PubMed

Food Res Int. 2024 Nov;196:115078. doi: 10.1016/j.foodres.2024.115078. Epub 2024 Sep 13.ABSTRACTCucumber is a widely consumed vegetable crop known for its rich nutrient composition and distinctive flavor, influenced by both volatile and non-volatile compounds. Grafting and delayed harvesting are crucial strategies for increasing cucumber yield. The present study investigates the impact of delayed harvesting at different developmental stages and grafting on the metabolic profile, flavor, and overall quality of cucumber fruits Yuxiu 2 (YX) using UPLC-MS/MS and GC-MS/MS techniques. The results indicate that delayed harvesting of YX led to significant increases in length, diameter, and weight from 12 to 24 days after pollination (DAP), with minimal growth beyond 24 DAP. However, grafting did not affect these physical parameters compared to self-rooted plants. Furthermore, metabolic profiling reveals that delayed harvesting enhances the concentration of certain non-volatile metabolites, including alkaloids, organic acids, and phenolic acids, while leading to a reduction in flavonoid contents. Overall, 140 non-volatile and 26 volatile differential metabolites were screened at three developmental stages. Notably, four new organic acids (6-amino hexanoic acid, 5-amino valeric acid, 1-hydroxy-2-naphthoic acid, and succinic semialdehyde) and three novel alkaloids (3-indole acetonitrile, epinephrine, and serotonin) were identified. Volatile compounds, such as aldehydes, esters, terpenes, alcohols, and ketones, exhibit a peak in concentration at 24 DAP, followed by a decline. The characteristic cucumber flavor compound, (E,Z)-2,6-nonadienal, remains consistent across all developmental stages. In grafted cucumber fruits, a total of 113 non-volatile and 11 volatile differential metabolites were screened, and among them, ten unique non-volatile metabolites were detected in grafted fruits, contributing to the sour and bitter taste of cucumbers. Moreover, some of the metabolites like (1S,4S,4aR)-1-isopropyl-4-methyl-7-methylene-1,2,3,4,4a,5,6,7-octahydronaphthalene with pentylenetetrazol contribute to an undesirable camphor-like odor. The study concludes that while delayed harvesting and grafting practices can increase cucumber yield, they also significantly alter the fruit's metabolic profile, impacting taste and flavor.PMID:39614565 | DOI:10.1016/j.foodres.2024.115078

Food Res Int. 2024 Nov;196:115026. doi: 10.1016/j.foodres.2024.115026. Epub 2024 Sep 6.ABSTRACTMorganella morganii is a spoilage microorganism in fish products that produces harmful biogenic amines (BAs). It has been discovered that Lactiplantibacillus plantarum His6 can inhibit the growth of this bacterium. The aim of this study was to quantitatively assess the inhibitory impact of the bioprotective culture Lpb. plantarum His6 on M. morganii YC16 in the matrix (fish and rice) using predictive microbiology models, and elucidate the interaction mechanism through untargeted metabolomics. The mathematical model results showed the inhibition effect of Lpb. plantarum His6 on M. morganii YC16 was dependent on temperature and inoculation concentration. In addition, the simultaneous growth of Lpb. plantarum His6 and M. morganii YC16 could be well simulated with the Lotka-Volterra model. Furthermore, significant decreased in histamine levels was observed in co-(1:3) at 25 °C. Finally, based on the metabolomics data, it was speculated that Lpb. plantarum His6 may enhance bacteriocin production while reducing the yield of glycerophospholipids and fatty acids associated with outer membrane formation, thereby inhibiting the growth of M. morganii YC16. These findings provide valuable insights into the interaction behavior and mechanism of Lpb. plantarum His6 and M. morganii YC16 in co-culture, facilitating the design of the biopreservation strategies for fish products.PMID:39614548 | DOI:10.1016/j.foodres.2024.115026

