to involve in regulating DOX-treatment induced ferroptosis other than mTORC1 or autophagy dependent pathway. The metabolomics analysis exhibited that AMPKα2-/- significantly enhanced accumulation of polyunsaturated fatty acids (PFAs), oxidized lipid, and phosphatidylethanolamine (PE). Finally, this study also demonstrated that metformin (MET) treatment could inhibit ferroptosis and improve cardiac function via activating AMPKα2 phosphorylation. The metabolomics analysis exhibited that MET treatment significantly depressed PFAs accumulation in DOX treated mouse hearts. Collectively, this study suggested that AMPKα2 activation might protect against anthracycline chemotherapeutic drugs mediated cardiotoxicity via inhibiting ferroptosis.PMID:37331642 | DOI:10.1016/j.freeradbiomed.2023.06.004

A combined proteomics and metabolomics analysis reveals the invisible regulation of plant root responses to oxybenzone (benzophenone-3) stress

Sun, 18/06/2023 - 12:00
Sci Total Environ. 2023 Jun 16:164951. doi: 10.1016/j.scitotenv.2023.164951. Online ahead of print.ABSTRACTOxybenzone, an environmental pollutant affecting both agriculture and aquatic ecological integrity, has been demonstrated to act as a physiological and metabolic inhibitor on plants, animals, and microorganisms. Research on oxybenzone in higher plants has focused on the above-ground anatomy (leaves), while research on the under-ground parts (roots) has been neglected. In this study, the changes in plant root protein expression and metabolic pathways under oxybenzone treatment were explored through a combined proteomics and metabolomics analysis. A total of 506 differential proteins and 96 differential metabolites were identified, which were mainly distributed in critical pathways such as those for carbon (C) and nitrogen (N) metabolism, lipid metabolism, and antioxidation. Bioinformatics analysis shows that oxybenzone toxicity is predominantly reflected in alterations to root respiratory homeostasis and the manifestation of damaging reactive oxygen species (ROS) and membrane lipid peroxidation, changes to disease resistance-associated proteins, changes to normal C-flow distribution, and the inhibition of cell absorption and utilization of N sources. Plants respond to oxybenzone stress mainly by reconfiguring the mitochondrial electron-transport-chain to bypass oxidative-damage components; improving the efficiency of the antioxidant system to remove excessively accumulated ROS; promoting the detoxification of harmful membrane lipid peroxides; increasing osmotic adjustment substance (such as proline and raffinose) accumulation; adjusting C flow distribution to produce more nicotinamide adenine dinucleotide phosphate (NADPH) for the glutathione cycle; and accumulating free amino acids to increase plant stress tolerant. Our results are the first to map the changes in the physiological and metabolic regulatory network of higher plant roots under oxybenzone stress.PMID:37331386 | DOI:10.1016/j.scitotenv.2023.164951

Difference in acute and chronic stage ischemic stroke metabolic markers with controls

Sun, 18/06/2023 - 12:00
J Stroke Cerebrovasc Dis. 2023 Jun 16;32(8):107211. doi: 10.1016/j.jstrokecerebrovasdis.2023.107211. Online ahead of print.ABSTRACTBACKGROUND: Acute Ischemic Stroke (AIS), a major cause of disability, was previously associated with multiple metabolomic changes, but many findings were contradictory. Case-control and longitudinal study designs could have played a role in that. To clarify metabolomic changes, we performed a simultaneous comparison of ischemic stroke metabolome in acute, chronic stages of stroke and controls.METHODS: Through the nuclear magnetic resonance (NMR) platform, we evaluated 271 serum metabolites from a cohort of 297 AIS patients in acute and chronic stages and 159 controls. We used Sparse Partial Least Squares-Discriminant analysis (sPLS-DA) to evaluate group disparity; multivariate regression to compare metabolome in acute, chronic stages of stroke and controls; and mixed regression to compare metabolome acute and chronic stages of stroke. We applied false discovery rate (FDR) to our calculations.RESULTS: The sPLS-DA revealed separation of the metabolome in acute, chronic stages of stroke and controls. Regression analysis identified 38 altered metabolites. Ketones, branched-chain amino acids (BCAAs), energy, and inflammatory compounds were mostly elevated, while alanine and glutamine were decreased in the acute stage. These metabolites declined/increased in the chronic stage, often to the same levels as in controls. Levels of fatty acids, phosphatidylcholines, phosphoglycerides, and sphingomyelins did not change between acute and chronic stages, but were different comparing to controls.CONCLUSION: Our pilot study identified metabolites associated with acute stage of ischemic stroke and those that are altered in stroke patients comparing to controls regardless of stroke acuity. Future investigation in a larger independent cohort is needed to validate these findings.PMID:37331250 | DOI:10.1016/j.jstrokecerebrovasdis.2023.107211

