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

Multi-tissue transcriptomic and serum metabolomic assessment reveals systemic implications of acute ozone-induced stress response in male Wistar Kyoto rats

Sun, 10/09/2023 - 12:00
Metabolomics. 2023 Sep 10;19(9):81. doi: 10.1007/s11306-023-02043-5.ABSTRACTAir pollutant exposures have been linked to systemic disease; however, the underlying mechanisms between responses of the target tissue and systemic effects are poorly understood. A prototypic inducer of stress, ozone causes respiratory and systemic multiorgan effects through activation of a neuroendocrine stress response. The goal of this study was to assess transcriptomic signatures of multiple tissues and serum metabolomics to understand how neuroendocrine and adrenal-derived stress hormones contribute to multiorgan health outcomes. Male Wistar Kyoto rats (12-13 weeks old) were exposed to filtered air or 0.8 ppm ozone for 4-hours, and blood/tissues were collected immediately post-exposure. Each tissue had distinct expression profiles at baseline. Ozone changed 1,640 genes in lung, 274 in hypothalamus, 2,516 in adrenals, 1,333 in liver, 1,242 in adipose, and 5,102 in muscle (adjusted p-value < 0.1, absolute fold-change > 50%). Serum metabolomic analysis identified 863 metabolites, of which 447 were significantly altered in ozone-exposed rats (adjusted p-value < 0.1, absolute fold change > 20%). A total of 6 genes were differentially expressed in all 6 tissues. Glucocorticoid signaling, hypoxia, and GPCR signaling were commonly changed, but ozone induced tissue-specific changes in oxidative stress, immune processes, and metabolic pathways. Genes upregulated by TNF-mediated NFkB signaling were differentially expressed in all ozone-exposed tissues, but those defining inflammatory response were tissue-specific. Upstream predictor analysis identified common mediators of effects including glucocorticoids, although the specific genes responsible for these predictors varied by tissue. Metabolomic analysis showed major changes in lipids, amino acids, and metabolites linked to the gut microbiome, concordant with transcriptional changes identified through pathway analysis within liver, muscle, and adipose tissues. The distribution of receptors and transcriptional mechanisms underlying the ozone-induced stress response are tissue-specific and involve induction of unique gene networks and metabolic phenotypes, but the shared initiating triggers converge into shared pathway-level responses. This multi-tissue transcriptomic analysis, combined with circulating metabolomic assessment, allows characterization of the systemic inhaled pollutant-induced stress response.PMID:37690105 | DOI:10.1007/s11306-023-02043-5

Characterization of chemoresistant human non-small cell lung cancer cells by metabolic and lipidomic profiling

Sun, 10/09/2023 - 12:00
Metabolomics. 2023 Sep 10;19(9):80. doi: 10.1007/s11306-023-02045-3.ABSTRACTINTRODUCTION: Lung cancer is one of the most malignant cancers and the leading cause of cancer-related deaths worldwide, while acquired chemoresistance would represent a major problem in the treatment of non-small cell lung cancer (NSCLC) because of the reduced treatment effect and increased rates of recurrence.METHODS: To establish the chemoresistant NSCLC cells, doxorubicin was treated to A549 cells over 3 months at gradually increasing concentrations from 0.03 to 0.5 µM. Real-time PCR and Western blotting were employed for investigating mRNA and protein expression of the glutathione peroxidase (GPX) protein family and multidrug resistance protein 1 (MRP1) in A549 and A549/CR cells. We also employed gas chromatography mass-spectrometry and nano electrospray ionization mass-spectrometry coupled with multivariate statistical analysis to characterize the unique metabolic and lipidomic profiles of chemoresistant NSCLC cells in order to identify potential therapeutic targets.RESULTS: Reactive oxygen species levels were decreased, and mRNA and protein levels of GPX2 and multidrug resistance protein 1 (MRP1) were increased in A549/CR. We identified 87 metabolites and intact lipid species in A549 and A549/CR. Among these metabolites, lactic acid, glutamic acid, glycine, proline, aspartic acid, succinic acid, and ceramide, alongside the PC to PE ratio, and arachidonic acid-containing phospholipids were suggested as characteristic features of chemoresistant NSCLC cells (A549/CR).CONCLUSIONS: This study reveals characteristic feature differences between drug-resistance NSCLC cells and their parental cells. We suggest potential therapeutic targets in chemoresistant NSCLC. Our results provide new insight into metabolic and lipidomic alterations in chemoresistant NSCLC. This could be used as fundamental information to develop therapeutic strategies for the treatment of chemoresistant NSCLC patients.PMID:37690093 | DOI:10.1007/s11306-023-02045-3

