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

Engineering Climate-Resilient Rice Using a Nanobiostimulant-Based "Stress Training" Strategy

Wed, 31/05/2023 - 12:00
ACS Nano. 2023 May 31. doi: 10.1021/acsnano.3c02215. Online ahead of print.ABSTRACTUnder a changing climate, cultivating climate-resilient crops will be critical to maintaining food security. Here, we propose the application of reactive oxygen species (ROS)-generating nanoparticles as nanobiostimulants to trigger stress/immune responses and subsequently increase the stress resilience of plants. We established three regimens of silver nanoparticles (AgNPs)-based "stress training": seed training (ST), leaf training (LT), and combined seed and leaf training (SLT). Trained rice seedlings were then exposed to either rice blast fungus (Magnaporthe oryzae) or chilling stress (10 °C). The results show that all "stress training" regimes, particularly SLT, significantly enhanced the resistance of rice against the fungal pathogen (lesion size reduced by 82% relative to untrained control). SLT also significantly enhanced rice tolerance to cold stress. The mechanisms for the enhanced resilience were investigated with metabolomics and transcriptomics, which show that "stress training" induced considerable metabolic and transcriptional reprogramming in rice leaves. AgNPs boosted ROS-activated stress signaling pathways by oxidative post-translational modifications of stress-related kinases, hormones, and transcriptional factors (TFs). These signaling pathways subsequently modulated the expression of defense genes, including specialized metabolites (SMs) biosynthesis genes, cell membrane lipid metabolism genes, and pathogen-plant interaction genes. Importantly, results showed that the "stress memory" can be transferred transgenerationally, conferring offspring seeds with improved seed germination and seedling vigor. This may provide an epigenetic breeding strategy to fortify stress resilience of crops. This nanobiostimulant-based stress training strategy will increase yield vigor against a changing climate and will contribute to sustainable agriculture by reducing agrochemical use.PMID:37256700 | DOI:10.1021/acsnano.3c02215

Metabolomic profiling of bacterial biofilm: trends, challenges, and an emerging antibiofilm target

Wed, 31/05/2023 - 12:00
World J Microbiol Biotechnol. 2023 May 31;39(8):212. doi: 10.1007/s11274-023-03651-y.ABSTRACTBiofilm-related infections substantially contribute to bacterial illnesses, with estimates indicating that at least 80% of such diseases are linked to biofilms. Biofilms exhibit unique metabolic patterns that set them apart from their planktonic counterparts, resulting in significant metabolic reprogramming during biofilm formation. Differential glycolytic enzymes suggest that central metabolic processes are markedly different in biofilms and planktonic cells. The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is highly expressed in Staphylococcus aureus biofilm progenitors, indicating that changes in glycolysis activity play a role in biofilm development. Notably, an important consideration is a correlation between elevated cyclic di-guanylate monophosphate (c-di-GMP) activity and biofilm formation in various bacteria. C-di-GMP plays a critical role in maintaining the persistence of Pseudomonas aeruginosa biofilms by regulating alginate production, a significant biofilm matrix component. Furthermore, it has been demonstrated that S. aureus biofilm development is initiated by several tricarboxylic acid (TCA) intermediates in a FnbA-dependent manner. Finally, Glucose 6-phosphatase (G6P) boosts the phosphorylation of histidine-containing protein (HPr) by increasing the activity of HPr kinase, enhancing its interaction with CcpA, and resulting in biofilm development through polysaccharide intercellular adhesion (PIA) accumulation and icaADBC transcription. Therefore, studying the metabolic changes associated with biofilm development is crucial for understanding the complex mechanisms involved in biofilm formation and identifying potential targets for intervention. Accordingly, this review aims to provide a comprehensive overview of recent advances in metabolomic profiling of biofilms, including emerging trends, prevailing challenges, and the identification of potential targets for anti-biofilm strategies.PMID:37256458 | DOI:10.1007/s11274-023-03651-y

Integrated transcriptome and metabolome analysis to investigate the mechanism of intranasal insulin treatment in a rat model of vascular dementia

