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

Hypericum perforatum L. protects against renal function decline in ovariectomy rat model by regulating expressions of NOS3 and AKT1 in AGE-RAGE pathway

Mon, 20/11/2023 - 12:00
Phytomedicine. 2023 Nov 10;123:155160. doi: 10.1016/j.phymed.2023.155160. Online ahead of print.ABSTRACTBACKGROUND: Hypericum perforatum L. (HPL) is a potential traditional Chinese medicine. It could promotes menopausal 'kidney-yin deficiency syndrome' that characterized by renal function decline. However, its potential pharmacological effect and mechanism remains unknown.OBJECTIVE: The aim of this study was to investigate whether HPL can improve menopausal renal function decline and to explore its mechanism of action.METHODS: The mainly ingredients of HPL were identified using UPLC-Q-TOF-MS/MS approach, and the potential therapeutic targets of HPL for renal function decline were chose via network pharmacology technique. The key therapeutic metabolites were selected through non-targeted metabolomic and chemometric methods. Then, the network were constructed and the key targets and metabolites were screened. At last, the validation experiments and mechanism exploring were adopted by using Immunofluorescence, enzyme-linked immunosorbent assay (ELISA), real-time PCR (RT-PCR), and western blotting assays.RESULTS: mainly ingredients of HPL were identified and determined 17 compounds and 29 targets were chose as mainly active compounds and potential therapeutic targets. Based on OVX induced renal decline rat model, after chemometric analysis, 59 endo-metabolites were selected as key therapeutic metabolites, and AGE-RAGE signal pathway in diabetes complications was enriched as the key pathway. By constructing a "disease-component-target" network, Hyperoside, Quercetrin, and quinic were selected as the key therapeutic compounds, and the AKT1 and NOS3 were selected as the key therapeutic targets. The results of ELISA, RT-PCR and western blot experiments indicated that HPL could rescue the abnormal expressions both of AKT1 and NOS3, as well as their related metabolites distortion.CONCLUSION: Our findings indicated that HPL regulated expression of AKT1 and NOS3 through modulating AGE-RAGE signaling pathway in OVX stimulated rats` renal dysfunction, implicating the potential values of HPL in menopause syndromes therapy.PMID:37984122 | DOI:10.1016/j.phymed.2023.155160

Integrated transcriptomics and metabolomics reveal specific phenolic and flavonoid accumulation in licorice (Glycyrrhiza uralensis Fisch.) induced by arbuscular mycorrhiza symbiosis under drought stress

Mon, 20/11/2023 - 12:00
Plant Physiol Biochem. 2023 Nov 11;205:108173. doi: 10.1016/j.plaphy.2023.108173. Online ahead of print.ABSTRACTArbuscular mycorrhizal (AM) symbiosis can strengthen plant defense against abiotic stress, such as drought, through multiple mechanisms; however, the specialized chemical defenses induced by AM symbiosis are largely unknown. In a pot experiment, licorice (Glycyrrhiza uralensis Fisch.) inoculated with and without arbuscular mycorrhizal fungus Rhizophagus irregularis Schenck & Smith were grown under well-watered or water deficit conditions. Transcriptomic and metabolomic analyses were combined to investigate licorice root specialized metabolism induced by AM symbiosis under drought stress. Results showed that mycorrhizal plants had few dead leaves, less biomass reduction, and less differentially expressed genes and metabolite features in response to drought compared with nonmycorrhizal plants. Transcriptomic and metabolomic data revealed that mycorrhizal roots generally accumulated lignin regardless of the water regime; however, the expression of genes involved in lignin biosynthesis was significantly downregulated by drought stress in mycorrhizal plants. By contrast, AM inoculation significantly decreased specialized metabolites accumulation, including phenolics and flavonoids under well-watered conditions, whereas these decreases turned to be nonsignificant under drought stress. Moreover, these specific phenolics and flavonoids showed significant drought-induced accumulation pattern in mycorrhizal roots. These results highlight that accumulation of specific root phenolics and flavonoids may support the drought tolerance of mycorrhizal plants.PMID:37984021 | DOI:10.1016/j.plaphy.2023.108173

Metabolic profiling of Oryza sativa seedlings under chilling stress using nanoliter electrospray ionization mass spectrometry

