PubMed
Metabolomics analysis of pathways underlying radiation-induced salivary gland dysfunction stages
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
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
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
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
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
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
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
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
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
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
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
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
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
Potential nervous threat of nanoplastics to Monopterus albus: Implications from a metabolomics study
Sci Total Environ. 2023 Nov 17:168482. doi: 10.1016/j.scitotenv.2023.168482. Online ahead of print.ABSTRACTNanoplastics, as a new class of environmental pollutants, have been frequently detected in environmental media and organisms. Monopterus albus (M. albus) is an important economic aquatic product with a high dietary consumption. However, the potential biological effects of nanoplastics on M. albus remain unknown. In this study, the effects of polystyrene nanoplastics (PS-NPs) at different concentrations (0, 0.5, 1, 5 and 10 mg/L) on M. albus were investigated using an untargeted metabolomics approach. The results showed that 59, 44, 24, and 31 individual differential metabolites and 16, 9, 6, and 2 significant differential metabolic pathways were significantly changed in 0.5, 1, 5, and 10 mg/L respectively, indicating the greater effect of PS-NPs at the relatively low concentrations. After further analysis, there are four same significant differential metabolic pathways for the 0.5 and 1 mg/L groups, i.e., ABC transporters, cAMP signaling pathway, Neuroactive ligand-receptor interaction, and Synaptic vesicle cycle. In addition, there was one mutual differential metabolic pathway (Neuroactive ligand-receptor interaction) among the four groups, indicative of the probably universal nervous influence of nanoplastics on M. albus. In a word, the current work suggests that PS-NPs might affect the nervous systems of M. albus through disturbing their liver metabolism, and nanoplastics at relatively low concentrations may possess a greater effect, which provides significant information for assessing the toxic effect and exposure risk of nanoplastics to organisms in aquatic environment.PMID:37981139 | DOI:10.1016/j.scitotenv.2023.168482
Role of gut microbiota on regulation potential of Dendrobium officinale Kimura & Migo in metabolic syndrome: In-vitro fermentation screening and in-vivo verification in db/db mice
J Ethnopharmacol. 2023 Nov 17:117437. doi: 10.1016/j.jep.2023.117437. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium officinale Kimura & Migo (DEN) is a traditional medicine in China since Han dynasty. Decoction of its stem is often used in the treatment of Type-II diabetes (T2D), which is a typical metabolic disease accompanied with the impaired metabolic function of blood glucose and lipid.AIM OF THE STUDY: Our study aimed to investigate the role of gut microbiota in differentiating DEN from different sources and its related pathway in the alleviation of metabolic syndromes induced by T2D.MATERIALS AND METHODS: The aqueous extracts of four commercially available Dendrobium (DEN-1∼4) were prepared and screened through an in-vitro fermentation system. Based on their alterations in monosaccharide composition and short chain fatty acids (SCFA) formation during fermentation with db/db faecal fluid, one DEN extract was selected for further in vivo verification. The selected Dendrobium (DEN-4) was orally administered to db/db mice for 16 days once daily at the dosage of 200 mg/kg followed by evaluating its effect on blood glucose level, liver function and intestinal microenvironment including alterations of intestinal integrity and gut microbiota composition. In addition, liver metabolomics analysis was employed to reveal the related metabolic pathways.RESULTS: Different extent of SCFA formation and utilization of monosaccharides were observed for the extracts of four DEN from different sources with a negative correlation between SCFA level and the ratio of Utilized glucose/Utilized mannose observed in the in-vitro fermentation system with db/db faecal fluid. DEN-4 with the highest SCFA formation during the in-vitro fermentation was selected and exhibited significantly hypoglycaemic effect in db/db mice with the alleviation of hepatic steatosis and impaired lipid homeostasis. Further mechanistic studies revealed that orally administered DEN-4 could improve the intestinal integrity of db/db mice via elevating their tight junction protein (ZO-1 and Occludin) expression in the colon and improve the diversity of gut microbiota with enhanced formation of SCFA. Moreover, metabolomics and KEGG pathway analysis of liver tissues suggested that the alleviated metabolic syndrome in db/db mice by DEN-4 might possibly be achieved through activation of PPAR pathway.CONCLUSION: Our current study not only revealed the potential of gut microbiota in differentiating DEN from different sources, but also demonstrated that DEN exhibited its beneficial effect on the T2D induced metabolic syndrome possibly through enhancement of intestinal integrity and activation of PPAR pathway via gut-liver axis in db/db mice.PMID:37981116 | DOI:10.1016/j.jep.2023.117437