Wed, 31/05/2023 - 12:00
Front Pharmacol. 2023 May 15;14:1182803. doi: 10.3389/fphar.2023.1182803. eCollection 2023.ABSTRACTIntroduction: Insulin has an effect on neurodegenerative diseases. However, the role and mechanism of insulin in vascular dementia (VD) and its underlying mechanism are unknown. In this study, we aimed to investigate the effects and mechanism of insulin on VD. Methods: Experimental rats were randomly assigned to control (CK), Sham, VD, and insulin (INS) + VD groups. Insulin was administered by intranasal spray. Cognitive function was evaluated using the Morris's water maze. Nissl's staining and immunohistochemical staining were used to assess morphological alterations. Apoptosis was evaluated using TUNEL-staining. Transcriptome and metabolome analyses were performed to identify differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs), respectively. Results: Insulin significantly improved cognitive and memory functions in VD model rats (p < 0.05). Compared with the VD group, the insulin + VD group exhibited significantly reduced the number of Nissl's bodies numbers, apoptosis level, GFAP-positive cell numbers, apoptosis rates, and p-tau and tau levels in the hippocampal CA1 region (p < 0.05). Transcriptomic analysis found 1,257 and 938 DEGs in the VD vs. CK and insulin + VD vs. VD comparisons, respectively. The DEGs were mainly enriched in calcium signaling, cAMP signaling, axon guidance, and glutamatergic synapse signaling pathways. In addition, metabolomic analysis identified 1 and 14 DEMs between groups in negative and positive modes, respectively. KEGG pathway analysis indicated that DEGs and DEMs were mostly enriched in metabolic pathway. Conclusion: Insulin could effectively improve cognitive function in VD model rats by downregulating tau and p-tau expression, inhibiting astrocyte inflammation and neuron apoptosis, and regulating genes involved in calcium signaling, cAMP signaling, axon guidance, and glutamatergic synapse pathways, as well as metabolites involved in metabolic pathway.PMID:37256231 | PMC:PMC10225696 | DOI:10.3389/fphar.2023.1182803

The Metabolism of Susceptibility: Clearing the FoG Between Tolerance and Resistance in <em>Candida albicans</em>

Wed, 31/05/2023 - 12:00
Curr Clin Microbiol Rep. 2023 Mar 28;10(2):36-46. doi: 10.1007/s40588-023-00189-3.ABSTRACTPURPOSE OF REVIEW: Failure of antifungal treatment is alarmingly common in patients infected with Candida albicans isolates that test as susceptible in vitro. This means that clinical susceptibility tests have limited predictive value for treatment success. To guide the improvement of patient outcomes, we must understand the effects of environmental and metabolic states on drug responses.RECENT FINDINGS: Lab conditions often deviate from host environments, and current susceptibility testing standards ignore slow-growing, tolerant phenotypes; both factors may contribute to antifungal treatment failure. Metabolomic studies reveal that strain background, nutrient availability, and drug exposure influence the metabolic state of C. albicans cells; similarly, the metabolic state influences drug susceptibility.SUMMARY: Identifying tolerant strains in the clinic may improve patient outcomes. Studies that analyze the effects of essential but limited nutrients have the potential to improve the avoidance of persistent candidiasis and to reduce the frequency of antifungal treatment failures. Here, we highlight literature that explores the effect of drug exposure and antifungal drug resistance status on the C. albicans metabolome. Similar analyses need to be carried out relative to antifungal drug tolerance. Additionally, we focus on the biological relevance of four essential small molecules-iron, zinc, phosphate, and sphingolipids-to antifungal tolerance and resistance.PMID:37256197 | PMC:PMC7614596 | DOI:10.1007/s40588-023-00189-3

LC-MS based urine untargeted metabolomic analyses to identify and subdivide urothelial cancer

