PubMed

Plant J. 2023 Jul 11. doi: 10.1111/tpj.16391. Online ahead of print.ABSTRACTDevelopmental transitions, occurring throughout the life cycle of plants, require precise regulation of metabolic processes to generate the energy and resources necessary for the committed growth processes. In parallel, the establishment of new cells, tissues and even organs, alongside their differentiation provoke profound changes in metabolism. It is increasingly being recognized that there is a certain degree of feedback regulation between the components and products of metabolic pathways and developmental regulators. The generation of large-scale metabolomics datasets during developmental transitions, in combination with molecular genetic approaches have helped to further our knowledge on the functional importance of metabolic regulation of development. In this perspective article, we provide insights into studies that elucidate interactions between metabolism and development at the temporal and spatial scales. We additionally discuss how this influences cell growth related processes. We also highlight how metabolic intermediates function as signaling molecules to direct plant development in response to changing internal and external conditions.PMID:37433681 | DOI:10.1111/tpj.16391

Anal Chem. 2023 Jul 11. doi: 10.1021/acs.analchem.3c00734. Online ahead of print.ABSTRACTMass spectrometry-based large-scale multi-omics research has proven to be powerful in answering biological questions; nonetheless, it faces many challenges from sample preparation to downstream data integration. To efficiently extract biomolecules of different physicochemical properties, preparation of various sample type needs specific tailoring, especially of difficult ones, such as Caenorhabditis elegans. In this study, we sought to develop a multi-omics sample preparation method starting with a single set ofC. elegans samples to save time, minimize variability, expand biomolecule coverage, and promote multi-omics integration. We investigated tissue disruption methods to effectively release biomolecules and optimized extraction strategies to achieve broader and more reproducible biomolecule coverage in proteomics, lipidomics, and metabolomics workflows. In our assessment, we also considered speediness and usability of the approaches. The developed method was validated through a study of 16C. elegans samples designed to shine light on mitochondrial unfolded protein response (UPRmt), induced by three unique stressors─knocking down electron transfer chain element cco-1, mitochondrial ribosome protein S5 mrps-5, and antibiotic treatment Doxycycline. Our findings suggested that the method achieved great coverage of proteome, lipidome, and metabolome with high reproducibility and validated that all stressors triggered UPRmt in C. elegans, although generating unique molecular signatures. Innate immune response was activated, and triglycerides were decreased under all three stressor conditions. Additionally, Doxycycline treatment elicited more distinct proteomic, lipidomic, and metabolomic response than the other two treatments. This method has been successfully used to process Saccharomyces cerevisiae (data not shown) and can likely be applied to other organisms for multi-omics research.PMID:37432911 | DOI:10.1021/acs.analchem.3c00734

J Proteome Res. 2023 Jul 11. doi: 10.1021/acs.jproteome.2c00788. Online ahead of print.ABSTRACTCommunity-acquired pneumonia (CAP) is a significant threat to human health and the leading cause of acute respiratory distress syndrome (ARDS). We aimed to reveal the metabolic profiling whether can be used for assessing CAP with or without ARDS (nARDS) and therapeutic effects on CAP patients after treatment. Urine samples were collected at the onset and recovery periods, and metabolomics was employed to identify robust biomarkers. 19 metabolites were significantly changed in the ARDS relative to nARDS, mainly involving purines and fatty acids. After treatment, 7 metabolites in the nARDS and 14 in the ARDS were found to be significantly dysregulated, including fatty acids and amino acids. In the validation cohort, we observed that the biomarker panel consisted of N2,N2-dimethylguanosine, 1-methyladenosine, 3-methylguanine, 1-methyladenosine, and uric acid exhibited better AUCs of 0.900 than pneumonia severity index and acute physiology and chronic health evaluation II (APACHE II) scores between the ARDS and nARDS. Combining L-phenylalanine, phytosphingosine, and N-acetylaspartylglutamate as biomarkers for discriminating the nARDS and ARDS patients after treatment exhibited good AUCs of 0.811 and 0.821, respectively. The metabolic pathway and defined biomarkers may serve as crucial indicators for predicting the development of ARDS in CAP patients and for assessing therapeutic effects.PMID:37432907 | DOI:10.1021/acs.jproteome.2c00788