Toxin metalloproteinases exert a dominant influence on pro-inflammatory response and anti-inflammatory regulation in jellyfish sting dermatitis
J Proteomics. 2023 Nov 17:105048. doi: 10.1016/j.jprot.2023.105048. Online ahead of print.ABSTRACTToxin metalloproteinases are the primary components responsible for various toxicities in jellyfish venom, and there is still no effective specific therapy for jellyfish stings. The comprehension of the pathogenic mechanisms underlying toxin metalloproteinases necessitates further refinement. In this study, we conducted a differential analysis of a dermatitis mouse model induced by jellyfish Nemopilema nomurai venom (NnNV) samples with varying levels of metalloproteinase activity. Through skin tissue proteomics and serum metabolomics, the predominant influence of toxin metalloproteinase activity on inflammatory response was revealed, and the signal pathway involved in its regulation was identified. In skin tissues, many membrane proteins were significantly down-regulated, which might cause tissue damage. The expression of pro-inflammatory factors was mainly regulated by PI3K-Akt signaling pathway. In serum, many fatty acid metabolites were significantly down-regulated, which might be the anti-inflammation feedback regulated by NF-κB p65 signaling pathway. These results reveal the dermatitis mechanism of toxin metalloproteinases and provide new therapeutic targets for further studies. SIGNIFICANCE: Omics is an important method to analyze the pathological mechanism and discover the key markers, which can reveal the pathological characteristics of jellyfish stings. Our research first analyzed the impact of toxin metalloproteinases on jellyfish sting dermatitis by skin proteomics and serum metabolomics. The present results suggest that inhibition of toxin metalloproteinases may be an effective treatment strategy, and provide new references for further jellyfish sting studies.PMID:37981009 | DOI:10.1016/j.jprot.2023.105048
Phytochemical investigation and antioxidant properties of unripe tomato cultivars (Solanum lycopersicum L.)
Food Chem. 2023 Nov 10;438:137863. doi: 10.1016/j.foodchem.2023.137863. Online ahead of print.ABSTRACTUnripe tomatoes are among the main waste produced during tomato cultivation and processing. In this study, unripe tomatoes from seven different Italian cultivars have been investigated to evaluate their nutraceutical potential. Phytochemical investigation allowed shedding light on the identification of seventy-five bioactive compounds. The highest amount of polyphenolic and glycoalkaloids along with the high level of antioxidant activities was found in the Datterini tomatoes variety. The peculiarity of this variety is the high chlorogenic acid content, being ten times higher compared to the other cultivars examined. Moreover, the total α-tomatine amount has been found substantially higher (34.699 ± 1.101 mg/g dry weight) with respect to the other tomato varieties analyzed. Furthermore, the cultivars metabolomic profiles were investigated with the PCA approach. Based on Datterini cultivar's metabolomic profile, its waste-recovery could represent a good option for further added value products in pharmaceutical and nutraceutical areas with a high α-tomatine content.PMID:37980871 | DOI:10.1016/j.foodchem.2023.137863
Screening of an efficient cholesterol-lowering strain of Lactiplantibacillus plantarum 54-1 and investigation of its degradation molecular mechanism
Ultrason Sonochem. 2023 Nov 17;101:106698. doi: 10.1016/j.ultsonch.2023.106698. Online ahead of print.ABSTRACTIn this study, an efficient cholesterol-lowering strain of Lactiplantibacillus plantarum 54-1 was screened and its degradation molecular mechanism was investigated. Furthermore, a novel practical MRS medium for screening cholesterol-lowering lactic acid bacteria (LAB) was developed based on ultrasound treatment. L. plantarum 54-1 was found to have the highest ability to eliminate cholesterol (340.69 ± 5.87 µg/mL). According to SEM and the count of viable LAB results, the morphology of LAB in the cholesterol-containing medium developed in this experiment was close to the normal (full and smooth), and it can grow normally. Metabolomics revealed that L. plantarum 54-1 initially converted a portion of cholesterol to 7α-hydroxy-cholesterol and then to the key metabolite taurine, via the phosphotransferase