Wed, 31/05/2023 - 12:00
Front Oncol. 2023 May 12;13:1160965. doi: 10.3389/fonc.2023.1160965. eCollection 2023.ABSTRACTINTRODUCTION: Urine metabolomics has been a promising technique in the liquid biopsy of urothelial cancer (UC). The comparison of upper tract urothelial cancer (UTUC), lower tract urothelial cancer (BCa), and healthy controls (HCs) need to be performed to find related biomarkers.METHODS: In our investigation, urine samples from 35 UTUCs, 44 BCas, and 53 gender- and age-matched HCs were analyzed using liquid chromatography-high resolution mass spectrometry (LC-HRMS). In different groups, the differential metabolites and the disturbed metabolism pathways were explored. Transcriptomics and urine metabolomics are combined to identify the probably disturbed gene in BCa.RESULTS: With an area under the curve (AUC) of 0.815, the panel consisting of prostaglandin I2, 5-methyldeoxycytidine, 2,6-dimethylheptanoyl carnitine, and deoxyinosine was able to discriminate UC from HCs. With an AUC of 0.845, the validation group also demonstrated strong predictive ability. UTUC and BCa without hematuria could be distinguished using the panel of 5'-methylthioadenosine, L-beta-aspartyl-L-serine, dehydroepiandrosterone sulfate, and N'-formylkynurenine (AUC=0.858). The metabolite panel comprising aspartyl-methionine, 7-methylinosine, and alpha-CEHC glucuronide could discriminate UTUC from BCa with hematuria with an AUC of 0.83. Fatty acid biosynthesis, purine metabolism, tryptophan metabolism, pentose and glucuronate interconversions, and arachidonic acid metabolism were dysregulated when comparing UC with HCs. PTGIS and BCHE, the genes related to the metabolism of prostaglandin I2 and myristic acid respectively, were significantly associated with the survival of BCa.DISCUSSION: Not only could LC-HRMS urine metabolomic investigations distinguish UC from HCs, but they could also identify UTUC from BCa. Additionally, urine metabolomics combined with transcriptomics can find out the potential aberrant genes in the metabolism.PMID:37256175 | PMC:PMC10226587 | DOI:10.3389/fonc.2023.1160965

Calorie restriction and pravastatin administration during pregnancy in obese rhesus macaques modulates maternal and infant metabolism and infant brain and behavioral development

Wed, 31/05/2023 - 12:00
Front Nutr. 2023 May 15;10:1146804. doi: 10.3389/fnut.2023.1146804. eCollection 2023.ABSTRACTBACKGROUND: Maternal obesity has been associated with a higher risk of pregnancy-related complications in mothers and offspring; however, effective interventions have not yet been developed. We tested two interventions, calorie restriction and pravastatin administration, during pregnancy in a rhesus macaque model with the hypothesis that these interventions would normalize metabolic dysregulation in pregnant mothers leading to an improvement in infant metabolic and cognitive/social development.METHODS: A total of 19 obese mothers were assigned to either one of the two intervention groups (n = 5 for calorie restriction; n = 7 for pravastatin) or an obese control group (n = 7) with no intervention, and maternal gestational samples and postnatal infant samples were compared with lean control mothers (n = 6) using metabolomics methods.RESULTS: Gestational calorie restriction normalized one-carbon metabolism dysregulation in obese mothers, but altered energy metabolism in her offspring. Although administration of pravastatin during pregnancy tended to normalize blood cholesterol in the mothers, it potentially impacted the gut microbiome and kidney function of their offspring. In the offspring, both calorie restriction and pravastatin administration during pregnancy tended to normalize the activity of AMPK in the brain at 6 months, and while results of the Visual Paired-Comparison test, which measures infant recognition memory, was not significantly impacted by either of the interventions, gestational pravastatin administration, but not calorie restriction, tended to normalize anxiety assessed by the Human Intruder test.CONCLUSIONS: Although the two interventions tested in a non-human primate model led to some improvements in metabolism and/or infant brain development, negative impacts were also found in both mothers and infants. Our study emphasizes the importance of assessing gestational interventions for maternal obesity on both maternal and offspring long-term outcomes.PMID:37255938 | PMC:PMC10225656 | DOI:10.3389/fnut.2023.1146804

Association of ABCC8 gene variants with response to sulfonylurea in type 2 diabetes mellitus