Pseudotargeted metabolomics-based random forest model for tracking plant species from herbal products

Sun, 18/06/2023 - 12:00
Phytomedicine. 2023 Jun 8;118:154927. doi: 10.1016/j.phymed.2023.154927. Online ahead of print.ABSTRACTBACKGROUND: The "one-to-multiple" phenomenon is prevalent in medicinal herbs. Accurate species identification is critical to ensure the safety and efficacy of herbal products but is extremely challenging due to their complex matrices and diverse compositions.PURPOSE: This study aimed to identify the determinable chemicalome of herbs and develop a reasonable strategy to track their relevant species from herbal products.METHODS: Take Astragali Radix-the typical "one to multiple" herb, as a case. An in-house database-driven identification of the potentially bioactive chemicalome (saponins and flavonoids) in AR was performed. Furthermore, a pseudotargeted metabolomics method was first developed and validated to obtain high-quality semi-quantitative data. Then based on the data matrix, the random forest algorithm was trained to predict Astragali Radix species from commercial products.RESULTS: The pseudotargeted metabolomics method was first developed and validated to obtain high-quality semi-quantitative data (including 56 saponins and 49 flavonoids) from 26 batches of AR. Then the random forest algorithm was well-trained by importing the valid data matrix and showed high performance in predicting Astragalus species from ten commercial products.CONCLUSION: This strategy could learn species-special combination features for accurate herbal species tracing and could be expected to promote the traceability of herbal materials in herbal products, contributing to manufacturing standardization.PMID:37331178 | DOI:10.1016/j.phymed.2023.154927

Effects of heat stress on the chemical composition, oxidative stability, muscle metabolism, and meat quality of Nile tilapia (Oreochromis niloticus)

Sun, 18/06/2023 - 12:00
Food Chem. 2023 Jun 14;426:136590. doi: 10.1016/j.foodchem.2023.136590. Online ahead of print.ABSTRACTThe present study investigated the effects of chronic heat stress (HS) on the chemical composition, oxidative stability, muscle metabolism, and meat quality of Nile tilapia (Oreochromis niloticus). Compared with the control (26 °C), chronic HS (32 °C) lowered growth performance, the contents of whole-body lipid, muscle protein, and muscle lipid. Also, HS significantly increased the contents of reactive oxygen species (ROS) and decreased antioxidative status, causing a decline in meat quality, including increased lipid and protein oxidation, the centrifugal water loss, and cooking loss as well as decreased the fragmentation index and pH at 24 h, which may be attributed to induced apoptosis by excessive ROS in Nile tilapia meat. Moreover, metabolomic analysis showed HS lowered flavor and nutritional value by affecting amino acid, lipid, and nucleotide metabolism. These results reveal that HS adversely affects oxidative stability, meat quality, flavor, and nutrition, warranting its recognition and prevention.PMID:37331137 | DOI:10.1016/j.foodchem.2023.136590

Dimethyl itaconate induces long-term innate immune responses and confers protection against infection

Sun, 18/06/2023 - 12:00
Cell Rep. 2023 Jun 16;42(6):112658. doi: 10.1016/j.celrep.2023.112658. Online ahead of print.ABSTRACTItaconate is an immunomodulatory metabolite produced by immune cells under microbial stimulation and certain pro-inflammatory conditions and triggers antioxidant and anti-inflammatory responses. We show that dimethyl itaconate, a derivative of itaconate previously linked to suppression of inflammation and widely employed as an alternative to the endogenous metabolite, can induce long-term transcriptional, epigenomic, and metabolic changes, characteristic of trained immunity. Dimethyl itaconate alters glycolytic and mitochondrial energetic metabolism, ultimately leading to increased responsiveness to microbial ligand stimulation. Subsequently, mice treated with dimethyl itaconate present increased survival to infection with Staphylococcus aureus. Additionally, itaconate levels in human plasma correlate with enhanced ex vivo pro-inflammatory cytokine production. Collectively, these findings demonstrate that dimethyl itaconate displays short-term anti-inflammatory characteristics and the capacity to induce long-term trained immunity. This pro-and anti-inflammatory dichotomy of dimethyl itaconate is likely to induce complex immune responses and should be contemplated when considering itaconate derivatives in a therapeutic context.PMID:37330914 | DOI:10.1016/j.celrep.2023.112658