system. These metabolites were further transformed into L-alanine, L-lysine, N6-Acetyl-L-lysine, (R)-b-aminoisobutyric acid, and 2-oxoarginine, through glycine, serine, and threonine metabolism, citrate cycle, D-arginine and D-ornithine metabolism, lysine degradation, and pyruvate metabolism pathways. Prokaryotic reference transcriptomics found that this may be mainly regulated by the bsh, phnE, ptsP, B0667_RS04545, and B0667_RSRS12300 genes, which was further validated by qPCR. Furthermore, molecular docking results demonstrated that 8 differential metabolites might bind to another portion of cholesterol via PI-PI conjugation and hydrophobic interactions and lower cholesterol via co-sedimentation. This study has strategic implications for developing probiotic powder food that lowers cholesterol.PMID:37980826 | DOI:10.1016/j.ultsonch.2023.106698
Colonization of chickens with competitive exclusion products results in extensive differences in metabolite composition in cecal digesta
Poult Sci. 2023 Oct 19;103(1):103217. doi: 10.1016/j.psj.2023.103217. Online ahead of print.ABSTRACTThe concept of competitive exclusion is well established in poultry and different products are used to suppress the multiplication of enteric pathogens in the chicken intestinal tract. While the effect has been repeatedly confirmed, the specific principles of competitive exclusion are less clear. The aim of the study was to compare metabolites in the cecal digesta of differently colonized chickens. Metabolites in the cecal contents of chickens treated with a commercial competitive exclusion product or with an experimental product consisting of 23 gut anaerobes or in control untreated chickens were determined by mass spectrometry. Extensive differences in metabolite composition among the digesta of all 3 groups of chickens were recorded. Out of 1,706 detected compounds, 495 and 279 were differently abundant in the chicks treated with a commercial or experimental competitive exclusion product in comparison to the control group, respectively. Soyasaponins, betaine, carnitine, glutamate, tyramine, phenylacetaldehyde, or 3-methyladenine were more abundant in the digesta of control chicks while 4-oxododecanedioic acid, nucleotides, dipeptides, amino acids (except for glutamate), and vitamins were enriched in the digesta of chickens colonized by competitive exclusion products. Metabolites enriched in the digesta of control chicks can be classified as of plant feed origin released in the digesta by degradative activities of the chicken. Some of these molecules disappeared from the digesta of chicks colonized by complex microbiota due to them being metabolized. Instead, nucleotides, amino acids, and vitamins increased in the digesta of colonized chicks as a consequence of the additional digestive potential brought to the cecum by microbiota from competitive exclusion products. It is therefore possible to affect metabolite profiles in the chicken cecum by its colonization with selected bacterial species.PMID:37980752 | DOI:10.1016/j.psj.2023.103217
Comparative analysis of hepatic transcriptomes and metabolomes of Changshun green-shell laying hens based on different green eggshell color intensities
Poult Sci. 2023 Oct 20;103(1):103220. doi: 10.1016/j.psj.2023.103220. Online ahead of print.ABSTRACTThe eggshell color of avian species is an important trait that is predominantly determined by the pigments biliverdin and protoporphyrin. Various factors affect eggshell pigment deposition and coloration; however, the underlying mechanisms remain unclear. We analyzed the hepatic transcriptomes and metabolomes of Changshun green-shell hens laying dark green and light green eggs to investigate the potential role of the liver in regulating the intensity of the green eggshell color. In total, 350 differentially expressed genes and 211 differentially altered metabolites were identified. Gene set enrichment analysis revealed that the enriched pathways and Gene Ontology (GO) terms were mainly associated with energy, immunity, and nutrient metabolism. Metabolite set enrichment analysis revealed that the enriched pathways were mainly associated with amino acid, vitamin, bile acid, and lipid metabolism. Moreover, gene-metabolite interaction network analysis revealed 1 subnetwork. Most genes and metabolites in this subnetwork were determined to be related to melanin metabolism and transport. In conclusion, our results suggest that hepatic melanin metabolism and transport are critical for eggshell coloration. Six candidate genes (CDKN2B, DDC, PYCR1, ABCG5, SLC3A1, and P2RX2) and 7 candidate metabolites (serotonin, 5-hydroxyindoleacetic acid, ornithine, acetylcholine, L-tryptophan, D-ornithine, and ADP) were suggested to play important roles in this process. Meanwhile, this study suggests that changes in hepatic energy metabolism, immune status, antioxidation activity, nutrient availability, and bile acid synthesis can impair eggshell coloration.PMID:37980748 | DOI:10.1016/j.psj.2023.103220