Food Res Int. 2024 Nov;196:115121. doi: 10.1016/j.foodres.2024.115121. Epub 2024 Sep 21.ABSTRACTThe objective of this study was to investigate the immunomodulatory effects of whey protein isolate (WPI)-galacto-oligosaccharide conjugates following dynamic high-pressure microfluidics pretreatment (DHPM) in cyclophosphamide-induced immunosuppressed mice. DHPM facilitated the conjugation of WPI and galacto-oligosaccharide, and inhibited the generation of fluorescent advanced glycation end products (AGEs) and pentosidine. The conjugates demonstrated a significant immune recovery effect on CTX-induced immunosuppressed mice, as evidenced by the enhancement of IgG antibody levels (from 3.5 to 4.1) and the reduction of the levels of immunosuppressive effector factors TGF-β (from 148.1 to 111.2) and IFN-γ (from 34.4 to 17.9). Furthermore, the conjugates exhibited a notable ability to repair histological lesion in the spleen of CTX-induced immunosuppressed mice. Spleen transcriptomics revealed that the Marco, Klrc3 and Cd209b genes were associated with the immune enhancement activity of the conjugates. Metabolomic analysis identified arginine biosynthesis, sphingolipid metabolism, alanine, aspartate and glutamate metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis as key pathways in the immune enhancement activity of the conjugates. Metabolomics combined with transcriptomics indicated the importance of macrophage activation in the restoration of immunosuppressed mice's immunity by the conjugates. Therefore, the improvement in immunity observed with WPI-galacto-oligosaccharide conjugates may be related to the activation of macrophages.PMID:39614521 | DOI:10.1016/j.foodres.2024.115121

Food Res Int. 2024 Nov;196:115112. doi: 10.1016/j.foodres.2024.115112. Epub 2024 Sep 21.ABSTRACTTo illustrate the development of chemical properties and characteristic flavor of Hainan Dayezhong black tea, the tea shoots under various manufacturing process were sampled and applied to targeted/widely-targeted metabolomic, transcriptomic, chemometric, and electronic sensory determinations. Totally, 2419 metabolites were identified in this study, of which 20 metabolites were selected as the biomarkers, mainly including amino acids, lipids, and pyrimidine derivatives. The metabolomic-transcriptomic integrated analysis indicated carbon fixation, flavonoid biosynthesis and amino acid metabolism were the major metabolic pathways over manufacturing process of Hainan Dayezhong black tea. The targeted metabolomic detection indicated the accumulations of free amino acids and reduction of total catechins, flavonol glycosides collectively contributed to the development of black tea taste; additionally, the antioxidative properties were decreasing along the production process. These results suggest that the tradeoff between bioactivity components and antioxidative capacity contribute to the characteristic flavor of Hainan Dayezhong black tea.PMID:39614518 | DOI:10.1016/j.foodres.2024.115112

Food Res Int. 2024 Nov;196:115109. doi: 10.1016/j.foodres.2024.115109. Epub 2024 Sep 20.ABSTRACTFine-flavored chocolates are distinguished by their complex and distinct flavor profiles, which includes notes such as floral, fruity, nutty, and spicy. This study sought to modulate the flavor development of chocolates by establishing controlled processing conditions during the transformation from seed to bean in a laboratory setting, to produce superior quality chocolates. Our experimental setup comprised two varying temperature levels (30 °C and 45 °C) and three organic acids (OAs: acetic, lactic, and citric acids) at concentrations of 1-30 g/L to adjust the pH of the transformation system. Our study focused on how these conditions affect the development of distinct flavor profiles in chocolate bars, emphasizing the enhancement of fine-flavor notes. Flavor development was monitored through the untargeted metabolomics of cocoa beans and analyzing the volatile compounds and sensory profiles of the resultant chocolates. This study revealed that OA concentration markedly influenced metabolite formation, particularly affecting peptides, volatile organic compounds, and flavor notes. Chocolates derived from seeds processed with 30 g/L acid solutions demonstrated enhanced fruitiness and acidity, whereas those processed with 1 g/L acid solutions exhibited pronounced nuttiness and cocoa taste attributes but lower acidity. These findings underscore the significance of meticulously managing flavor development processes to produce fine-flavored chocolates with unique aromatic profiles. Crucially, variables in the controlling process, such as temperature and pH, are essential for fine-tuning flavor attributes, enabling the correlation and identification of key quality biomarkers to elucidate flavor development pathways.PMID:39614516 | DOI:10.1016/j.foodres.2024.115109