Mon, 20/11/2023 - 12:00
Food Chem. 2023 Nov 17;438:138005. doi: 10.1016/j.foodchem.2023.138005. Online ahead of print.ABSTRACTLow temperatures significantly impact on rice (Oryza sativa) yield and quality. Traditional metabolomic techniques, often involving time-consuming chromatography-mass spectrometry procedures, are currently in use. This study investigated metabolomic responses of rice seedlings under low-temperature stress using nanoliter electrospray ionization mass spectrometry (nanoESI-MS) in combination with multivariate analysis. Results revealed distinct metabolic profiles in 'Qiutianxiaoting' (japonica) and '93-11' (indica) rice seedlings. Among the 36 identified compounds in rice, seven key metabolites, comprising l-glutamic acid, asparagine, tryptophan, citric acid, α-linolenic acid, malic acid, and inositol, were identified as responsive to cold stress. Notably, malic acid content reached 1332.40 μg/g dry weight in Qiutianxiaoting and 1444.13 μg/g in 93-11. Both the qualitative and quantitative results of nanoESI-MS were further confirmed through gas chromatography-mass spectrometry validation. The findings highlight the potential of nanoESI-MS for rapidly characterizing crucial metabolites across diverse plant species under exposure to stress.PMID:37983997 | DOI:10.1016/j.foodchem.2023.138005

MetGENE: gene-centric metabolomics information retrieval tool

Mon, 20/11/2023 - 12:00
Gigascience. 2022 Dec 28;12:giad089. doi: 10.1093/gigascience/giad089.ABSTRACTBACKGROUND: Biomedical research often involves contextual integration of multimodal and multiomic data in search of mechanisms for improved diagnosis, treatment, and monitoring. Researchers need to access information from diverse sources, comprising data in various and sometimes incongruent formats. The downstream processing of the data to decipher mechanisms by reconstructing networks and developing quantitative models warrants considerable effort.RESULTS: MetGENE is a knowledge-based, gene-centric data aggregator that hierarchically retrieves information about the gene(s), their related pathway(s), reaction(s), metabolite(s), and metabolomic studies from standard data repositories under one dashboard to enable ease of access through centralization of relevant information. We note that MetGENE focuses only on those genes that encode for proteins directly associated with metabolites. All other gene-metabolite associations are beyond the current scope of MetGENE. Further, the information can be contextualized by filtering by species, anatomy (tissue), and condition (disease or phenotype).CONCLUSIONS: MetGENE is an open-source tool that aggregates metabolite information for a given gene(s) and presents them in different computable formats (e.g., JSON) for further integration with other omics studies. MetGENE is available at https://bdcw.org/MetGENE/index.php.PMID:37983749 | DOI:10.1093/gigascience/giad089

Machine Learning-Supported Enzyme Engineering toward Improved CO<sub>2</sub>-Fixation of Glycolyl-CoA Carboxylase

Mon, 20/11/2023 - 12:00
ACS Synth Biol. 2023 Nov 20. doi: 10.1021/acssynbio.3c00403. Online ahead of print.ABSTRACTGlycolyl-CoA carboxylase (GCC) is a new-to-nature enzyme that catalyzes the key reaction in the tartronyl-CoA (TaCo) pathway, a synthetic photorespiration bypass that was recently designed to improve photosynthetic CO2 fixation. GCC was created from propionyl-CoA carboxylase (PCC) through five mutations. However, despite reaching activities of naturally evolved biotin-dependent carboxylases, the quintuple substitution variant GCC M5 still lags behind 4-fold in catalytic efficiency compared to its template PCC and suffers from futile ATP hydrolysis during CO2 fixation. To further improve upon GCC M5, we developed a machine learning-supported workflow that reduces screening efforts for identifying improved enzymes. Using this workflow, we present two novel GCC variants with 2-fold increased carboxylation rate and 60% reduced energy demand, respectively, which are able to address kinetic and thermodynamic limitations of the TaCo pathway. Our work highlights the potential of combining machine learning and directed evolution strategies to reduce screening efforts in enzyme engineering.PMID:37983631 | DOI:10.1021/acssynbio.3c00403

Loss of function mutations at the tomato SSI2 locus impair plant growth and development by altering the fatty acid desaturation pathway