Chemical markers of a rare honey from the traditional spice plant Amomum tsao-ko Crevost et Lemarié, via integrated GC-MS and LC-MS approaches

Sun, 10/09/2023 - 12:00
Food Res Int. 2023 Oct;172:113234. doi: 10.1016/j.foodres.2023.113234. Epub 2023 Jul 5.ABSTRACTThe precious medicinal plant, Amomum tsao-ko Crevost et Lemarié, is the nectariferous plant from which the rare Amomum tsao-ko Crevost et Lemarié honey (ATH) is produced. Presently, chemical markers for authentication of this honey are not available due to the lack of data on its chemical composition. Here, we analyzed the volatile components and their odor activity values (OAVs), which revealed that the unique aroma was mildly flowery and fruity, accompanied by subtle sweet and fresh undertones. Since non-volatile chemicals are more reliable markers for routine authentication, we used a metabolomic approach combined with NMR-based identification to find and confirm a suitable compound to unambiguously distinguish ATH from other honeys. Isorhamnetin 3-O-neohesperidoside ranged from 3.62 to 9.38 mg/kg in ATH and was absent in the other tested honeys. In sum, the study uncovered unique chemical characteristics of ATH that will be helpful to control its quality.PMID:37689964 | DOI:10.1016/j.foodres.2023.113234

Identification of nonvolatile chemical constituents in Chinese Huangjiu using widely targeted metabolomics

Sun, 10/09/2023 - 12:00
Food Res Int. 2023 Oct;172:113226. doi: 10.1016/j.foodres.2023.113226. Epub 2023 Jul 4.ABSTRACTHuangjiu is a traditional Chinese alcoholic beverage, whose non-volatile chemical profile remains unclarified. Here, the non-volatile compounds of Huangjiu were first identified using a widely targeted metabolomics analysis. In total, 1146 compounds were identified, 997 of them were identified in Huangjiu for the first time. Moreover, 113 compounds were identified as key active ingredients of traditional Chinese medicines and 78 components were found as active pharmaceutical ingredients against 389 diseases. In addition, the comparative analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that Huangjiu from different regions differ in metabolite composition. Cofactor and amino acid biosynthesis and ABC transport were the dominant metabolic pathways. Furthermore, 7 metabolic pathways and 77 metabolic pathway regulatory markers were further found to be related with the different characteristics of different Huangjius. This study provides a theoretical and material basis for the quality control, health efficacy, and industrial development of Huangjiu.PMID:37689963 | DOI:10.1016/j.foodres.2023.113226

Metagenomics and metabolomics of Toddy, an Indian fermented date palm beverage

Sun, 10/09/2023 - 12:00
Food Res Int. 2023 Oct;172:113205. doi: 10.1016/j.foodres.2023.113205. Epub 2023 Jun 29.ABSTRACTToddy is a popular fermented palm beverage of India. No scientific information on shotgun metagenomics and metabolomics are available on toddy of India till date. Hence, we choose the fermented date palm beverage, locally called khejur toddy, of West Bengal and Jharkhand states of India, to profile microbial community, their targeted and untargeted metabolites to study the putative bio-functional genes corresponding to regulatory metabolic pathways. Shotgun-based metataxonomic analyses revealed the existence of all domains where bacteria were the most abundant domain (94.48%) followed by eukaryotes (3.38%), viruses (1.53%) and archaea (0.61%). Overall, 54 phyla, 363 families, 1087 genera and 1885 species were observed and identified. Bacillota (49.3%) was the most abundant bacterial phylum. At species level, several species of bacteria and yeasts were detected in toddy samples which included Leuconostoc mesenteroides,Leuconostoc citreum,Lactobacillus helveticus,Lactiplantibacillus plantarum,Lactococcus lactis, Acetobacter malorum, Gluconobacter japonicus, Gluconacetobacter liquefaciens, Fructobacillus durionis, Zymomonas mobilis and yeastsSaccharomyces cerevisiae, Hanseniaspora uvarumandHanseniaspora guilliermondii. Toddy metagenome was also compared with metagenome of pulque, the Mexican fermented fresh sap ofAgave, which was retrieved from NCBI database, and also with metagenomic data of some amplicon-based previous studies on toddy and African fermented palm drink for similarity, dissimilarity and uniqueness among them. Predictive biosynthesis of ethanol, acetic acid, butanoate, linalool, staurosporine, prodigiosin, folic acid, riboflavin, etc. were annotated by KEGG/COG database. Clustered regularly interspaced short palindromic repeats (CRISPR) analysis detected 23 arrays (average length 23.69 bp ± 4.28). Comprehensive Antibiotic Resistance Database (CARD) analysis did not show the presence of any momentous antibiotic resistance gene among the major microbial members. Metabolomics analysis detected many primary and secondary metabolites. We believe this is the first report on complete shotgun metagenomics, and metabolomics of fermented palm drink of India as well as Eastern India.PMID:37689952 | DOI:10.1016/j.foodres.2023.113205