J Nat Med. 2023 Jul 11. doi: 10.1007/s11418-023-01721-x. Online ahead of print.ABSTRACTPeony root is an important herbal drug used as an antispasmodic analgesic. To evaluate peony roots with different botanical origins, producing areas, and post-harvest processing, 1H NMR-based metabolomics analysis was employed. Five types of monoterpenoids, including albiflorin (4), paeoniflorin (6), and sulfonated paeoniflorin (25), and six other compounds, including 1,2,3,4,6-penta-O-galloyl-β-D-glucose (18), benzoic acid (21), gallic acid (22), and sucrose (26) were detected in the extracts of peony root samples. Among them, compounds 4, 6, 18, and total monoterpenoids including 21 were quantified by quantitative 1H NMR (qHNMR). Compound 25 was detected in 1H NMR spectra of sulfur-fumigated white peony root (WPR) extracts indicating that 1H NMR was a fast and effective method for identifying sulfur-fumigated WPR. The content of 26, the main factor affecting extract yield, increased significantly in peony root after low-temperature storage for one month, whereas that in WPR did not increase due to the boiling treatment after harvesting. We investigated the impact of preprocessing methods to such analysis for NMR data from commercial samples, resulting that the data matrix transformed from qHNMR spectra and normalized to internal standard were optimum for multivariate analysis. The multivariate analysis demonstrated that among commercial samples derived from P. lactiflora, peony root samples in Japanese market (PR) had high contents of 18 and 22, and red peony root (RPR) samples had high content of monoterpenoids represented by 6; and among RPR samples, those derived from P. veitchii showed higher contents of 18 and 22 than those from P. lactiflora. The 1H NMR-based metabolomics method coupled with qHNMR was useful for evaluation of peony root and would be applicable for other crude drugs.PMID:37432536 | DOI:10.1007/s11418-023-01721-x

Food Funct. 2023 Jul 11. doi: 10.1039/d3fo01551c. Online ahead of print.ABSTRACTProanthocyanidins (PAs) are one of the most commonly ingested polyphenols in the human diet, with a wide range of beneficial health effects. Remarkably, PAs have been reported to influence core and peripheral clock genes expression, and their effects may change in a time-of-day dependent manner. Therefore, the aim of this study was to investigate whether the capacity of PAs to modulate the metabolome is conditioned by the time-of-day in which these compounds are consumed in a diet- and sex-dependent manner. To do this, a grape seed proanthocyanidin extract (GSPE) was administered to female and male Fischer 344 rats at ZT0 (in the morning) and ZT12 (at night) and the GSPE administration time effect was evaluated on clock genes expression, melatonin hormone and serum metabolite levels in a healthy and obesogenic context. The results showed an administration time effect of GSPE on the metabolome in a sex and diet-dependent manner. Specifically, there was an effect on amino acid, lipid and cholate metabolite levels that correlated with the central clock genes expression. Therefore, this study shows a strong influence of sex and diet on the PAs effects on the metabolome, modulated in turn by the time-of-day.PMID:37432474 | DOI:10.1039/d3fo01551c

Nutrients. 2023 May 8;15(9):2219. doi: 10.3390/nu15092219.ABSTRACTWhile diet and nutrition are modifiable risk factors for many chronic and infectious diseases, their role in cancer prevention and control remains under investigation. The lack of clarity of some diet-cancer relationships reflects the ongoing debate about the relative contribution of genetic factors, environmental exposures, and replicative errors in stem cell division as determinate drivers of cancer risk. In addition, dietary guidance has often been based upon research assuming that the effects of diet and nutrition on carcinogenesis would be uniform across populations and for various tumor types arising in a specific organ, i.e., that one size fits all. Herein, we present a paradigm for investigating precision dietary patterns that leverages the approaches that led to successful small-molecule inhibitors in cancer treatment, namely understanding the pharmacokinetics and pharmacodynamics of small molecules for targeting carcinogenic mechanisms. We challenge the scientific community to refine the paradigm presented and to conduct proof-in-concept experiments that integrate existing knowledge (drug development, natural products, and the food metabolome) with developments in artificial intelligence to design and then test dietary patterns predicted to elicit drug-like effects on target tissues for cancer prevention and control. We refer to this precision approach as dietary oncopharmacognosy and envision it as the crosswalk between the currently defined fields of precision oncology and precision nutrition with the goal of reducing cancer deaths.PMID:37432381 | DOI:10.3390/nu15092219