Mon, 20/11/2023 - 12:00
Plant Biol (Stuttg). 2023 Nov 20. doi: 10.1111/plb.13591. Online ahead of print.ABSTRACTThe stearoyl-ACP desaturase (SACPD) is a key enzyme in the regulation of saturated to unsaturated fatty acid ratio, playing a crucial role in regulating membrane stability and fluidity, as well as photosynthesis efficiency, which makes it an important research focus in crop species. This study reports the characterization and molecular cloning of pale dwarf (pad), a new tomato (Solanum lycopersicum L.) T-DNA recessive mutant, which exhibits a dwarf and chlorotic phenotype. Functional studies of the T-DNA tagged gene were conducted, including phylogenetic analysis, expression and metabolomic analyses, and generation of CRISPR/Cas9 knockout lines. The cloning of T-DNA flanking genomic sequences and a co-segregation analysis found the pad phenotype was caused by a T-DNA insertion disrupting the tomato homologue of the Arabidopsis SUPPRESSOR OF SALICYLIC ACID INSENSITIVITY 2 (SlSSI2), encoding a plastid localized isoform of SACPD. The phenotype of CRISPR/Cas9 SlSSI2 knockout lines confirmed that the morphological abnormalities in pad plants were due to SlSSI2 loss of function. Functional, metabolomic and expression analyses proved that SlSSI2 disruption causes deficiencies in 18:1 fatty acid desaturation and leads to diminished jasmonic acid (JA) content and increased salicylic acid (SA) levels. Overall, these results proved that SSI2 plays a crucial role in the regulation of polyunsaturated fatty acid profiles in tomato, and revealed that SlSSI2 loss of function results in an inhibited JA-responsive signalling pathway and a constitutively activated SA-mediated defence signalling response. This study lays the foundation for further research on tomato SACPDs and their role in plant performance and fitness.PMID:37983594 | DOI:10.1111/plb.13591

Metabolomic, Proteomic, and Single-Cell Proteomic Analysis of Cancer Cells Treated with the KRAS<sup>G12D</sup> Inhibitor MRTX1133

Mon, 20/11/2023 - 12:00
J Proteome Res. 2023 Nov 20. doi: 10.1021/acs.jproteome.3c00212. Online ahead of print.ABSTRACTMutations in KRAS are common drivers of human cancers and are often those with the poorest overall prognosis for patients. A recently developed compound, MRTX1133, has shown promise in inhibiting the activity of KRASG12D mutant proteins, which is one of the main drivers of pancreatic cancer. To better understand the mechanism of action of this compound, I performed both proteomics and metabolomics on four KRASG12D mutant pancreatic cancer cell lines. To obtain increased granularity in the proteomic observations, single-cell proteomics was successfully performed on two of these lines. Following quality filtering, a total of 1498 single cells were analyzed. From these cells, 3140 total proteins were identified with approximately 953 proteins quantified per cell. At 48 h of treatment, two distinct populations of cells can be observed based on the level of effectiveness of the drug in decreasing the total abundance of the KRAS protein in each respective cell, with results that are effectively masked in the bulk cell analysis. All mass spectrometry data and processed results are publicly available at www.massive.ucsd.edu at accessions PXD039597, PXD039601, and PXD039600.PMID:37983312 | DOI:10.1021/acs.jproteome.3c00212

Metabolomics analysis of pathways underlying radiation-induced salivary gland dysfunction stages

Mon, 20/11/2023 - 12:00
PLoS One. 2023 Nov 20;18(11):e0294355. doi: 10.1371/journal.pone.0294355. eCollection 2023.ABSTRACTSalivary gland hypofunction is an adverse side effect associated with radiotherapy for head and neck cancer patients. This study delineated metabolic changes at acute, intermediate, and chronic radiation damage response stages in mouse salivary glands following a single 5 Gy dose. Ultra-high performance liquid chromatography-mass spectrometry was performed on parotid salivary gland tissue collected at 3, 14, and 30 days following radiation (IR). Pathway enrichment analysis, network analysis based on metabolite structural similarity, and network analysis based on metabolite abundance correlations were used to incorporate both metabolite levels and structural annotation. The greatest number of enriched pathways are observed at 3 days and the lowest at 30 days following radiation. Amino acid metabolism pathways, glutathione metabolism, and central carbon metabolism in cancer are enriched at all radiation time points across different analytical methods. This study suggests that glutathione and central carbon metabolism in cancer may be important pathways in the unresolved effect of radiation treatment.PMID:37983277 | DOI:10.1371/journal.pone.0294355