Wed, 31/05/2023 - 12:00
J Diabetes Metab Disord. 2023 Jan 28;22(1):649-655. doi: 10.1007/s40200-023-01189-2. eCollection 2023 Jun.ABSTRACTBACKGROUND: Diabetes mellitus (DM) is associated with high blood glucose levels and sulfonylureas (SFUs) are one of the treatment options for DM. SFUs bind to sulfonylurea-1 receptor (SUR1), which is encoded by the ABCC8 gene and leads to blood glucose reduction. Genetic variants like rs757110 and rs1799854 of ABCC8 can influence the response to the drug's efficiency. Therefore, this study aimed to investigate the association between the ABCC8 rs757110 and rs1799854 genetic variants and response to SFUs treatment.METHODS: Totally, 61 DM patients with SFUs treatment were included. Baseline characteristics of the patients were recorded and 5 ml of blood was taken from each patient. After DNA extraction, a sequence containing rs757110 and rs1799854 was synthesized by the PCR method, and the PCR products were used for Sanger sequencing.RESULTS: Frequencies of GG, GA, and AA genotypes of rs1799854 variant was 12 (40%), 14 (46.7%), and 4 (13.3%), and the frequencies of CC, AC, and AA genotypes for rs757110 variant was 3 (9.7%), 5 (16.1%) and 23 (74.2%) in, respectively. Patients with different genotypes had the same age, BMI (body mass index), initial FBS (Fasting blood sugar), initial HbA1c, treatment duration, gender and history of smoking, alcohol consumption, and exercise. There was no significant difference in FBS and HbA1c changes after SFUs treatment between patients with rs757110 variant (p = 0.39 for FBS and p = 0.76 for HbA1c) and rs1799854 (p = 0.24 for FBS and p = 0.36 for HbA1c).CONCLUSION: The rs1799854 and rs757110 variants of the ABCC8 gene had no significant influence on response to SFUs treatment.PMID:37255830 | PMC:PMC10225415 | DOI:10.1007/s40200-023-01189-2

Exploring human biology with N-of-1 clinical trials

Wed, 31/05/2023 - 12:00
Camb Prism Precis Med. 2023;1:e12. doi: 10.1017/pcm.2022.15. Epub 2023 Jan 10.ABSTRACTStudies on humans that exploit contemporary data-intensive, high-throughput 'omic' assay technologies, such as genomics, transcriptomics, proteomics and metabolomics, have unequivocally revealed that humans differ greatly at the molecular level. These differences, which are compounded by each individual's distinct behavioral and environmental exposures, impact individual responses to health interventions such as diet and drugs. Questions about the best way to tailor health interventions to individuals based on their nuanced genomic, physiologic, behavioral, etc. profiles have motivated the current emphasis on 'precision' medicine. This review's purpose is to describe how the design and execution of N-of-1 (or personalized) multivariate clinical trials can advance the field. Such trials focus on individual responses to health interventions from a whole-person perspective, leverage emerging health monitoring technologies, and can be used to address the most relevant questions in the precision medicine era. This includes how to validate biomarkers that may indicate appropriate activity of an intervention as well as how to identify likely beneficial interventions for an individual. We also argue that multivariate N-of-1 and aggregated N-of-1 trials are ideal vehicles for advancing biomedical and translational science in the precision medicine era since the insights gained from them can not only shed light on how to treat or prevent diseases generally, but also provide insight into how to provide real-time care to the very individuals who are seeking attention for their health concerns in the first place.PMID:37255593 | PMC:PMC10228692 | DOI:10.1017/pcm.2022.15

Adverse events after the transjugular intrahepatic portal shunt are linked to serum metabolomic changes following the procedure

Wed, 31/05/2023 - 12:00
Front Mol Biosci. 2023 May 15;10:1168782. doi: 10.3389/fmolb.2023.1168782. eCollection 2023.ABSTRACTBackground and Objective: Transjugular intrahepatic portal shunt (TIPS) insertion could promote weight gain and muscle and fat mass increase in patients with cirrhosis. However, few studies have focused on metabolic changes after TIPS. This study aims to explore metabolic changes after TIPS and potential biomarkers of adverse events. Methods: Peripheral and portal serum samples were collected before and after TIPS insertion. Untargeted metabolomics was performed using ultra-high-performance liquid chromatography-mass spectrometry. Spearman's correlation analysis was used to determine the relationship between metabolites and clinical parameters. Metabolite set enrichment analysis was performed to explore enriched pathways. The predictive value of the metabolites was calculated by receiver operating characteristic curve (ROC) analysis. Results: Metabolites in the peripheral and portal serum significantly changed early after TIPS. Some lipid metabolites were significantly correlated with liver function parameters. Both elevated and depleted metabolites were mainly enriched in amino acid metabolism. Nine and 12 portal metabolites have moderate predictive value in post-TIPS liver function decline and hepatic encephalopathy (HE), separately (area under curve >0.7). Conclusion: Metabolites in the peripheral and portal veins significantly changed after TIPS. Some metabolic changes might be ascribed to liver function decline early after TIPS. Nine and 12 portal metabolites might be potential biomarkers in prediction of liver function decline and HE, separately.PMID:37255539 | PMC:PMC10225654 | DOI:10.3389/fmolb.2023.1168782