Food Res Int. 2024 Nov;196:115093. doi: 10.1016/j.foodres.2024.115093. Epub 2024 Sep 16.ABSTRACTLactic acid bacteria (LAB) fermentation can enhance the quality and flavor characteristics of fruit juice. Herein, the impact of individual Lactiplantibacillus plantarum subsp. plantarum (L. plantarum) or Streptococcus thermophilus (S. thermophilus) and co-fermentation of them on jujube juice was compared, and their quality characteristics, volatile and non-volatile compounds were investigated. The results showed that the co-fermentation of selected LAB strains effectively improved the quality of fermented jujube juice (FJJ) as expected, and the types and content of volatile organic compounds (VOCs) increased in FJJs. Among them, the co-fermented sample posed relatively high content of aroma-active compounds with OAV ≥1 (nonanal, decanal, etc), benzaldehyde and acids compared with others, contributing to a more attractive and pleasant flavor. Moreover, non-targeted metabolomic analysis identified 114 and 79 differential metabolites (DMs) between co-fermented and L. plantarum fermented or S. thermophilus fermented samples, respectively. Notably, carboxylic acids and their derivative metabolites as well as organic acids were the crucial components affecting the quality of FJJ. Furthermore, metabolic pathways of DMs of different samples were predominantly enriched in "biosynthesis" and "metabolism", such as aline, leucine, and isoleucine biosynthesis pathway. Therefore, co-fermentation could enrich the acids, essential amino acid, and VOCs, thereby improving its quality and flavor characteristics. The correlation analysis revealed that most of key VOCs were positively or negatively correlated with D-galacturonate, indicating the importance of D-galactose pathway. Thus, this study provided a theoretical foundation for enhancing the quality and flavor of jujube juice through LAB co-fermentation, offering valuable insights for improving the juice processing.PMID:39614506 | DOI:10.1016/j.foodres.2024.115093

Food Res Int. 2024 Nov;196:115080. doi: 10.1016/j.foodres.2024.115080. Epub 2024 Sep 14.ABSTRACTSichuan shai vinegar (SSV) is an acidic condiment with a long history and unique flavor. Aging is an important production process that determines the unique flavor of shai vinegar. This study compared the differences in physicochemical properties, volatile flavor, and non-volatile flavor substances between the constant temperature aging and natural aging methods of SSV Cupei. The results showed that the total acid and amino acid nitrogen content in naturally aged vinegar was higher than that in constant temperature aged vinegar. Furthermore, 20 different volatile flavor substances and 65 different non-volatile flavor substances were obtained after 21 and 25 days of constant temperature aging and 1, 3, and 5 years of natural aging SSV samples. This indicates that the temperature environment during natural aging was more moderate, allowing acidic compounds to form and stably exist in the aging environment. Correlation analysis further demonstrated that there were more differentiated non-volatile substances significantly related to the Maillard reaction under constant temperature aging condition and related to antioxidant activity under natural aging condition. The results of this study provide a comprehensive understanding of the characteristics and applications of the two aging methods of SSV and guide strategy for factories in the selection of aging methods.PMID:39614502 | DOI:10.1016/j.foodres.2024.115080

Food Res Int. 2024 Nov;196:115056. doi: 10.1016/j.foodres.2024.115056. Epub 2024 Sep 7.ABSTRACTAnthocyanins are natural plant metabolites that are beneficial for human health. In order to study the fruit coloring mechanism mediated by anthocyanin biosynthesis in three currant varieties (white currant, red currant and black currant), we used a combination of transcriptomics and metabolomics analyses. Our comprehensive examination revealed that anthocyanins play a pivotal role in regulating the red and purple hues of black currant and red currant fruits. Specifically, Delphinidin-3-O-rutinoside, Pelargonidin-3-O-rutinoside, Cyanidin-3-O-rutinoside, Cyanidin-3,5-O-diglucoside, Cyanidin-3-O-rutinoside-5-O-glucoside and Petunidin-3-O-glucoside emerged as key anthocyanins in black currant, while Cyanidin-3-O-rutinoside (Keracyanin), Cyanidin-3-O-sambubioside[Cyanidin-3-O-(2″-O-xylosyl)glucoside], Cyanidin-3-O-glucoside (Kuromanin) and Cyanidin-3-O-(2″-O-xylosyl)rutinoside were identified as crucial anthocyanins in red currant. Transcriptomic data showed that the upregulation of dihydroflavonol 4-reductase (DFR), anthocyanin synthase (ANS), and UDP-glucose-flavonoid-3-O-glucosyltransferase (UFGT) genes significantly promoted the purple coloration of black currant fruit, while increased expression of Chalcone synthase (CHS) and flavonoid 3'-hydroxylase (F3'H) genes significantly intensified the red hue of red currant fruit. Furthermore, through weighted gene co-expression network analysis (WGCNA), we identified 11 transcription factors, including 3 bHLH, 2 MYB, 3 bZIP and 3 WRKY genes, which may serve as key regulators of anthocyanin biosynthesis. These findings provide a foundational understanding of the color dynamics in different currant varieties fruits throughout their developmental stages.PMID:39614491 | DOI:10.1016/j.foodres.2024.115056