Spatially Resolved Co-Imaging of Polyhalogenated Xenobiotics and Endogenous Metabolites Reveals Xenobiotic-Induced Metabolic Alterations

Mon, 20/11/2023 - 12:00
Environ Sci Technol. 2023 Nov 20. doi: 10.1021/acs.est.3c05817. Online ahead of print.ABSTRACTA large group of polyhalogenated compounds has been added to the list of persistent organic pollutants in a global convention endorsed by over 100 nations. Once entering the biotas, these pollutants are transported to focal sites of toxicological action and affected endogenous metabolites, which exhibited distinct tissue or organ distribution patterns. However, no study is available to achieve simultaneous mapping of the spatial distributions of xenobiotics and endogenous metabolites for clarifying the molecular mechanism of toxicities. Herein, we present a sensitive mass spectrometry imaging method─tetraphenyl phosphonium chloride-enhanced ionization coupled with air flow-assisted ionization-Orbitrap mass spectrometry─which simultaneously determined the spatial distributions of polyhalogenated xenobiotics and endogenous metabolites. The spatially resolved toxicokinetics and toxicodynamics of typical polyhalogenated compounds (chlorinated paraffins (CPs) and hexabromocyclododecane (HBCD)) were assessed in zebrafish. Co-imaging of polyhalogenated compounds and metabolites visualized the major accumulation organs and maternal transfer of HBCD and CPs, and it clarified the reproductive toxicity of HBCD. CPs were accumulated in the liver, heart, and brain and decreased the concentrations of polyamine/inosine-related metabolites and lipid molecules in these organs. HBCD accumulated in the ovary and was effectively transferred to eggs, and it also disrupted normal follicular development and impaired the production of mature eggs from the ovary by inhibiting expressions of the luteinizing hormone/choriogonadotropin receptor gene. The toxic effects of metabolic disruptions were validated by organ-specific histopathological examinations. These results highlight the necessity to assess the distributions and bioeffects of pollutants in a spatial perspective.PMID:37983170 | DOI:10.1021/acs.est.3c05817

Dihydroartemisinin inhibits melanoma migration and metastasis by affecting angiogenesis

Mon, 20/11/2023 - 12:00
Phytother Res. 2023 Nov 19. doi: 10.1002/ptr.8065. Online ahead of print.ABSTRACTTumor angiogenesis is critical for tumor metastasis by providing oxygen, nutrients, and metastatic pathways. As a potential anti-angiogenic agent, Dihydroartemisinin (DHA) can effectively inhibit tumor metastasis. However, the mechanism how it regulates angiogenesis to affect tumor metastasis has not been fully clarified. To investigate the mechanisms of how DHA regulates melanoma progression. In this study, bioinformatics methods were used to analyze the correlation between angiogenesis and melanoma metastasis. Then, B16F10, A375, HUVECs and mouse metastasis models were adapted to clarify the inhibition of DHA in melanoma. GESA analysis revealed melanoma metastasis significantly positive correlated with angiogenesis. Meanwhile, DHA significantly decreased melanoma nodules and lung wet weight in metastatic tumor mice, and inhibited the expression of the angiogenic marker CD31 in vitro and in vivo. Similarly, DHA inhibited the expression of the angiogenic signal molecule VEGFR2 in A375 and B16F10 cells, and significantly suppressed the formation of their tubular structures. DHA-treated supernatants significantly inhibited the tubule-forming ability as well as lateral and longitudinal migration ability of HUVECs compared with untreated melanoma cell supernatants. Screening yielded the angiogenic pathways HIF-1α/VEGF, PI3K/ATK/mTOR associated with melanoma metastasis, and DHA may inhibit tumor metastasis by inhibiting these angiogenic pathways in melanoma cells to inhibit tumor metastasis. Further non-targeted metabolomics analysis revealed that DHA-treated model mice produced differential metabolites that were also associated with angiogenic pathways. DHA inhibits melanoma invasion and metastasis by mediating angiogenesis. These results have important implications for the potential use of DHA in treatment of melanoma.PMID:37982352 | DOI:10.1002/ptr.8065