Nutrients. 2023 May 4;15(9):2184. doi: 10.3390/nu15092184.ABSTRACTPediatric obesity is associated with alterations in the gut microbiota and its metabolites. However, how they influence obesity and the effect of lifestyle interventions remains unknown.. In this non-randomized clinical trial, we analyzed metabolomes and microbial features to understand the associated metabolic pathways and the effect of lifestyle interventions on pediatric obesity. Anthropometric/biochemical data and fasting serum, urine, and fecal samples were collected at baseline and after an eight-week, weight-reduction lifestyle modification program. Post-intervention, children with obesity were classified into responder and non-responder groups based on changes in total body fat. At baseline, serum L-isoleucine and uric acid levels were significantly higher in children with obesity compared with those in normal-weight children and were positively correlated with obesogenic genera. Taurodeoxycholic and tauromuricholic α + β acid levels decreased significantly with obesity and were negatively correlated with obesogenic genera. Branched-chain amino acid and purine metabolisms were distinguished metabolic pathways in the obese group. Post-intervention, urinary myristic acid levels decreased significantly in the responder group, showing a significant positive correlation with Bacteroides. Fatty acid biosynthesis decreased significantly in the responder group. Thus, lifestyle intervention with weight loss is associated with changes in fatty acid biosynthesis, and myristic acid is a possible therapeutic target for pediatric obesity.PMID:37432339 | DOI:10.3390/nu15092184

Nutrients. 2023 Apr 30;15(9):2161. doi: 10.3390/nu15092161.ABSTRACTRetinopathy is one of the leading causes of irreversible blindness and vision loss worldwide. Imbalanced nutrients play important roles in the pathogenesis and pathophysiology of retinal diseases. Branched-Chain Amino Acids (BCAAs), as essential amino acids, perform a variety of biological functions, including protein synthesis, glucose metabolism, lipid metabolism, inflammation, and oxidative stress in metabolic tissues of diabetes and aging-related diseases. Recently, it has been shown that BCAAs are highly related to neuroprotection, oxidative stress, inflammatory and glutamate toxicity in the retina of retinopathy. Therefore, this review summarizes the alterations of BCAA levels in retinopathy, especially diabetic retinopathy and aging-related macular disease, and the genetics, functions, and mechanisms of BCAAs in the retina as well as other metabolic tissues for reference. All of these efforts aim to provide fundamental knowledge of BCAAs for further discoveries and research on retina health based on the sensing and signaling of essential amino acids.PMID:37432261 | DOI:10.3390/nu15092161

Nutrients. 2023 Apr 26;15(9):2095. doi: 10.3390/nu15092095.ABSTRACTIntermittent fasting (IF) has been promoted as an alternative to dietary caloric restriction for the treatment of obesity. IF restricts the amount of food consumed and improves the metabolic balance by synchronizing it with the circadian rhythm. Dietary changes have a rapid effect on the gut microbiota, modulating the interaction between meal timing and host circadian rhythms. Our paper aims to review the relationships between IF and human gut microbiota. In this study, the primary area of focus was the effect of IF on the diversity and composition of gut microbiota and its relationship with weight loss and metabolomic alterations, which are particularly significant for metabolic syndrome characteristics. We discussed each of these findings according to the type of IF involved, i.e., time-restricted feeding, Ramadan fasting, alternate-day fasting, and the 5:2 diet. Favorable metabolic effects regarding the reciprocity between IF and gut microbiota changes have also been highlighted. In conclusion, IF may enhance metabolic health by modifying the gut microbiota. However additional research is required to draw definitive conclusions about this outcome because of the limited number and diverse designs of existing studies.PMID:37432222 | DOI:10.3390/nu15092095

Nutrients. 2023 Apr 25;15(9):2074. doi: 10.3390/nu15092074.ABSTRACTHypertension is closely related to metabolic dysregulation, which is associated with microbial dysbiosis and altered host-microbiota interactions. However, plasma metabolite profiles and their relationships to oral/gut microbiota in hypertension have not been evaluated in depth. Plasma, saliva, subgingival plaques, and feces were collected from 52 hypertensive participants and 24 healthy controls in a cross-sectional cohort. Untargeted metabolomic profiling of plasma was performed using high-performance liquid chromatography-mass spectrometry. Microbial profiling of oral and gut samples was determined via 16S rRNA and metagenomic sequencing. Correlations between metabolites and clinic parameters/microbiota were identified using Spearman's correlation analysis. Metabolomic evaluation showed distinct clusters of metabolites in plasma between hypertensive participants and control participants. Hypertensive participants had six significantly increased and thirty-seven significantly decreased plasma metabolites compared to controls. The plasma metabolic similarity significantly correlated with the community similarity of microbiota. Both oral and gut microbial community composition had significant correlations with metabolites such as Sphingosine 1-phosphate, a molecule involved in the regulation of blood pressure. Plasma metabolites had a larger number of significant correlations with bacterial genera than fungal genera. The shared oral/gut bacterial genera had more correlations with metabolites than unique genera but shared fungal genera and metabolites did not show clear clusters. The hypertension group had fewer correlations between plasma metabolites and bacteria/fungi than controls at species level. The integrative analysis of plasma metabolome and oral/gut microbiome identified unreported alterations of plasma metabolites in hypertension and revealed correlations between altered metabolites and oral/gut microbiota. These observations suggested metabolites and microbiota may become valuable targets for therapeutic and preventive interventions of hypertension.PMID:37432207 | DOI:10.3390/nu15092074