A comprehensive analytical framework integrating liquid chromatography-tandem mass spectrometry metabolomics with chemometrics for metabolite profiling of lettuce varieties and discovery of antibacterial agents

Sun, 10/09/2023 - 12:00
Food Res Int. 2023 Oct;172:113178. doi: 10.1016/j.foodres.2023.113178. Epub 2023 Jun 20.ABSTRACTThis study comprehensively characterized the metabolite profiles of six lettuce varieties and established the correlation between the elucidated profiles and their antivirulence effects. A total of 195 metabolites were annotated using LC-QTOF-MS/MS metabolomics assisted by molecular networking and integrated with chemometrics. Red varieties (red longifolia and lolla rosa) demonstrated higher chlorogenic and chicoric acids suggesting their antioxidant properties. In parallel, amino acids and disaccharides were enriched in romaine longifolia rationalizing its palatable taste and nutritional potential, while crispa, capitata, and lolla bionda presented a high β-carboline alkaloid content. The antibacterial and antihemolytic potential of all varieties against methicillin-sensitive and methicillin-resistant Staphylococcus aureus was assessed and validated by prominent downregulation of α-hemolysin transcriptional levels in both strains. Moreover, correlation analysis revealed sesquiterpenes, β-carboline alkaloids, amino acids, and oxy-fatty acids as the main bioactives. Results emphasize lettuce significance as a functional food and nutraceutical source, and highlight varieties naturally rich in antibacterial agents to adapt breeding programs.PMID:37689928 | DOI:10.1016/j.foodres.2023.113178

Comparative characterization of flavor precursors and volatiles of Taihe black-boned silky fowl and Hy-line Brown yolks using multiomics and GC-O-MS-based volatilomics

Sun, 10/09/2023 - 12:00
Food Res Int. 2023 Oct;172:113168. doi: 10.1016/j.foodres.2023.113168. Epub 2023 Jun 18.ABSTRACTEggs are nutritious and highly valued by consumers. However, egg flavor varies greatly among different hen breeds. The present study used gas chromatography-olfactometry-mass spectrometry-based volatilomics to identify and compare volatile compounds in Taihe black-boned silky fowl (TS) and Hy-line Brown (HL) egg yolks. In addition, the relationships between the levels of different metabolites and lipids and flavor-associated differences were investigated using multiomics. Twenty-eight odorants in total were identified; among them, the levels of 3-methyl-butanal, 1-octen-3-ol, 2-pentylfuran, and (E, E)-2,4-decadienal differed significantly (P < 0.05) between TS and HL egg yolks. The difference in flavor compounds results in TS egg yolks having a stronger overall odor and flavor and a higher acceptance level than HL egg yolks. Metabolomic analysis revealed that 112 metabolites in the egg yolks were significantly different between the two breeds. Furthermore, these different metabolites in the egg yolks of both breeds were significantly enriched in phenylalanine, tyrosine, and tryptophan biosynthesis pathways and phenylalanine metabolism, alanine, aspartate, and glutamate metabolism pathways (P < 0.05), as identified by both metabolite set enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Lipidomic analysis revealed significant differences in the lipid subclasses, lipid molecules, and fatty acid profiles between the egg yolks from the two breeds. As a result, 48 lipid molecules had variable influence in projection values > 1 based on the partial least squares regression model, which may play a role in the differences in aroma characteristics between the two breeds through oxidative degradation of fatty acids. Our study revealed the metabolite, lipid, and volatility profiles of TS and HL egg yolks and may provide an important basis for improving egg flavor to satisfy various consumer preferences.PMID:37689921 | DOI:10.1016/j.foodres.2023.113168

Metabolomics investigation of global responses of Cronobacter sakazakii against common sanitizing in infant formula processing environments