The practice of fecal microbiota transplantation in inflammatory bowel disease

Mon, 20/11/2023 - 12:00
Intest Res. 2023 Nov 21. doi: 10.5217/ir.2023.00085. Online ahead of print.ABSTRACTCurrent evidence posits a central role for gut microbiota and the metabolome in the pathogenesis and progression of inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) has been established as a means to manipulate this microbiome safely and sustainably. Several aspects of the technical improvement including pretreatment with antibiotics, use of frozen stool samples as well as short donor-to-recipient time are proposed to improve its response rates. Its efficacy in ulcerative colitis has been proven in clinical trials while data is emerging for Crohn's disease. This review describes briefly the biology behind FMT, the available evidence for its use in IBD, and the host, recipient and procedural factors which determine the clinical outcomes.PMID:37981746 | DOI:10.5217/ir.2023.00085

Dysregulations in hemostasis, metabolism, immune response, and angiogenesis in post-acute COVID-19 syndrome with and without postural orthostatic tachycardia syndrome: a multi-omic profiling study

Mon, 20/11/2023 - 12:00
Sci Rep. 2023 Nov 19;13(1):20230. doi: 10.1038/s41598-023-47539-1.ABSTRACTPost-acute COVID-19 (PACS) are associated with cardiovascular dysfunction, especially postural orthostatic tachycardia syndrome (POTS). Patients with PACS, both in the absence or presence of POTS, exhibit a wide range of persisting symptoms long after the acute infection. Some of these symptoms may stem from alterations in cardiovascular homeostasis, but the exact mechanisms are poorly understood. The aim of this study was to provide a broad molecular characterization of patients with PACS with (PACS + POTS) and without (PACS-POTS) POTS compared to healthy subjects, including a broad proteomic characterization with a focus on plasma cardiometabolic proteins, quantification of cytokines/chemokines and determination of plasma sphingolipid levels. Twenty-one healthy subjects without a prior COVID-19 infection (mean age 43 years, 95% females), 20 non-hospitalized patients with PACS + POTS (mean age 39 years, 95% females) and 22 non-hospitalized patients with PACS-POTS (mean age 44 years, 100% females) were studied. PACS patients were non-hospitalized and recruited ≈18 months after the acute infection. Cardiometabolic proteomic analyses revealed a dysregulation of ≈200 out of 700 analyzed proteins in both PACS groups vs. healthy subjects with the majority (> 90%) being upregulated. There was a large overlap (> 90%) with no major differences between the PACS groups. Gene ontology enrichment analysis revealed alterations in hemostasis/coagulation, metabolism, immune responses, and angiogenesis in PACS vs. healthy controls. Furthermore, 11 out of 33 cytokines/chemokines were significantly upregulated both in PACS + POTS and PACS-POTS vs. healthy controls and none of the cytokines were downregulated. There were no differences in between the PACS groups in the cytokine levels. Lastly, 16 and 19 out of 88 sphingolipids were significantly dysregulated in PACS + POTS and PACS-POTS, respectively, compared to controls with no differences between the groups. Collectively, these observations suggest a clear and distinct dysregulation in the proteome, cytokines/chemokines, and sphingolipid levels in PACS patients compared to healthy subjects without any clear signature associated with POTS. This enhances our understanding and might pave the way for future experimental and clinical investigations to elucidate and/or target resolution of inflammation and micro-clots and restore the hemostasis and immunity in PACS.PMID:37981644 | DOI:10.1038/s41598-023-47539-1

Unrevealing the in vitro impacts of Cereus jacamaru DC. cladodes flour on potentially probiotic strains, selected bacterial populations, and metabolic activity of human intestinal microbiota