Food Res Int. 2024 Nov;196:115048. doi: 10.1016/j.foodres.2024.115048. Epub 2024 Sep 14.ABSTRACTThe Large Yellow Croaker (LYC) with rich lipids offers numerous health benefits, yet its lipid profile remains underexplored. Therefore, the lipids of LYC were comprehensively profiled and compared based lipidomics. Higher nutritional value of LYC was identified based on lipid and fatty acid assessment, particularly ovary and brain. A total of 963 lipid species belonging to 47 lipid subclasses were identified, exhibiting higher levels of glycerophospholipids (GPs) and sphingolipids (SPs) in the brain, as well as high levels of glycolipids (GLs) in the muscle. Furthermore, unique lipid subclasses were detected in the brain (Acylcarnitine (CAR), Alpha-hydroxy-N-stearoyl phytosphingosine (Cer-AP)) and ovary (N-arachidonoyl glycine (NAGly)). Notably, 8 lipid subclasses were selected as potential contributors for four tissues differentiation. Additionally, identification of LYC from various origins was achieved through lipidomics for the first time. LYC from Zhejiang and Fujian provinces could be distinguished by 100 lipid biomarkers. Most different lipids significantly negatively correlated with seawater pH and dissolved oxygen, but positively correlated with netting density, depth, environmental temperature and salinity. This comprehensive analysis provided valuable insights into LYC's nutritional values and origin identified.PMID:39614487 | DOI:10.1016/j.foodres.2024.115048

Food Res Int. 2024 Nov;196:115034. doi: 10.1016/j.foodres.2024.115034. Epub 2024 Sep 3.ABSTRACTMetagenomics, non-targeted metabolomics, and metaproteomics were employed to analyze the microecological succession of high-temperature Daqu during storage, elucidate the adaptation mechanism of the microbial community of Daqu to storage environments, and clarify the microecological characteristics of Daqu during different seasons. During storage, the relative abundances of Bacillus, Oceanobacillus, Staphylococcus, and Aspergillus in Daqu had significantly increased, while those of Kroppenstedtia, Saccharopolyspora, Thermoascus, and Thermomyces had significantly decreased. During the first 3 months of storage, compound metabolism of Daqu was primarily dominated by generation of small molecular substances and then shifted to metabolism of amino sugars. During the storage process, homogeneous selection (15.57 %) and homogeneous diffusion (14.86 %) of the microbial communities of Daqu were much larger than during the fermentation process, while the variable selection assembly (29.43 %) was smaller than during the fermentation process. Among the 2509 proteins identified in the four-season Daqu, bacterial protein expression was 1.46-fold greater than that of fungi. Seasonal factors influenced the function of Daqu by alterations to Bacillus subtilis, Oceanobacillus iheyensis, and Aspergillus nidulans and other microbial functions. Carbon and benzoic acid metabolism of Daqu was relatively increased during the spring, while metabolism of alkaloids and tyrosine was upregulated during the summer, amino acid synthesis and starch metabolism were enriched during the autumn, and peptidoglycan synthesis was relatively greater during the winter. Adjusting the moisture content of Daqu during the storage period was shown to reduce microecological differentiation caused by seasonal temperature variations.PMID:39614477 | DOI:10.1016/j.foodres.2024.115034