Pancreatic tumors exhibit myeloid-driven amino acid stress and upregulate arginine biosynthesis

Wed, 31/05/2023 - 12:00
Elife. 2023 May 31;12:e81289. doi: 10.7554/eLife.81289. Online ahead of print.ABSTRACTNutrient stress in the tumor microenvironment requires cancer cells to adopt adaptive metabolic programs for survival and proliferation. Therefore, knowledge of microenvironmental nutrient levels and how cancer cells cope with such nutrition is critical to understand the metabolism underpinning cancer cell biology. Previously, we performed quantitative metabolomics of the interstitial fluid (the local perfusate) of murine pancreatic ductal adenocarcinoma (PDAC) tumors to comprehensively characterize nutrient availability in the microenvironment of these tumors (M. R. Sullivan, Danai, et al., 2019). Here, we develop Tumor Interstitial Fluid Medium (TIFM), a cell culture medium that contains nutrient levels representative of the PDAC microenvironment, enabling us to study PDAC metabolism ex vivo under physiological nutrient conditions. We show that PDAC cells cultured in TIFM adopt a cellular state closer to that of PDAC cells present in tumors compared to standard culture models. Further, using the TIFM model, we found arginine biosynthesis is active in PDAC and allows PDAC cells to maintain levels of this amino acid despite microenvironmental arginine depletion. We also show that myeloid derived arginase activity is largely responsible for the low levels of arginine in PDAC tumors. Altogether, these data indicate that nutrient availability in tumors is an important determinant of cancer cell metabolism and behavior, and cell culture models that incorporate physiological nutrient availability have improved fidelity to in vivo systems and enable the discovery of novel cancer metabolic phenotypes.PMID:37254839 | DOI:10.7554/eLife.81289

Mass spectrometry-based metabolic profiling for identification of biomarkers related to footpad dermatitis in ducks

Wed, 31/05/2023 - 12:00
Br Poult Sci. 2023 May 31. doi: 10.1080/00071668.2023.2214884. Online ahead of print.ABSTRACT1. A new assessment method for duck footpad dermatitis (FPD) evaluation was developed, combining visual and histological characters using the images and sections of 400 ducks' feet at 340 d of age. All ducks were graded as G0 (healthy), G1 (mild), G2 (moderate) and G3 (severe) according to the degree of FPD.2. To reveal the potential biomarkers in serum related to duck FPD, non-targeted metabolomics and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to explore differential metabolites in each group.3. There were 57, 91 and 210 annotated differential metabolites in groups G1, G2 and G3 compared with G0, which meant that the severity of FPD increasedin line with the number of metabolites. Four metabolites, L-phenylalanine, L-arginine, L-leucine and L-lysine, were considered potential biomarkers related to FPD.4. KEGG enrichment analysis showed that the FPD was mainly involved in glycolysis, the tricarboxylic acid (TCA) cycle, the pentose phosphate pathway and amino acid metabolism. These are related to production metabolism and can affect the physiological activities of ducks, which might explain the decrease in production performance.PMID:37254666 | DOI:10.1080/00071668.2023.2214884

A Pilot Controlled Feeding Trial Modifying Protein Intake in Healthy Subjects to Assess Adherence and the Metabolome