Sun, 19/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 2):113658. doi: 10.1016/j.foodres.2023.113658. Epub 2023 Nov 3.ABSTRACTThis study investigated the potential impacts of the flour from Cereus jamacaru cactus cladodes (CJF), a cactus native to the Brazilian Caatinga biome, on the growth and metabolism of different potentially probiotic strains, as well as on the abundance of selected intestinal bacterial populations and microbial metabolic activity during in vitro colonic fermentation with a pooled human fecal inoculum. Cultivation of the probiotics in a medium with C. jamacaru cladodes flour (20 g/L) resulted in viable cell counts of up to 9.8 log CFU/mL, positive prebiotic activity scores (0.73-0.91), decreased pH and sugar contents, and increased lactic, acetic, and propionic acid production over time, indicating enhanced probiotic growth and metabolic activity. CJF overall increased the relative abundance of Lactobacillus spp./Enterococcus spp. (2.12-3.29%) and Bifidobacterium spp. (4.08-4.32%) and decreased the relative abundance of Bacteroides spp./Prevotella spp. (8.35-6.81%), Clostridium histolyticum (6.91-3.59%), and Eubacterium rectale/Clostridium coccoides (7.70-3.95%) during 48 h of an in vitro colonic fermentation using a pooled human fecal inoculum. CJF stimulated the microbial metabolic activity, with decreased pH, sugar consumption, lactic and short-chain fatty acid production, alterations in overall metabolic profiling and phenolic compound contents, and maintenance of high antioxidant capacity during colonic fermentation. These results show that CJF stimulated the growth and metabolic activity of distinct potential probiotics, increased the relative abundance of beneficial intestinal bacterial groups, and stimulated microbial metabolism during in vitro colonic fermentation. Further studies using advanced molecular technologies and in vivo experimental models could forward the investigation of the potential prebiotic properties of CJF.PMID:37981375 | DOI:10.1016/j.foodres.2023.113658

Lipidomics insight on differences in lipid profiles and phytosterol compositions of coconut oils extracted by classical and green solvents

Sun, 19/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 2):113653. doi: 10.1016/j.foodres.2023.113653. Epub 2023 Nov 2.ABSTRACTSearching for green and ecofriendly solvents to replace classical solvents for industrial scale extraction of coconut oil is of great interest. To explore these possibilities, this study performed comprehensive comparative analyses of lipid profiles and phytosterol compositions in coconut oils obtained by extraction with n-hexane, absolute ethyl alcohol, deep eutectic solvent/n-hexane, dimethyl carbonate (DME) and cyclopentyl methyl ether (CPME) using a foodomics approach. Results indicated that CPME (64.23 g/100 g dry matter) and DME (65.64 g/100 g dry matter) showed comparable capacity for total lipid extraction of total lipids to classical solvents (63.5-65.66 g/100 g dry matter). Considering the phytosterol yield, CPME (644.26 mg/kg) exhibited higher selectivity than other solvents (535.64-622.13 mg/kg). No significant difference was observed in the fatty acid composition of coconut oil by the different solvents assayed. Additionally, total 468 lipid molecules were identified in the samples. For glycerolipid and sphingolipid, the five solvents showed comparable extraction capabilities. However, CPME exhibited higher extraction efficiency of polar lipids (glycerophospholipid and saccharolipid) than other solvents. Overall, these results may be a useful guide for the application of green solvents in industrial production of coconut oil.PMID:37981374 | DOI:10.1016/j.foodres.2023.113653

Integrated multi-omic analysis reveals the cytokinin and sucrose metabolism-mediated regulation of flavone glycoside biosynthesis by MeJA exposure in Ficus pandurata Hance

Sun, 19/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 2):113680. doi: 10.1016/j.foodres.2023.113680. Epub 2023 Nov 6.ABSTRACTFicus pandurata Hance (FPH) holds a rich history as a traditional Chinese botanical remedy, utilized both as a culinary condiment and a medicinal intervention for diverse ailments. This study focuses on enhancing FPH's therapeutic potential by subjecting it to exogenous methyl jasmonate (MeJA) treatment, a strategy aimed at elevating the levels of active constituents to align with clinical and commercial requirements. Employing metabolomics, the impact of MeJA treatment on the lipid and flavonoid profiles of FPH leaves was investigated, revealing a marked increase in flavone glycosides, a subset of flavonoids. Investigation into the regulatory mechanism governing flavone glycoside biosynthesis uncovered elevated expression of structural genes associated with flavonoid production in response to MeJA exposure. Global endogenous hormone analysis pinpointed the selective activation of JA and cytokinin biosynthesis following MeJA treatment. Through a comprehensive integration of transcriptomic and metabolomic data, the cooperative stimulation of glucosyltransferase activity, alongside the JA and cytokinin signaling pathways, orchestrated by MeJA were explored. Furthermore, genes linked to sucrose metabolism exhibited heightened expression, concomitant with a noteworthy surge in antioxidant activity subsequent to MeJA treatment. These findings validate the augmentation of FPH leaf antioxidant capacity through MeJA intervention, while also offering profound insights into the regulatory role of MeJA in flavone glycoside biosynthesis, mediated by the interplay between cytokinin and sucrose metabolism pathways.PMID:37981372 | DOI:10.1016/j.foodres.2023.113680