Integrative analysis of the effects of organic and conventional farming methods on peanut based on transcriptome and metabolomics

Sun, 18/06/2023 - 12:00
Food Res Int. 2023 Sep;171:113065. doi: 10.1016/j.foodres.2023.113065. Epub 2023 May 29.ABSTRACTTo elucidate the nutritional quality of peanut under different farming methods, we selected two cultivars, "jihua13" and "jihua4", to grow in organic and conventional environments, respectively. After harvest, we measured physiological parameters and differential metabolites. Metabolomics showed that most of the amino acids, carbohydrates, and secondary metabolites in organically grown jihua4 were downregulated, which was completely the opposite in jihua13. Fatty acids associated with heart disease and hypertension are reduced in organically grown peanuts. In particular, the highly statistically significant tryptophan betaine seems to be used as a reference to distinguish between organic and conventional cultivation. Mechanisms leading to differences in crop chemical composition are explained by transcriptome analysis. The results of the transcriptome analysis indicated that organic cultivation largely affects the synthesis of amino acids and carbohydrates in jihua13. Combined analysis of transcriptome and metabolomics found that variety jihua13 is more sensitive to farming methods and produces more unsaturated fatty acids than jihua4.PMID:37330858 | DOI:10.1016/j.foodres.2023.113065

Comprehensive metabolomic analysis of Mangifera indica leaves using UPLC-ESI-Q-TOF-MS<sup>E</sup> for cell differentiation: An in vitro and in vivo study

Sun, 18/06/2023 - 12:00
Food Res Int. 2023 Sep;171:112993. doi: 10.1016/j.foodres.2023.112993. Epub 2023 May 27.ABSTRACTThe comprehensive metabolic profiling was performed in the leaf extracts of Mangifera indica and assessed for their significant therapeutic application in tissue engineering and regenerative medicine in both in vitro and in vivo studies. About 147 compounds were identified in the ethyl acetate and methanol extracts of M. indica using MS/MS fragmentation analysis and the selected compounds were quantified using LC-QqQ-MS analysis. The in vitro cytotoxic activity showed that the M. indica extracts enhance the proliferation of mouse myoblast cells in concentration-dependent manner. As well, the extracts of M. indica induce the myotube formation by generating oxidative stress in the C2C12 cells was confirmed. The western blot analysis clearly showed that the M. indica induce myogenic differentiation by upregulating the myogenic marker proteins such as PI3K, Akt, mTOR, MyoG, and MyoD. The in vivo studies showed that the extracts expedites the acute wound repair by formation of crust, wound closure and improves the blood perfusion towards the wound area. Together, the leaves of M. indica can be used as excellent therapeutic agent for tissue repair and wound healing applications.PMID:37330843 | DOI:10.1016/j.foodres.2023.112993

Metabolome shifts triggered by chlorine sanitisation induce Escherichia coli on fresh produce into the viable but nonculturable state

Sun, 18/06/2023 - 12:00
Food Res Int. 2023 Sep;171:113084. doi: 10.1016/j.foodres.2023.113084. Epub 2023 Jun 4.ABSTRACTFacing the increasing occurrence of "big six" Escherichia coli outbreaks linked to fresh produce, chlorine-based sanitisers are widely used for fresh produce decontamination in recent years. However, latest finding that chlorine may induce E. coli cells into a viable not nonculturable (VBNC) state is bringing a new challenge to the fresh produce industry. VBNC cells are undetectable by the plate count test, and yet they retain pathogenicity and are more antibiotic-resistant than culturable cells. As a result, their eradication is critical to ensure the safety of fresh produce. Understanding VBNC cells at the metabolic level may provide a breakthrough for their eradication. Therefore, this study was carried out to collect the VBNC pathogenic E. coli (O26:H11, O121:H19, and O157:H7) cells from chlorine-treated pea sprouts and characterise them using NMR-based metabolomics. From the globally increased metabolite contents detected in the VBNC E. coli cells as compared to the culturable cells, mechanisms underlying E. coli's VBNC induction were elucidated. These include rendering the energy generation scheme to become more compatible with the lowered energy needs, disaggregating protein aggregates to release amino acids for osmoprotection and later resuscitation, as well as increasing cAMP content to downregulate RpoS. These identified metabolic characteristics can inspire future development of targeted measures for VBNC E. coli cell inhibition. Our methods can also be applied to other pathogens to help lower the risk of overall foodborne diseases.PMID:37330837 | DOI:10.1016/j.foodres.2023.113084