Sun, 10/09/2023 - 12:00
Food Res Int. 2023 Oct;172:113162. doi: 10.1016/j.foodres.2023.113162. Epub 2023 Jun 19.ABSTRACTCronobacter sakazakii, an opportunistic bacterium, has raised a serious outbreak in powdered infant formula recent years. In this work, four sanitizing strategies used during infant formula processing, including chlorine, quaternary ammonium chloride (QAC), 60 °C heating, and malic acid (MA), were utilized against C. sakazakii among planktonic, air-dried (A), and air-dried & washed (AW) state, followed by an exploration of the metabolic responses induced by these treatments via a dual-platform metabolomics analysis with the ultra-high performance liquid chromatography-mass spectrometry and nuclear magnetic resonance. In the planktonic state, MA was the most effective in inhibiting bacterial growth, followed by chlorine, QAC, and 60 °C heating. Under A state, the efficacy of heating improved considerably, compared to that in the planktonic state, and remained unaltered under AW state. Chlorine and QAC were ineffective to control bacterial growth under A state, but their efficacy rose under AW state. Furthermore, the metabolomic analysis revealed chlorine induces amino acids catabolism, membrane lysis, and depression in carbohydrate and nucleotide metabolism in both planktonic and AW states, while the initiation of antioxidation mechanism was only found under AW state. Although the metabolic change caused by QAC in the planktonic state was similar to chlorine, the accumulation of osmoprotectant and membrane phospholipids within the AW cells reflected the effort to restore intracellular homeostasis upon QAC. Heating was characterized by considerable amino acid anabolism, along with mildly perturbed carbohydrate and nucleotide metabolism for heat shock protein preparation in both states. Lastly, MA promoted amino acid-dependent acid resistance under the planktonic state, and the regulation of antioxidation and osmoprotection under AW state. The metabolomics study elucidated the intracellular perturbation induced by common sanitizing, as well as the bacterial response, which provides insights for novel sanitization development.PMID:37689917 | DOI:10.1016/j.foodres.2023.113162

Integrated volatile compounds and non-targeted metabolomics analysis reveal the characteristic flavor formation of proteins in grouper (Epinephelus coioides) during cold storage

Sun, 10/09/2023 - 12:00
Food Res Int. 2023 Oct;172:113145. doi: 10.1016/j.foodres.2023.113145. Epub 2023 Jun 15.ABSTRACTMicroorganisms, lipids, and proteins always interact in a complex way in the fish matrix, which becomes a hindrance to evaluate the quality of the individual factors affecting them. In order to investigate the relationship between protein deterioration and volatile compounds (VOCs) in grouper during cold storage, the myofibril protein (MP) was used as a single-factor study to exclude microorganisms and lipids effects. The oxidation and degradation of MP during storage at 4 ℃ were evaluated, including MP content, total sulfhydryl content, carbonyl content, spatial structure and microstructure. Headspace-solid phase microextraction- gas chromatography-mass spectrometry (HS-SPME-GC-MS) was used to analyze the VOCs of grouper MP, and a total of 7 key VOCs were selected, including three ketones (2-nonanone, 2-undecanone and 2-tridecanone), three esters (methyl butyrate, methyl palmitate and methyl ester 9-octadecenoic acid) and one alcohol (3-methyl-1-butanol). At the same time, a non-targeted metabolomics method based on UPLC-Q-Extractive Orbitrap was used to investigate the changes in metabolites during MP storage. A total of 107 up-regulated differential metabolites and 7 down-regulated metabolites were annotated, and 6 metabolic pathways highly related to proteins were screened. Spearman correlation analysis showed that 7 key VOCs are associated with the biosynthesis and metabolism of ornithine and lysine. And a possible solution to protein deterioration in grouper was proposed, which provided a reference for improving protein quality and regulating flavor formation during cold storage of grouper at source.PMID:37689909 | DOI:10.1016/j.foodres.2023.113145

The formation mechanism of aroma quality of green and yellow teas based on GC-MS/MS metabolomics