Wed, 31/05/2023 - 12:00
Nutr Cancer. 2023 May 30:1-12. doi: 10.1080/01635581.2023.2217542. Online ahead of print.ABSTRACTDietary protein has been shown to impact physiology and pathophysiology, including inflammation and cancer, effects believed to occur through host and microbe-mediated mechanisms. However, the majority of studies investigating this concept have been conducted in animal models, with less information on the optimal approach, tolerability and biologic effects of modifying protein intake in humans. The current study presents a longitudinal controlled feeding trial carried out in healthy humans to acutely modulate protein intake using individualized diets. Adherence to study diets was monitored through subject-reported electronic picture-based assessments and global metabolomic analysis was performed on serum and stool, following each diet stage. Subjects exhibited strong adherence to study diets, with macronutrient intake meeting study goals during each stage. Metabolomic analysis revealed shifts in both serum and feces in association with modifying protein intake, including reciprocal changes in the abundance of amino acids and amino-acid related compounds, when comparing high to reduced protein stages. Additional fecal metabolite changes consisted of reduced microbial fermentation products following the reduced protein diet stage. Collectively, this study provides a robust method to precisely modify and monitor protein intake in humans, as well as assess corresponding metabolomic alterations.PMID:37254527 | DOI:10.1080/01635581.2023.2217542

PLU1 Promotes the Proliferation and Migration of Glioma Cells and Regulates Metabolism

Wed, 31/05/2023 - 12:00
Technol Cancer Res Treat. 2023 Jan-Dec;22:15330338231175768. doi: 10.1177/15330338231175768.ABSTRACTOBJECTIVES: PLU1 is upregulated in many cancers, including breast, mammary, colorectal, and hepatocellular carcinoma. However, little is known about the potential metabolic mechanisms of PLU1 in glioma progression. Therefore, we investigated the relationship between PLU1 and glioma development.METHODS: We analyzed the relationship between PLU1 expression and World Health Organization (WHO) grade using clinical databases and verified the role of PLU1 in glioma development using transcriptome sequencing, Western blotting, Cell Counting Kit 8, colony formation, and wound healing assays. The relationship between PLU1 and glioma glucose metabolism was also initially explored by changing the concentration of glucose in the culture medium and was validated by metabolomics and energy metabolism.RESULT: PLU1 expression was closely related to WHO grade and was significantly elevated in tumor tissues compared to nontumor tissues. Knockdown or inhibition of PLU1 inhibits proliferation and migration of glioma cells. In addition, we found that PLU1 expression was closely associated with glioma metabolism by transcriptomic, metabolomic, and energy-related molecular analyses and correlated with glucose metabolism. We also found that glucose concentration affects PLU1 expression, and that PLU1 expression affects intracellular glucose levels.CONCLUSION: PLU1 is a novel regulator of metabolic reprograming and a novel strategy for the treatment of glioma.PMID:37254514 | DOI:10.1177/15330338231175768

Integrated transcriptomic and metabolomic analysis of chili pepper fruits provides new insight into the regulation of the branched chain esters and capsaicin biosynthesis

Wed, 31/05/2023 - 12:00
Food Res Int. 2023 Jul;169:112856. doi: 10.1016/j.foodres.2023.112856. Epub 2023 Apr 28.ABSTRACTChili pepper (Capsicum spp.) is one of the world's most popular vegetables and spices. Aroma is an important quality indicator of pepper, but the nature of the related volatiles is still not clear. In this study, we investigated the fruit of two pepper varieties, one with strong fruity aroma 'CC' Capsicum chinense and one without 'TJ' Capsicum annuum at four different developmental stages using transcriptomic and metabolomic analysis. The results showed that the content of green leaf volatiles (GLVs) was higher in TJ than in CC and was higher in the young fruit stage in both varieties. GLVs content was positively correlated with the expression of 13-LOX1, 2, 5 and HPL. But the levels of branched-chain (BC) esters and capsaicin were higher in CC, and were positively correlated with the expression of IMPS4 and DADH1. Our findings shed light on the molecular mechanism of aroma biosynthesis in pepper and provide a theoretical basis for the molecular breeding of high-quality pepper fruits.PMID:37254430 | DOI:10.1016/j.foodres.2023.112856

Identification of colupulone and lupulone as the main contributors to the antibacterial activity of hop extracts using activity-guided fractionation and metabolome analysis