Effects of lactic acid bacteria-derived fermented feed on the taste and quality of duck meat

Sun, 19/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 2):113679. doi: 10.1016/j.foodres.2023.113679. Epub 2023 Nov 5.ABSTRACTThe present study aimed to examine the impact of lactic acid bacteria- fermented feed (FF) on the taste and quality of duck meat, in addition to elucidating the potential metabolomic mechanism at play. The findings revealed that ducks fed with FF exhibited elevated pH levels and reduced cooking loss in their meat when compared to the control group. In addition, the sensory evaluation and e-tongue analysis revealed that the tenderness, juiciness, umami, richness, saltiness, and sweetness of duck meat were all enhanced by feeding FF. Moreover, an examination of the metabolome using 1H nuclear magnetic resonance (1H NMR) identified the principal differential metabolites that exhibited a correlation with taste, which included 2-aminoadipate, glucose, glycine, N-acetylcysteine, niacinamide, proline, and threonine. Furthermore, the differential metabolites that exhibited the greatest enrichment in duck meat could be primarily traced to glutathione metabolism, glycine, serine and threonine metabolism, taurine and hypotaurine metabolism. The potential factors contributing to the effect of FF and basic commercial duck feed (CF) were found to be primarily regulated via the aforementioned metabolic pathways. The study, therefore, offers a viable approach for enhancing the taste and quality of duck meat.PMID:37981371 | DOI:10.1016/j.foodres.2023.113679

A comparative metabolomics study of polyphenols in highland barley (Hordeum vulgare L.) grains with different colors

Sun, 19/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 2):113672. doi: 10.1016/j.foodres.2023.113672. Epub 2023 Nov 4.ABSTRACTHighland barley (HB) grains are gaining increasing popularity owing to their high nutritional merits. However, only limited information is available on the metabolic profiles of HB grains polyphenols, especially the difference of polyphenols in different colors of HB. In this study, we determined the metabolic profiles of black, blue, and white HB grains via an ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS)-based metabolomics. A total of 402 metabolites were identified, among which 198, 62, and 189 metabolites displayed different accumulation patterns in the three comparison groups (WHB vs. BKHB, WHB vs. BEHB, BEHB vs. BKHB), respectively. In particular, flavonoids and phenolic acids contents displayed considerable differences among the three HB cultivars. The phenolics content of black HB was relatively high. Additionally, "Flavonoid biosynthesis" and "flavone and flavonol biosynthesis" were the significantly enriched pathways. In conclusion, this study provides comprehensive insights into the adequate utilization and development of novel HB-based functional foods.PMID:37981367 | DOI:10.1016/j.foodres.2023.113672

Unraveling symbiotic microbial communities, metabolomics and volatilomics profiles of kombucha from diverse regions in China

Sun, 19/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 2):113652. doi: 10.1016/j.foodres.2023.113652. Epub 2023 Nov 2.ABSTRACTKombucha is a natural fermented beverage (mixed system). This study aimed to unravel the signatures of kombucha in China to achieve tailor-made microbial consortium. Here, biochemical parameters, microbiome, metabolite production and volatile profile were comprehensively compared and characterized across four regions (AH, HN, SD, SX), both commonalities and distinctions were highlighted. The findings revealed that yeast species yeast Starmerella, Zygosaccharomyces, Dekkera, Pichia and bacterium Komagataeibacter, Gluconobacter were the most common microbes. Additionally, the composition, distribution and stability of microbial composition in liquid phase were superior to those in biofilm. The species diversity, differences, marker and association were analyzed across four areas. Metabolite profiles revealed a total of 163 bioactive compounds (23 flavonoids, 13 phenols), and 68 differential metabolites were screened and identified. Moreover, the metabolic pathways of phenylpropanoids biosynthesis were closely linked with the highest number of metabolites, followed by flavonoid biosynthesis. Sixty-five volatile compounds (23 esters) were identified. Finally, the correlation analysis among the microbial composition and volatile and functional metabolites showed that Komagataeibacter, Gluconolactone, Zygosacchaaromycess, Starmerella and Dekkera seemed closely related to bioactive compounds, especially Komagataeibacter displayed positive correlations with 1-hexadecanol, 5-keto-D-gluconate, L-malic acid, 6-aminohexanoate, Starmerella contributed greatly to gluconolactone, thymidine, anabasine, 2-isopropylmalic acid. Additionally, Candida was related to β-damascenone and α-terpineol, and Arachnomyces and Butyricicoccus showed the consistency of associations with specific esters and alcohols. These findings provided crucial information for creating a stable synthetic microbial community structure, shedding light on fostering stable kombucha and related functional beverages.PMID:37981364 | DOI:10.1016/j.foodres.2023.113652