Sun, 10/09/2023 - 12:00
Food Res Int. 2023 Oct;172:113137. doi: 10.1016/j.foodres.2023.113137. Epub 2023 Jun 15.ABSTRACTAroma is a crucial determinant of tea quality. While some studies have examined the aroma of yellow tea, there are no reports of the difference and formation mechanism of aroma quality between yellow and green teas from the same tea tree variety. This study employed gas chromatography-mass spectrometry to investigate the difference and formation mechanism of the aroma of yellow and green tea at the omics level, based on sensory evaluation. The sensory evaluation revealed that green tea has a distinct faint scent and bean aroma, while yellow tea, which was yellowed for 48 h, has a noticeable corn aroma and sweet fragrance. A total of 79 volatile metabolites were detected in the processing of yellow and green tea, covering 11 subclasses and 27 were differential volatile metabolites. Benzoic acid, 2-(methylamino-), methyl ester, terpinen-4-ol ethanone, 1-(1H-pyrrol-2-yl-), 3-penten-2-one, 4-methyl- and benzaldehyde were characteristic components of the difference in aroma quality between green and yellow teas. Eleven volatile metabolites significantly contributed to the aroma quality of green and yellow teas, especially acetic acid, 2-phenylethyl ester, with rose and fruity aromas. KEGG enrichment analysis showed that the arginine and proline metabolism might be the key mechanism of aroma formation during green and yellow teas' processing. These finding provide a theoretical basis way for the aroma formation of green and yellow teas.PMID:37689901 | DOI:10.1016/j.foodres.2023.113137

Metabolite profiling identifies chemical markers associated with the cytotoxic properties of roasted fermented avocado seeds

Sun, 10/09/2023 - 12:00
Food Res Int. 2023 Oct;172:113131. doi: 10.1016/j.foodres.2023.113131. Epub 2023 Jun 25.ABSTRACTStudies have demonstrated avocado seeds are a good source of bioactive compounds. This study investigated the effects of roasting on the metabolites and anticancer activities of fermented avocado seeds. All three anti-cancer activities of fermented avocado seeds were higher at lower roasting temperature and time. The best inhibition effect was found against Hep G2 followed by the MDA-MB-231 and MCF-7 cancer cell lines. Untargeted metabolite profiling using gas chromatography-mass spectrometry resulted in identification of 208 metabolites. In total, 41 metabolites identified had VIP values more than 1 using PLS-R that were related to anticancer activities. All amino acids and most sugars were higher at lower roasting temperature and positively correlated to anticancer activity. The roasting conditions for optimal antioxidant and anticancer activities were determined to be 121 °C for 9 min. Findings showed that fermented avocado seed powder has the potential to become a functional food ingredient with beneficial bioctive properties.PMID:37689896 | DOI:10.1016/j.foodres.2023.113131

Omics approaches to investigate the neuroprotective capacity of a Citrus sinensis (sweet orange) extract in a Caenorhabditis elegans Alzheimer's model

Sun, 10/09/2023 - 12:00
Food Res Int. 2023 Oct;172:113128. doi: 10.1016/j.foodres.2023.113128. Epub 2023 Jun 12.ABSTRACTCitrus sinensis by-products are a promising source of neuroprotective molecules. In this study, a pressurized liquid extract of Citrus by-products (PLE100) has been extensively characterized, and its neuroprotective capacity tested in the Caenorhabditis elegans strain CL4176, a validated in vivo model of Alzheimer's disease (AD). More than 450 compounds have been annotated in the extract, being triacylglycerols (TGs), stigmastanes, fatty acids (FAs) and carbohydrates the most abundant. The results demonstrate that worms PLE100-treated are significantly protected in a dose-dependent manner against the Aβ-peptide paralysis toxicity. The RNA-Seq data showed an alteration of 294 genes mainly related to the stress response defense along with genes involved in the lipid transport and metabolism. Moreover, the comprehensive metabolomics study allowed the identification of 818 intracellular metabolites, of which 54 were significantly altered (mainly lipids). The integration of these and previous results provides with new evidences of the protection mechanisms of this promising extract.PMID:37689893 | DOI:10.1016/j.foodres.2023.113128

Oat bran prevents high-fat-diet induced muscular dysfunction, systemic inflammation and oxidative stress through reconstructing gut microbiome and circulating metabolome