Wed, 31/05/2023 - 12:00
Food Res Int. 2023 Jul;169:112832. doi: 10.1016/j.foodres.2023.112832. Epub 2023 Apr 17.ABSTRACTHop is widely used in beer brewing and as a medicinal product. The present study comprehensively analyzed the main molecular determinants of the antibacterial activity of hop extracts. Minimum inhibitory concentrations (MIC) against Bacillus subtilis between 31.25 and 250 µg/mL were found in the ethanolic extracts of five hop varieties for beer brewing, but not in the tea hop sample. Activity-guided fractionation revealed the highest antibacterial activity for lupulone and adlupulone (MIC 0.98 µg/mL). Metabolome profiling and subsequent multistep statistical analysis detected 33 metabolites out of 1826 features to be associated with the antibacterial activity including humulone, adhumulone, colupulone, lupulone, and adlupulone. Xanthohumol, the three humulone- and three lupulone congeners were quantified in the hop extracts by a validated ultrahigh-performance liquid chromatography-mass spectrometry method. Considering concentrations and MICs, colupulone and lupulone were identified as major contributors to the antibacterial activity of hop extract with the highest antibacterial activity values (concentration/MIC) of 1.59 and 2.56.PMID:37254407 | DOI:10.1016/j.foodres.2023.112832

Lipids and volatile organic compounds in sesame seeds and their relationships with environmental temperature-induced stress

Wed, 31/05/2023 - 12:00
Food Res Int. 2023 Jul;169:112831. doi: 10.1016/j.foodres.2023.112831. Epub 2023 Apr 17.ABSTRACTSesame seeds contain several lipids and fragrances that offer health benefits. However, no studies have reported a relationship between the lipids or flavor compounds of sesame seeds and environmental factors. In this study, we aimed to identify this relationship by analyzing the contents of lipidic and flavor compounds in fifteen genotypes of sesame seeds grown in two cultivation regions (Jeonju and Miryang) and years (2018 and 2019). Herein, 17 lipids and 62 flavor compounds were detected. Multivariate statistical analyses revealed that the cultivation year had a larger influence on the contents of lipidic and flavor compounds than the cultivation region and genotype. Furthermore, heat stress due to high cultivation temperature in 2018 caused the accumulation of sugar and secondary metabolites, increased flavor-related substances, and inhibited the degradation of fatty acids. Our study is the first to demonstrate the metabolic changes in lipids and flavor components of sesame in response to environmental temperature changes affected by different cultivation years. Therefore, this study provides guidance for the cultivation of commercially advantageous sesame seeds in improving the quality of sesame seeds and their products.PMID:37254406 | DOI:10.1016/j.foodres.2023.112831

Quantitative metabolomic analysis reveals the fractionation of active compounds during lemon fruit juicing

Wed, 31/05/2023 - 12:00
Food Res Int. 2023 Jul;169:112829. doi: 10.1016/j.foodres.2023.112829. Epub 2023 Apr 17.ABSTRACTIn this study, metabolomic analysis was employed to investigate the separation (fractionation) of active compounds into lemon juice (LJ) and lemon pomace (LP) during lemon juicing. A total of 968 metabolites were identified, and 438 differentially abundant metabolites (DAMs) were screened out between LJ and LP, suggesting significant metabolite fractionation during juicing. The "flavonoids", "phenolic acids", and "saccharides and alcohols" were mainly retained in the LP, while the fractionation of major "organic acids" was differentiated. Seven of the 12 potential bitter metabolites were more abundant in the LP and two were more abundant in the LJ, suggesting that LP would be more bitter. L-Ascorbic acid, thiamine, and acitretin were significantly lost during juicing, while riboflavin was newly dissolved during juicing. The antioxidant capacity of LP was significantly higher than that of LJ, which was closely related to the higher abundance of phenolic acid metabolites in LP. These findings suggtested that promoting the release of flavonoids and phenolic acids from LP is a potential strategy to improve the quality of LJ. Results also provides important information and reference for developing high-value products by using LP.PMID:37254405 | DOI:10.1016/j.foodres.2023.112829

Effect of extrusion temperature on characteristic amino acids, fatty acids, organic acids, and phenolics of white quinoa based on metabolomics