Application and prospect of metabolomics-related technologies in food inspection

Sun, 18/06/2023 - 12:00
Food Res Int. 2023 Sep;171:113071. doi: 10.1016/j.foodres.2023.113071. Epub 2023 Jun 5.ABSTRACTBACKGROUND: Food inspection covers a broad range of topics, including nutrient analysis, food pollutants, food auxiliary materials, additives, and food sensory identification. The foundation of diverse subjects like food science, nutrition, health research, and the food industry, as well as the desired reference for drafting trade and food legislation, makes food inspection highly significant. Because of their high efficiency, sensitivity, and accuracy, instrumental analysis methods have gradually replaced conventional analytical methods as the primary means of food hygiene inspection.SCOPE AND APPROACH: Metabolomics-based analysis technology, such as nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), and capillary electrophoresis-mass spectrometry (CE-MS), has become a widely used analytics platform. This research provides a bird's eye view of the application and future of metabolomics-related technologies in food inspection.KEY FINDINGS AND CONCLUSIONS: We have provided a summary of the features and the application range of various metabolomics techniques, the strengths and weaknesses of different metabolomics platforms, and their implementation in specific inspection procedures. These procedures encompass the identification of endogenous metabolites, the detection of exogenous toxins and food additives, analysis of metabolite alterations during processing and storage, as well as the recognition of food adulteration. Despite the widespread utilization and significant contributions of metabolomics-based food inspection technologies, numerous challenges persist as the food industry advances and technology continues to improve. Thus, we anticipate addressing these potential issues in the future.PMID:37330829 | DOI:10.1016/j.foodres.2023.113071

Integrated microbiomic and metabolomic analyses reveal the mechanisms by which bee pollen and royal jelly lipid extracts ameliorate colitis in mice

Sun, 18/06/2023 - 12:00
Food Res Int. 2023 Sep;171:113069. doi: 10.1016/j.foodres.2023.113069. Epub 2023 Jun 2.ABSTRACTBee pollen (BP) and royal jelly (RJ) have shown therapeutic effects against colitis, but the functional components contained therein remain elusive. Here, we used an integrated microbiomic-metabolomic strategy to clarify the mechanism by which bee pollen lipid extracts (BPL) and royal jelly lipid extracts (RJL) ameliorated dextran sulfate sodium (DSS)-induced colitis in mice. Lipidomic results showed that levels of ceramide (Cer), lysophosphatidylcholine (LPC), phosphatidylcholine (PC), and phosphatidylethanolamine (PE) were significantly higher in BPL than in RJL. The anti-inflammatory efficacy of BPL surpassed that of RJL, although both BPL and RJL could attenuate DSS-induced colitis through several mechanisms: reducing the disease activity index (DAI); decreasing histopathological damage; inhibiting the expression of genes encoding proinflammatory cytokines; improving intestinal microbial community structure, and modulating host metabolism. These findings demonstrated that BPL and RJL have great potential as functional ingredients for the production of dietary supplements to prevent early colitis.PMID:37330827 | DOI:10.1016/j.foodres.2023.113069

Widely targeted metabolomic analysis revealed the effects of alkaline stress on nonvolatile and volatile metabolites in broomcorn millet grains