Sun, 10/09/2023 - 12:00
Food Res Int. 2023 Oct;172:113127. doi: 10.1016/j.foodres.2023.113127. Epub 2023 Jun 12.ABSTRACTWestern-type diet characterized by high fat emerges a promoter of skeletal muscle dysfunctions. Oat bran was typically considered a healthy food of premium quality for its abundant dietary fiber. The present study comprehensively explored the effects of a diet rich in oat bran on skeletal muscle disfunctions in high-fat diet (HFD) fed mice. Dietary-fiber-rich oat bran significantly ameliorated HFD-induced skeletal muscle function abnormalities, as evidenced by a phenotype improvement in mice grip strength and endurance treadmill running distance, accompanied with the regulation of muscle functions related gene expressions, namely Fis1, Cytc, Mhy2 and Mhy4. Oat bran suppressed the production of systemic inflammatory cytokines while promoted superoxide dismutase and glutathione. Furthermore, oat bran significantly impacted gut microbiota composition by promoting short chain fatty acids (SCFAs) producers and certain probiotic genera, along with the enhancement of SCFAs. Oat bran also significantly decreased the circulating levels of inflammation-related metabolites and played roles in MAPK signaling, thereafter influencing skeletal muscle functions. Collectively, benefits from integration of biomedical indicators, microbiomics, and metabolomics demonstrates the benefits of oat bran consumption on prevention of HFD-related muscular dysfunctions via alleviating HFD-induced inflammation, gut dysbiosis, and systemic metabolism, pinpointing a novel mechanism underlying the muscle-promoting property of oat bran.PMID:37689892 | DOI:10.1016/j.foodres.2023.113127

Exploring the roles of microorganisms and metabolites in the 30-year aging process of the dried pericarps of Citrus reticulata 'Chachi' based on high-throughput sequencing and comparative metabolomics

Sun, 10/09/2023 - 12:00
Food Res Int. 2023 Oct;172:113117. doi: 10.1016/j.foodres.2023.113117. Epub 2023 Jun 12.ABSTRACTGuangChenpi (GCP), the dried pericarps of Citrus reticulata 'Chachi', has been consumed daily as a food and dietary supplement in China for centuries. Its health benefits are generally recognized to be dependent on storage time. However, the specific roles of microorganisms and metabolites during long-term storage are still unclear. In this study, comparative metabolomics and high-throughput sequencing techniques were used to investigate the effects of co-existing microorganisms on the metabolites in GCP stored from 1 to 30 years. In total, 386 metabolites were identified and characterized. Most compounds were flavonoids (37%), followed by phenolic acids (20%). Seventeen differentially upregulated metabolites were identified as potential key metabolites in GCP, and 8 of them were screened out as key active ingredients by Venn diagram comparative analyses and verified by network pharmacology and molecular docking. In addition, long-term storage could promote the accumulation of secondary metabolites. Regarding the GCP microbiota, Xeromyces dominated the whole 30-year aging process.Moreover, Spearman correlation analysis indicated that Bacillus thuringiensis and Xeromyces bisporus, the dominant bacterial and fungal species, were strongly associated with the key active metabolites. Our results suggested that the change of active ingredients caused by the dominant microbial is one of the mechanisms affecting the GCP aging process. Our study provides novel functional insights and research perspectives on microorganism-associated metabolite changes that may improve the GCP aging process.PMID:37689884 | DOI:10.1016/j.foodres.2023.113117

Metabolomic and transcriptomic analyses reveal comparisons against liquid-state fermentation of primary dark tea, green tea and white tea by Aspergillus cristatus

Sun, 10/09/2023 - 12:00
Food Res Int. 2023 Oct;172:113115. doi: 10.1016/j.foodres.2023.113115. Epub 2023 Jun 15.ABSTRACTLiquid-state fermentation (LSF) of tea leaves is a promising way to obtain tea-based nutraceutical products rich in various bioactive compounds. In the study, the changes of bioactive compounds, tea pigments and complex metabolites from LSF of primary dark tea, green tea and white tea infusions with Aspergillus cristatus were determined. Chemical analyses revealed that soluble sugars, monosaccharide composition, total polyphenols, total flavonoids, free amino acids, soluble proteins and tea pigments were changed in different ways. An untargeted metabolomic analysis and ribonucleic acid sequencing (RNA-seq) based transcriptomic analysis were performed to investigate the metabolic differentiation and clarify the key differentially expressed genes (DEGs, fold change >2 and p < 0.05), showing that amino acid metabolism, carbohydrate metabolism and lipid metabolism were the most enriched pathways during A. cristatus fermentation of primary dark tea, green tea and white tea infusions. In addition, glycerophospholipid metabolism, linoleic acid metabolism and phenylalanine metabolism were greatly accumulated in the fermentation of primary dark tea and white tea infusions; Pyruvate metabolism, glycolysis/gluconeogenesis, fatty acid degradation, tyrosine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis and valine and leucine, isoleucine degradation were greatly accumulated in the fermentation of primary dark tea and green tea infusions; Starch and sucrose metabolism was greatly accumulated in the fermentation of green tea and white tea infusions; Galactose metabolism was significantly enhanced in the fermentation of primary dark tea infusion; Amino sugar and nucleotide sugar metabolism, sphingolipid metabolism and alanine, aspartate and glutamate metabolism were significantly enhanced in the fermentation of green tea infusion. Besides, some other pathways involving aminobenzoate degradation, biosynthesis of cofactors, pyrimidine metabolism, benzoxazinoid biosynthesis and phenazine biosynthesis, tropane, piperidine and pyridine alkaloid biosynthesis and flavone and flavonol biosynthesis also differed from each other. These findings support that A. cristatus plays a vital role in the biochemical and genetic regulation of metabolite profile, and could be considered a potential prospect for better use of A. cristatus on different kinds of tea materials.PMID:37689883 | DOI:10.1016/j.foodres.2023.113115