Influence of spontaneous, "pied de cuve" and commercial dry yeast fermentation strategies on wine molecular composition and sensory properties

Sun, 19/11/2023 - 12:00
Food Res Int. 2023 Dec;174(Pt 2):113648. doi: 10.1016/j.foodres.2023.113648. Epub 2023 Oct 29.ABSTRACTWhile most producers in recent decades have relied on commercial yeasts (ADY) as their primary choice given their reliability and reproducibility, the fear of standardising the taste and properties of wine has led to the employment of alternative strategies that involve autochthonous yeasts such as pied de cuve (PdC) and spontaneous fermentation (SF). However, the impact of different fermentation strategies on wine has been a subject of debate and speculation. Consequently, this study describes, for the first time, the differences between the three kinds of fermentation at the metabolomic, chemical, and sensory levels in two wines: Chardonnay and Pinot Noir. The results showed how the yeast chosen significantly impacted the molecular composition of the wines, as revealed by metabolomic analysis that identified biomarkers with varying chemical compositions according to the fermentation modality. Notably, higher numbers of lipid markers were found for SF and PdC than ADY, which contained more peptides. Key molecules from the metabolic amino acid pathway, which are addressed in this article, showed evidence of such variations. In addition, the analysis of volatile aromatic compounds revealed an increase in groups of compounds specific to each fermentation. The sensorial analysis of Chardonnay wine showed a more qualitative sensory outcome (Higher fruit intensity) for ADY and SF compared to PdC. Our finding challenges the common speculation among wine producers that autochthonous yeast fermentations may offer greater complexity and uniqueness in comparison to commercial yeast fermentations.PMID:37981362 | DOI:10.1016/j.foodres.2023.113648

Flunitrazepam and its metabolites compromise zebrafish nervous system functionality: An integrated microbiome, metabolome, and genomic analysis

Sun, 19/11/2023 - 12:00
Environ Pollut. 2023 Nov 17:122949. doi: 10.1016/j.envpol.2023.122949. Online ahead of print.ABSTRACTThe psychotropic drug flunitrazepam (FLZ) is frequently detected in aquatic environments, yet its neurotoxicity to aquatic organisms has not received sufficient attention. In this study, microbiome, metabolome, and genome analyses were conducted to study the effects of FLZ and its metabolite 7-aminoflunitrazepam (7-FLZ) on the zebrafish nervous system and understand their toxic mechanisms. The results demonstrated that drug exposure induced gut dysbiosis, decreased short-chain fatty acids and promoted the production of lipopolysaccharides (LPS). LPS entered the brain and interacted with Toll-like receptors to cause neuroinflammation by upregulating the expression of proinflammatory cytokines TNFα and NF-κB. The increased ratio of S-adenosylmethionine to S-adenosylhomocysteine in brain tissues indicated abnormal expression of Dnmt1 gene. Whole-genome bisulfite sequencing displayed an increase in differentially methylated regions (DMRs) associated-genes and pertinent biological pathways encompassed the MAPK signaling pathway, calcium signaling pathway, and Wnt signaling pathway. Correlation analysis confirmed connections between gut microbiota, their metabolites, inflammatory factors, and DNA methylation-related markers in brain tissue. These findings indicate that while the toxicity is somewhat reduced in metabolized products, both FLZ and 7-FLZ can induce DNA methylation in brain tissue and ultimately affect the biological function of the nervous system by disrupting gut microbiota and their metabolites.PMID:37981184 | DOI:10.1016/j.envpol.2023.122949

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