Wed, 31/05/2023 - 12:00
Food Res Int. 2023 Jul;169:112761. doi: 10.1016/j.foodres.2023.112761. Epub 2023 Mar 31.ABSTRACTQuinoa is considered a "full nutritional food" owing to its high nutrition value. However, the whole grain form of quinoa is not always convenient direct consumption in everyday life. Extrusion is effective viable solution to this issue. In this study, the metabolic characterization of white quinoa (WQ) and extruded white quinoa (EWQ) was performed by investigating the characteristic amino acids, fatty acids, organic acids, and phenolic content of WQ after extrusion. A total of 24 amino acids, 25 organic acids, 32 fatty acids and 50 phenolics were identified in both WQ and EWQ, The results showed that extrusion and extrusion temperature significantly (p < 0.05) affect the content of amino acids, fatty acids, organic acids and phenolics in WQ. For example, the content of glutaconic acid (1231.9 μg/g of EWQ-180 to 1926.4 μg/g of WQ) and L-aspartic acid (115.47 μg/g of EWQ-140 to 643.70 μg/g of WQ) in WQ was significantly decreased, while L-serine (138.01 μg/g of WQ to 201.04 μg/g of EWQ-160) was increased respectively after extrusion. Among the EWQ samples, the highest content of glutaconic acid (1447.9 μg/g), L-aspartic acid (270.32 μg/g), and L-serine (201.04 μg/g) was observed in EWQ-160, EWQ-180 and EWQ-160, respectively. These results indicated extrusion affects the content of various amino acids differently and that the changes are dependent on the extrusion temperature. Similar result was also observed for fatty acids, organic acids, and phenolics. In conclusion, extrusion has potential in the processing of quinoas and the metabolic characterization of amino acids, fatty acids, organic acids, and phenolics in grains could be effectively analyzed using metabolomics.PMID:37254376 | DOI:10.1016/j.foodres.2023.112761

Key secondary metabolite markers for Wuchang Daohuaxiang rice discrimination in China

Wed, 31/05/2023 - 12:00
Food Res Int. 2023 Jul;169:112943. doi: 10.1016/j.foodres.2023.112943. Epub 2023 May 8.ABSTRACTThis study aimed to comprehensively elucidate the vital secondary metabolites of Wuchang Daohuaxiang (DHX) rice through widely targeted metabolomics analysis. Among the secondary metabolites detected, a total of 30 differential ones were screened out and categorized into 4 different classes, including 6 alkaloids (20%), 15 flavonoids (50%), 6 phenolic acids (20%), and 3 terpenoids (10%) between DHX and control groups. Of these, compounds as zarzissine, fagomine, arbutin, p-Hydroxypheny-β-D-allopyranoside, pimaric acid, kaurenoic acid, and isopimaric acid were more abundant in DHX than control group, with the possibility in serve as key secondary metabolites of DHX rice. Furthermore, arbutin, trigonelline and 6'-O-Feruloyl-D-sucrose were optimized as potential biomarkers for DHX rice discrimination. This study would supply data support for DHX rice authenticity and quality improvement.PMID:37254367 | DOI:10.1016/j.foodres.2023.112943

Cabernet sauvignon dry red wine ameliorates atherosclerosis in mice by regulating inflammation and endothelial function, activating AMPK phosphorylation, and modulating gut microbiota

Wed, 31/05/2023 - 12:00
Food Res Int. 2023 Jul;169:112942. doi: 10.1016/j.foodres.2023.112942. Epub 2023 May 4.ABSTRACTLimited evidence suggests that the abundance of antioxidant polyphenols in dry red wine (DRW) may prevent cardiovascular diseases, a benefit likely attributed to abundant antioxidant polyphenols present in DRW. Here, we examined the anti-atherosclerotic effect of Cabernet Sauvignon DRW (CSDRW) in a mouse model of atherosclerosis (AS) using metabolomic profiling and molecular techniques. Oral administration of CSDRW reduced atherosclerotic lesion size in ApoE-/- mice, alleviated hyperlipidemia, ameliorated hepatic lipid accumulation mediated by AMPK activation, and promoted lipid metabolism via PPARγ-LXR-α-ABCA1 pathway regulation. CSDRW increased the relative abundance of beneficial gut microbiota, including Bacteroidetes, Verrucomicrobiota, and Akkermansiaceae. Metabolic analysis using liquid chromatography-tandem mass spectrometry revealed that CSDRW contained various polyphenols, including flavanol, phenolic acid, flavonol, and resveratrol, which possibly mediate the beneficial effects in AS by reducing inflammation, restoring normal endothelial function, regulating hepatic lipid metabolism, and modulating gut microbiota composition.PMID:37254366 | DOI:10.1016/j.foodres.2023.112942

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