Front Biosci (Landmark Ed). 2024 Nov 15;29(11):382. doi: 10.31083/j.fbl2911382.ABSTRACTBACKGROUND: Zophobas atratus larval meal (ZLM) is a high-quality feed supplement with potential activities that can improve fish growth performance and promote meat quality. However, there have been limited recent studies investigating the metabolic effects of ZLM. Therefore, this study aims to uncover the metabolomic mechanism through which ZLM improves tilapia meat flavor using metabolomic strategies.METHOD: In this study, soybean meal in the basal diets was replaced with 15%, 30%, or 60% ZLM, where anti-nutrient factors were destroyed by high temperature treatment. After being fed these ZLM supplements for 30 days, dorsal muscles were collected from tilapia for meat sensory evaluation tests. Liver samples were also collected for metabolomic analysis using the gas chromatography-mass spectrometry (GC-MS) platform and combined with biochemical assays to verify metabolism-related enzyme activities and reveal crucial metabolic pathways and critical biomarkers associated with ZLM's ability to improve meat flavor.RESULTS: In tilapia livers, ZLM enhanced the activity of enzymes involved in energy metabolism including succinate dehydrogenase (SDH), pyruvate dehydrogenase (PDH), α-ketoglutarate dehydrogenase (α-KGDH), NADP-malate dehydrogenase (NAD-MDH) and mitochondrial isocitrate dehydrogenase (ICDHm). This resulted in increased levels of reduced nicotinamide adenine dinucleotide (NADH), acetyl CoA and ATP which led to accumulation of flavor fatty acids such as arachidonic acid, linoleic acid (9,12-Octadecadienoic acid), linolenic acid (9,12,15-Octadecatrienoic acid) and oleic acid (9-Octadecenoic acid). Additionally, there was an increase in flavor nucleotides like guanosine adenosine-5'-monophosphate and uridine-5'-monophosphate while off-flavor metabolites like inosine and hypoxanthine decreased. Furthermore, beneficial metabolomic responses led to a decrease in off-flavor metabolites such as 2-methylisoborneol trimethylamine and geosmin while increasing umami metabolites like 2-methyl-3-furanthiol and nonanal.CONCLUSIONS: This metabolomic study demonstrates that inclusion of ZLM diets enhances the flavor profile of tilapia dorsal muscle. The accumulation of flavor compounds, coupled with a reduction in earthy taste and off-flavor metabolites, contributes to an improved meat flavor and freshness. Additionally, there is an increase in the levels of flavor-related amino acids and nucleotides. These previously unidentified metabolic effects highlight the potential significance of ZLM as a dietary supplement for enhancing the biosynthesis of flavor metabolites in tilapia.PMID:39614443 | DOI:10.31083/j.fbl2911382

Respir Res. 2024 Nov 29;25(1):421. doi: 10.1186/s12931-024-03050-3.ABSTRACTBACKGROUND: Microbial infections, particularly those caused by rhinovirus (RV) and respiratory syncytial virus (RSV), are major triggers for asthma exacerbations. These viruses activate toll-like receptors (TLRs), initiating an innate immune response. To better understand microbial-induced asthma exacerbations, animal models that closely mimic human lung characteristics are essential. This study aimed to assess airway responses in guinea pigs exposed to TLR agonists, simulating microbial infections.METHODS: The agonists poly(I: C) (TLR3), lipopolysaccharide (LPS; TLR4) and imiquimod (TLR7), or the combination of poly(I: C) and imiquimod (P/I) were administered intranasally once a day over four consecutive days. The latter group received daily intraperitoneal injections of dexamethasone starting one day before the TLR agonists challenge. Respiratory functions were measured by whole-body plethysmography and forced oscillatory technique. Bronchoalveolar lavage fluid (BALF) cells and lungs were collected for analysis.RESULTS: The intranasal exposure of LPS and P/I caused an increase in enhanced pause (Penh) after challenge, whereas neither poly(I: C) nor imiquimod alone showed any effect. After the challenges of LPS, poly(I: C) or P/I, but not imiquimod alone, induced an increase of both Rrs (resistance of the respiratory system) and Ers (elastance of the respiratory system). LPS exposure caused an increase of neutrophils in BALF, whereas none of the other exposures affected the composition of cells in BALF. Exposure to LPS, poly (I: C), imiquimod, and P/I all caused a marked infiltration of inflammatory cells and an increase of mast cells around the small airways. For the expression of inflammatory mediators, LPS increased CXCL8, poly(I: C) and imiquimod decreased IL-4 and IL-5, and increased IFNγ. Imiquimod increased CXCL8 and IL-6, whereas P/I decreased IL-5, and increased IL-6 and IFNγ. The increases in Rrs, Ers, and airway inflammation, but not the altered expression of inflammatory cytokines, were attenuated by dexamethasone.CONCLUSIONS: TLR agonists promote acute airway inflammation and induce airway obstruction and hyperresponsiveness in guinea pigs. The severity of these effects varies depending on the specific agonists used. Notably, dexamethasone reversed pulmonary functional changes and mitigated bronchial inflammation caused by the combined treatment of P/I. However, it had no impact on the expression of inflammatory mediators.PMID:39614276 | DOI:10.1186/s12931-024-03050-3