Widely targeted metabolomics reveal the glucosinolate profile and odor-active compounds in flowering Chinese cabbage powder

Sun, 10/09/2023 - 12:00
Food Res Int. 2023 Oct;172:113121. doi: 10.1016/j.foodres.2023.113121. Epub 2023 Jun 12.ABSTRACTWidely targeted metabolomics were performed to explore the differences in glucosinolate and odor-active compound levels between flowering Chinese cabbage powder (FCCP) under vacuum-drying and oven-drying conditions. Twenty-three aliphatic, five indole, and three aromatic glucosinolates were identified in two pretreated FCCP. Higher aliphatic glucosinolate levels were retained in vacuum-dried cabbage powder compared to oven-dried samples, and they were negatively correlated with treated temperatures. A total of 36 major odor contributing compounds were detected, including 5 sulfur compounds, 10 aldehydes, 9 heterocyclic compounds, 7 nitriles, 3 acids, and 2 others. 5-Hexenenitrile and (methyldisulfanyl)methan, provide typical pungent, sulfous, and vegetable notes in FCCP. Four major GSLs, namely 2(R)-hydroxy-3-butenyl glucosinolate, (2S)-2-hydroxy-4-pentenyl glucosinolate, 5-(methylthio)pentyl glucosinolate and 2-phenylethyl glucosinolate were the key precursors to form odor-active compounds. Higher temperatures in thermal effects promotes the formation of sulfur-containing and nitrile compounds compared to the vacuum-dried ones. This work can provide a guide for flavor and nutrition retention in FCCP process.PMID:37689882 | DOI:10.1016/j.foodres.2023.113121

Exploring major variable factors influencing flavor and microbial characteristics of upper jiupei

Sun, 10/09/2023 - 12:00
Food Res Int. 2023 Oct;172:113057. doi: 10.1016/j.foodres.2023.113057. Epub 2023 May 27.ABSTRACTThe flavor quality of jiupei gradually decreased with the increase of cellar height. In this study, high-throughput sequencing, metabolomics and HS-SPME-GC-MS techniques were used to explore the mechanism of flavor quality decline in upper jiupei in mud sealed cellars. The results showed the total content of flavor compounds increased from 1947.48 mg/L in top-site to 3855.51 mg/L in bottom of the cellar, and 19 differential flavor compounds were identified based on OPLS-DA, mainly including 12 esters such as ethyl hexanoate, ethyl butyrate, propyl hexanoate, hexyl caproate and 5 other substances such as caprylic acid, decanal and nonaldehyde. Lactobacillus, Prevotella and Methanobacterium were dominant genus of bacteria in all of cellars, while Thermomyces, Aspergillus, Pichia, Trichosporon and Rhizopus were the dominant genera of fungi. Oxygen was the key factor causing the quality heterogeneity of flavor substances and microbial communities in jiupei at different depths. Anaerobic micro-pressure sealed cellars (AMSC) method was developed and applied to jiupei fermentation, the difference in oxygen content between top site (5.90 ± 0.62 %) and bottom of the cellar (4.17 ± 0.75 %) in AMSC was smaller than that in mud sealed cellars, there were no significant differences in flavor substances content between top site and bottom of the cellar, and microbial communities showed no significant differences of the four-layer jiupei. This study provides a theoretical support for improving the flavor quality of upper jiupei.PMID:37689852 | DOI:10.1016/j.foodres.2023.113057

Study on the material basis and mechanism of Hemerocallis citrina Baroni on sleep-improvement using Drosophila activity monitoring, metabolomic, targeted screening and transcriptomic