Sun, 18/06/2023 - 12:00
Food Res Int. 2023 Sep;171:113066. doi: 10.1016/j.foodres.2023.113066. Epub 2023 Jun 2.ABSTRACTBroomcorn millet (BM) is a future smart food. However, no information is available on the metabolism of BM grains under alkaline stress. In this study, the effects of alkaline stress on nonvolatile and volatile metabolites in the BM grains of two varieties (S223 and T289) were investigated through metabolomics approaches. All 933 nonvolatile metabolites and 313 volatile metabolites were identified, with 114 and 89 nonvolatile metabolites and 16 and 20 volatile metabolites accumulating differentially under normal vs. alkaline stresses of S223 and T289, respectively. The results indicated that alkaline stress altered phenylpropanoids, flavonoids, flavone and flavonol, valine, leucine, and isoleucine biosynthesis, as well as arginine, proline, tryptophan, and ascorbate metabolism. The effects of alkaline stress were not identical between the two varieties, which could lead to variations in active substance content. These results provide valuable information for further studies on food chemistry and the functional food development of BM grains.PMID:37330826 | DOI:10.1016/j.foodres.2023.113066

Comparative antioxidant activity and untargeted metabolomic analyses of cherry extracts of two Chinese cherry species based on UPLC-QTOF/MS and machine learning algorithms

Sun, 18/06/2023 - 12:00
Food Res Int. 2023 Sep;171:113059. doi: 10.1016/j.foodres.2023.113059. Epub 2023 Jun 1.ABSTRACTP. pseudocerasus and P. tomentosa are the two native Chinese cherry species of high economic and ornamental worths. Little is known about the metabolic information of P. pseudocerasus and P. tomentosa. Effective means are lacking for distinguishing these two similar species. In this study, the differences in total phenolic content (TPC), total flavonoid content (TFC), and in vitro antioxidant activities in 21 batches of two species of cherries were compared. A comparative UPLC-QTOF/MS-based metabolomics coupled with three machine learning algorithms was established for differentiating the cherry species. The results demonstrated that P. tomentosa had higher TPC and TFC with average content differences of 12.07 times and 39.30 times, respectively, and depicted better antioxidant activity. Total of 104 differential compounds were identified by UPLC-QTOF/MS metabolomics. The major differential compounds were flavonoids, organooxygen compounds, and cinnamic acids and derivatives. Correlation analysis revealed differences in flavonoids content such as procyanidin B1 or isomer and (Epi)catechin. They could be responsible for differences in antioxidant activities between the two species. Among three machine learning algorithms, the prediction accuracy of support vector machine (SVM) was 85.7%, and those of random forest (RF) and back propagation neural network (BPNN) were 100%. BPNN exhibited better classification performance and higher prediction rate for all testing set samples than those of RF. The study herein found that P. tomentosa had higher nutritional value and biological functions, and thus considered for usage in health products. Machine models based on untargeted metabolomics can be effective tools for distinguishing these two species.PMID:37330825 | DOI:10.1016/j.foodres.2023.113059

Integrated microbiology and metabolomics analysis reveal responses of cotton rhizosphere microbiome and metabolite spectrum to conventional seed coating agents

Sat, 17/06/2023 - 12:00
Environ Pollut. 2023 Jun 15:122058. doi: 10.1016/j.envpol.2023.122058. Online ahead of print.ABSTRACTFludioxonil (FL) and metalaxyl-M·fludioxonil·azoxystrobin (MFA) are conventional seed coating agents for controlling cotton seedling diseases. However, their effects on seed endophytic and rhizosphere microecology are still poorly understood. This study aimed to assess the effects of FL and MFA on cotton seed endophytes, rhizosphere soil enzymatic activities, microbiome and metabolites. Both seed coating agents significantly changed seed endophytic bacterial and fungal communities. Growing coated seeds in the soils originating from the Alar (AL) and Shihezi (SH) region inhibited soil catalase activity and decreased both bacterial and fungal biomass. Seed coating agents increased rhizosphere bacterial alpha diversity for the first 21 days but decreased fungal alpha diversity after day 21 in the AL soil. Seed coating reduced the abundance of a number of beneficial microorganisms but enriched some potential pollutant-degrading microorganisms. Seed coating agents may have affected the complexity of the co-occurrence network of the microbiome in the AL soil, reducing connectivity, opposite to what was observed in the SH soil. MFA had more pronounced effects on soil metabolic activities than FL. Furthermore, there were strong links between soil microbial communities, metabolites and enzymatic activities. These findings provide valuable information for future research and development on application of seed coatings for disease management.PMID:37330187 | DOI:10.1016/j.envpol.2023.122058

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