BMC Oral Health. 2024 Nov 29;24(1):1455. doi: 10.1186/s12903-024-05230-5.ABSTRACTBACKGROUND: Chronic apical periodontitis (CAP) has been linked to the development of atherosclerosis, although the underlying mechanisms remain unclear. This study aimed to investigate the role of gut microbiota disruption in CAP-induced atherosclerosis development, focusing on trimethylamine N-oxide (TMAO)-related metabolites.METHODS: The study utilized fecal microbiota transplantation (FMT) to transfer gut microbiota from mice with CAP to healthy mice. Atherosclerosis development was assessed by analyzing lesions in the aortic arch and aortic root. Serum lipid and inflammatory factor levels were measured. Composition and diversity of gut microbiota were analyzed using targeted metabolomics, with a focus on the ratio of Firmicutes to Bacteroidetes. The expression of hepatic flavin-containing monooxygenase 3 (FMO3) and serum TMAO levels were also evaluated.RESULTS: Mice receiving gut microbiota from CAP mice showed increased atherosclerotic lesions compared to controls, without significant differences in serum lipid or inflammatory factor levels. Alterations in gut microbiota composition were observed, characterized by an increase in the Firmicutes to Bacteroidetes ratio. Peptostreptococcaceae abundance positively correlated with atherosclerosis severity, while Odoribacteraceae showed a negative correlation. No significant differences were found in hepatic FMO3 expression or serum TMAO levels.CONCLUSIONS: The study confirms the role of gut microbiota disruption in CAP-mediated atherosclerosis development, independent of serum lipid or TMAO levels. Alterations in gut microbiota composition, particularly increased Firmicutes to Bacteroidetes ratio and specific bacterial families, were associated with atherosclerosis severity. These findings highlight the intricate interplay between gut microbiota and cardiovascular health in the context of CAP.PMID:39614243 | DOI:10.1186/s12903-024-05230-5

Sci Rep. 2024 Nov 29;14(1):29720. doi: 10.1038/s41598-024-80986-y.ABSTRACTProstate cancer (PCa) is the second most common malignancy affecting men globally. Recent advances in metabolomics have highlighted significant alterations in specific amino acid (AA) metabolism linked to PCa, indicating their potential utility in diagnosis and therapy. However, no direct causal association between serum AA levels and PCa risk has been established. A total of 35 patients with PCa and 30 individuals with benign prostatic hyperplasia (BPH) were recruited for this study. Targeted metabolomic analysis was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry on serum samples. Two-sample Mendelian randomization (MR) was applied to explore potential causal links between serum AA levels and PCa risk, including mediator effects using dual-phase MR and assessing reverse causality through reverse MR. Results Targeted metabolomic profiling identified six amino acids-glutamate (Glu), Ser, histidine (His), arginine (Arg), aspartic acid (Asp), and glycine (Gly)-that showed significant area under the ROC curve in differentiating between BPH and PCa cases. Notably, Glu demonstrated an inverse association with PCa risk, distinct from the other AAs identified. However, definitive evidence supporting a causal relationship between low Glu levels and increased PCa risk was not observed. Our results suggest a protective role of Glu against PCa development, which may have implications for disease prognosis. Increasing dietary Glu intake may present a potential preventive or therapeutic approach for PCa.PMID:39614073 | DOI:10.1038/s41598-024-80986-y

Insights Imaging. 2024 Nov 29;15(1):289. doi: 10.1186/s13244-024-01859-6.ABSTRACTOBJECTIVES: Gut-brain axis dysfunction has emerged as a key contributor to the pathogenesis of Crohn's disease (CD). The elucidation of neural alterations may provide novel insights into its management. We aimed to develop a multiparameter brain MRI-based radiomics model (RM) for characterizing neural alterations in CD patients and to interpret these alterations using multiomics traits.METHODS: This prospective study enrolled 230 CD patients and 46 healthy controls (HCs). Participants voluntarily underwent brain MRI and psychological assessment (n = 155), blood metabolomics analysis (n = 260), and/or fecal 16S rRNA sequencing (n = 182). The RM was developed using 13 features selected from 13,870 first-order features extracted from multiparameter brain MRI in training cohort (CD, n = 75; HCs, n = 32) and validated in test cohort (CD, n = 34; HCs, n = 14). Multiomics data (including gut microbiomics, blood metabolomics, and brain radiomics) were compared between CD patients and HCs.RESULTS: In the training cohort, area under the receiver operating characteristic curve (AUC) of RM for distinguishing CD patients from HCs was 0.991 (95% confidence interval (CI), 0.975-1.000). In test cohort, RM showed an AUC of 0.956 (95% CI, 0.881-1.000). CD-enriched blood metabolites such as triacylglycerol (TAG) exhibited significant correlations with both brain features detected by RM and CD-enriched microbiota (e.g., Veillonella). One notable correlation was found between Veillonella and Ctx-Lh-Middle-Temporal-CBF-p90 (r = 0.41). Mediation analysis further revealed that dysbiosis, such as of Veillonella, may regulate the blood flow in the middle temporal cortex through TAG.CONCLUSION: We developed a multiparameter MRI-based RM that characterized the neural alterations of CD patients, and multiomics data offer potential evidence to support the validity of our model. Our study may offer clues to help provide potential therapeutic targets.CRITICAL RELEVANCE STATEMENT: Our brain-gut axis study developed a novel model using multiparameter MRI and radiomics to characterize brain changes in patients with Crohn's disease. We validated this model's effectiveness using multiomics data, making it a potential biomarker for better patient management.KEY POINTS: Utilizing multiparametric MRI and radiomics techniques could unveil Crohn's disease's neurophenotype. The neurophenotype radiomics model is interpreted using multiomics data. This model may serve as a novel biomarker for Crohn's disease management.PMID:39613905 | DOI:10.1186/s13244-024-01859-6