Sun, 10/09/2023 - 12:00
Food Res Int. 2023 Oct;172:112562. doi: 10.1016/j.foodres.2023.112562. Epub 2023 Feb 6.ABSTRACTDaylily (Hemerocallis citrina Baroni, HC) is an edible plant and is traditionally considered with potential to improve sleep. Herein, based on the Drosophila activity monitoring, metabolome, targeted screening and transcriptome, the material basis and mechanism of HC on sleep-improvement was investigated. The results showed that the aqueous extracts of HC (HAE) as well as the ethanol extracts (HEE) all prolonged the total sleep time of insomnia fruit flies, especially HEE-60 and HEE-95 exhibited more significant effects. In addition, 539 of 728 found metabolites were screened as potential sleep-improved metabolites, and quercetin, linoleic acid, phenethyl caffeate, L-methionine and γ-aminobutyric acid were considered as core active metabolites. Meanwhile, 368 differentially expressed genes (DEGs) were revealed by transcriptomics analysis, and the neuroactive ligand-receptor interaction was deduced as the main pathway by KEGG pathway enrichment. Furthermore, nine DEGs located in this pathway, namely betaTry, deltaTry, gammaTry, epsilonTry, etaTry, iotaTry, lambdaTry, kappaTry and CG30031 were proven being up-regulated. All these results contribute to the development of HC-related functional foods.PMID:37689837 | DOI:10.1016/j.foodres.2023.112562

Metabolomics and transcriptomics based multi-omics integration reveals radiation-induced altered pathway networking and underlying mechanism

Sat, 09/09/2023 - 12:00
NPJ Syst Biol Appl. 2023 Sep 9;9(1):42. doi: 10.1038/s41540-023-00305-5.ABSTRACTRecent advancement in integrated multi-omics has significantly contributed to many areas of the biomedical field. Radiation research has also grasped uprising omics technologies in biomarker identification to aid in triage management. Herein, we have used a combinatorial multi-omics approach based on transcriptomics together with metabolomics and lipidomics of blood from murine exposed to 1 Gy (LD) and 7.5 Gy (HD) of total-body irradiation (TBI) for a comprehensive understanding of biological processes through integrated pathways and networking. Both omics displayed demarcation of HD group from controls using multivariate analysis. Dysregulated amino acids, various PC, PE and carnitine were observed along with many dysregulated genes (Nos2, Hmgcs2, Oxct2a, etc.). Joint-Pathway Analysis and STITCH interaction showed radiation exposure resulted in changes in amino acid, carbohydrate, lipid, nucleotide, and fatty acid metabolism. Elicited immune response was also observed by Gene Ontology. BioPAN has predicted Elovl5, Elovl6 and Fads2 for fatty acid pathways, only in HD group. Collectively, the combined omics approach facilitated a better understanding of processes uncovering metabolic pathways. Presumably, this is the first in radiation metabolomics that utilized an integrated omics approach following TBI in mice. Our work showed that omics integration could be a valuable tool for better comprehending the mechanism as well as molecular interactions.PMID:37689794 | DOI:10.1038/s41540-023-00305-5

Human blood vessel organoids reveal a critical role for CTGF in maintaining microvascular integrity

Sat, 09/09/2023 - 12:00
Nat Commun. 2023 Sep 9;14(1):5552. doi: 10.1038/s41467-023-41326-2.ABSTRACTThe microvasculature plays a key role in tissue perfusion and exchange of gases and metabolites. In this study we use human blood vessel organoids (BVOs) as a model of the microvasculature. BVOs fully recapitulate key features of the human microvasculature, including the reliance of mature endothelial cells on glycolytic metabolism, as concluded from metabolic flux assays and mass spectrometry-based metabolomics using stable tracing of 13C-glucose. Pharmacological targeting of PFKFB3, an activator of glycolysis, using two chemical inhibitors results in rapid BVO restructuring, vessel regression with reduced pericyte coverage. PFKFB3 mutant BVOs also display similar structural remodelling. Proteomic analysis of the BVO secretome reveal remodelling of the extracellular matrix and differential expression of paracrine mediators such as CTGF. Treatment with recombinant CTGF recovers microvessel structure. In this work we demonstrate that BVOs rapidly undergo restructuring in response to metabolic changes and identify CTGF as a critical paracrine regulator of microvascular integrity.PMID:37689702 | DOI:10.1038/s41467-023-41326-2

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