Sci Rep. 2024 Nov 29;14(1):29737. doi: 10.1038/s41598-024-81005-w.ABSTRACTFruit color is a crucial trait for bell pepper. To investigate the mechanism of color formation, three bell pepper lines with different color (yellow, orange and red) were used as materials to conduct comprehensive targeted metabolomic and transcriptomic analyses. During the process of fruit development, 54 carotenoids metabolites were discovered, exhibiting unique accumulation patterns and notable variety specificity. The types and content of carotenoids in orange fruit (OM) were notably greater compared to the other two varieties. Red pigment (capsanthin and capsorubin) was specifically enriched in red fruit (RM), and yellow pigment (lutein and zeaxanthin) is the highest in yellow fruit (YM) and OM. Five modules positively correlated with carotenoid accumulation and one negative module was determined by weighted gene co-expression network analysis (WGCNA). Additionally, transcription factors (TFs) and hub genes related to carotenoid synthesis were predicted. By elucidating the regulation of 7 key carotenoid metabolites by 14 critical genes and 5 key TFs, we constructed a comprehensive carotenoid biosynthesis metabolic network that comprehensively explains the pigment changes observed in green and mature pepper fruit. Overall, the results not only provide important insights into carotenoid synthesis pathway, but also lay a solid base for revealing the mechanism of bell pepper color transformation.PMID:39613866 | DOI:10.1038/s41598-024-81005-w

Talanta. 2024 Nov 23;285:127280. doi: 10.1016/j.talanta.2024.127280. Online ahead of print.ABSTRACTCervical cancer (CC) remains a critical public health issue, highlighting the importance of early detection. However, current methods such as cytological and HPV testing face challenges of invasiveness and low patient compliance. Exosomes, emerging as crucial in cancer diagnosis, offer promise due to their noninvasive, highly specificity, and abundant biomarkers. However, isolating exosomes efficiently remains challenging. In this study, we designed and synthesized a bifunctional affinity nanomaterial Fe3O4 @CD63-CLIKKPF, based on the synergistic interaction between its modified aptamer CD63 and peptide CLIKKPF, and CD63 protein and PS of exosomes which can achieve high specificity and high yield separation of urinary exosomes. Notably, the co-modified aptamer CD63 and peptide CLIKKPF not only enable efficient exosome isolation by leveraging dual-affinity mechanisms through a synergistic "AND" logic analysis, but also could be achieved on the Fe3O4 in one-step reaction at room temperature via Fe-S bonding. Combined with LC-MS/MS, we conducted exosome metabolomics analysis in healthy individuals and CC patients across various stages, and machine learning models demonstrated accurate classification (accuracy >0.822) and prediction capabilities for CC. Furthermore, six key metabolites indicative of CC progression were identified and validated in additional patient samples, highlighting their potential as biomarkers. Overall, this study establishes a novel method for exosome metabolomics in CC, offering insights for non-invasive early diagnosis and progression prediction on a large scale.PMID:39613490 | DOI:10.1016/j.talanta.2024.127280

Reprod Toxicol. 2024 Nov 27:108758. doi: 10.1016/j.reprotox.2024.108758. Online ahead of print.ABSTRACTDi-(2-ethylhexyl) phthalate (DEHP) exposure has been associated with male reproductive damage, but the mechanisms involved remain incompletely defined. This study aims to investigate the effects of DEHP exposure on the testes of prepubertal rats through an integrative analysis of metabolomics and transcriptomics, combined with molecular experiments. DEHP exposure resulted in decreased testis weight and increased oxidative stress level in the testis tissues of prepubertal male rats. Moreover, our findings showed a disordered testis structure, reduced spermatogenic and Sertoli cells as well as destruction of mitochondria structure in the testis tissues of DEHP-treated prepubertal male rats. Transcriptome function analysis together with metabolome function analysis indicated that spermatogenesis, apoptosis, inflammatory, lipid metabolism as well as DNA repair signaling pathway were enriched in the testis of DEHP-treated prepubertal male rats. The integrative omics analysis further suggested that TNF-α induced apoptosis played a crucial role in mediating the detrimental effects of DEHP exposure on the testis of prepubertal rats, which was validated by ELISA, Western blotting and Tunel assays. Validation experiments conducted in vitro using GC-2 cells corroborated these findings, demonstrating that mono-(2-ethylhexyl) phthalate (MEHP), the main active metabolite of DEHP, significantly inhibits cell proliferation and increases apoptosis via activating the TNF-α apoptosis pathway. Overall, these findings provided a novel mechanism of dysregulated spermatogenesis of DEHP exposure on the testes of prepubertal rats.PMID:39613166 | DOI:10.1016/j.reprotox.2024.108758

J Ethnopharmacol. 2024 Nov 27:119158. doi: 10.1016/j.jep.2024.119158. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: The current treatment for diabetic nephropathy (DN) is inadequate, and there is an urgent need for an effective and minimally adverse alternative therapy. Da-Chai-Hu Decoction (DCHD) is a time-honored herbal remedy from Chinese medicine, boasting a legacy spanning more than 1800 years. Clinical observations suggest that it may provide therapeutic benefits for individuals with type 2 diabetes mellitus (T2DM). Nonetheless, the specific advantages of DCHD in relation to diabetic nephropathy (DN) and the mechanisms through which it operates are still not well understood.AIM OF THE STUDY: This research aims to investigate whether DCHD can avert renal damage in mice with T2DM and to elucidate the mechanisms by which DCHD combats DN through the integration of metabolomics and network pharmacology.MATERIALS AND METHODS: The beneficial effects of DCHD on DN was initially evaluated using a renal injury model in T2DM mice. Subsequently, untargeted metabolomics analysis was utilized to investigate the potential mechanisms of DCHD against DN. Additionally, UPLC-MS/MS was employed to identify the chemical components in DCHD and the absorption components in DCHD-treated plasma. Network pharmacology and our newly proposed function-guided and network-based complementary methodology (FNICM) was utilized to predict the potential pathway of DCHD intervention in DN. Finally, the core pathway was validated through Western blotting analysis and ELISA.RESULTS: A total of 260 chemical components were detected in DCHD, and 41 absorption components were found in DCHD-treated plasma by UPLC-HR MS/MS for the first time. Additionally, In vivo experiments revealed that DCHD exerts the ability to regulate the disorder in glucose/lipid metabolism and improves kidney dysfunction. Furthermore, a comprehensive analysis utilizing non-targeted urine metabolomics and the FNICM method identified a total of 33 differential metabolites, which were categorized as core metabolites. Lastly, combined FNICM, network pharmacology and experimental pharmacology studies suggest that DCHD may regulate the AGEs/RAGE/AKT pathways in combating DN.CONCLUSIONS: The results indicate that DCHD treats DN through the inhibition of the AGEs/RAGE/AKT pathway and by regulating metabolic profiles.PMID:39613006 | DOI:10.1016/j.jep.2024.119158

Biochim Biophys Acta Mol Basis Dis. 2024 Nov 27:167567. doi: 10.1016/j.bbadis.2024.167567. Online ahead of print.ABSTRACTIt becomes increasingly clear that the tissue specificity of mitochondrial diseases might in part rely on their ability to compensate for mitochondrial defects, contributing to the heterogeneous nature of mitochondrial diseases. Here, we investigated tissue-specific responses to cytochrome c oxidase (CIV or COX) deficiency using a mouse model with heart and skeletal muscle-specific depletion of the COX assembly factor COX10. At three weeks of age, both tissues exhibit pronounced CIV depletion but respond differently to oxidative phosphorylation (OXPHOS) impairment. Heart-specific COX10 depletion caused severe dilated cardiomyopathy, while skeletal muscle experiences less damage. Cardiac CIV deficiency triggered extensive metabolic remodelling and stress response activation, potentially worsening cardiomyopathy, whereas skeletal muscle showed no stress response or significant metabolic changes. Our findings highlight distinct tissue capacities for managing CIV deficiency, explaining how identical primary defects can lead to different phenotypic outcomes and contribute to the heterogeneous progression of mitochondrial diseases.PMID:39613003 | DOI:10.1016/j.bbadis.2024.167567