Nutrients. 2023 Apr 22;15(9):2026. doi: 10.3390/nu15092026.ABSTRACTBACKGROUND: Red beetroot is known to be a health-promoting food. However, little attention is placed on intestinal bioactive compound absorption. The aim of the study was to assess the urinary red beetroot juice (RBJ) intake biomarkers and possible differences in RBJ's micronutrient absorption at rest or after physical exercise.METHODS: This is a three-armed, single-blind study, involving seven healthy volunteers which were randomly divided into three groups and alternatively assigned to three experimental sessions: RBJ intake at rest, RBJ intake with physical activity, and placebo intake with physical activity. For each session, urine samples were collected before and 120, 180, and 240 min after the intake of RBJ or placebo. The same sampling times were employed for the experimental session at rest. The RBJ metabolic composition was also characterized to identify the urinary biomarkers derived from the intake.RESULTS: 4-methylpyridine-2-carboxylic acid, dopamine-3-O-sulfate, glutamine, and 3-hydroxyisobutyrate were identified as RBJ intake biomarkers. Physical activity significantly increased only the dopamine-3-O-sulfate excretion 120 min after RBJ intake.CONCLUSIONS: Urinary dopamine-3-O-sulfate is related to RBJ dopamine content, while 4-methylpyridine-2-carboxylic acid is a betanin or betalamic acid catabolite. The different excretions of these metabolites following physical activity suggest a possible effect on the RBJ uptake depending on different transport processes through the mucosa, namely diffusion-mediated transport for dopamine and saturable transcellular transport for betalamic acid derivatives. These results open new perspectives in improving the absorption of natural bioactive molecules through physical activity.PMID:37432172 | DOI:10.3390/nu15092026

Nutrients. 2023 Apr 22;15(9):2022. doi: 10.3390/nu15092022.ABSTRACTPlant extracts including secondary metabolites have anti-inflammatory and anti-obesity activities. This study was conducted to investigate the anti-obesity properties of fermented Artemisia annua (AW) and Salicornia herbacea (GW) in vitro and in mice. The metabolite profiling of AW and GW extracts was performed using UHPLC-LTQ-Orbitrap-MS/MS, and gene expression was analyzed using real-time PCR for adipocyte difference factors. The anti-obesity effects in mice were measured using serum AST, ALT, glucose, TG, and cholesterol levels. Metabolites of the plant extracts after fermentation showed distinct differences with increasing anti-obesity active substances. The efficacy of inhibitory differentiation adipogenesis of 3T3-L1 adipocytes was better for GW than AW in a concentration-dependent manner. RT-PCR showed that the GW extract significantly reduced the expression of genes involved in adipocyte differentiation and fat accumulation (C/EBPα, PPARγ, and Fas). In C57BL/6 mice fed the HFD, the group supplemented with AW and GW showed reduced liver weight, NAS value, and fatty liver by suppressing liver fat accumulation. The GW group significantly reduced ALT, blood glucose, TG, total cholesterol, and LDL-cholesterol. This study displayed significant metabolite changes through biotransformation in vitro and the increasing anti-obesity effects of GW and AW in mice. GW may be applicable as functional additives for the prevention and treatment of obesity.PMID:37432154 | DOI:10.3390/nu15092022

Microbiol Spectr. 2023 Jul 11:e0085223. doi: 10.1128/spectrum.00852-23. Online ahead of print.ABSTRACTPolymyxins are last-line antibiotics employed against multidrug-resistant (MDR) Klebsiella pneumoniae. Worryingly, polymyxin resistance is rapidly on the rise globally. Polymyxins initially target lipid A of lipopolysaccharides (LPSs) in the cell outer membrane (OM), causing disorganization and cell lysis. While most studies focus on how genetic variations confer polymyxin resistance, the mechanisms of membrane remodeling and metabolic changes in polymyxin-resistant strains remain unclear, thus hampering the development of effective therapies to treat severe K. pneumoniae infections. In the present study, lipid A profiling, OM lipidomics, genomics, and metabolomics were integrated to elucidate the global mechanisms of polymyxin resistance and metabolic adaptation in a polymyxin-resistant strain (strain S01R; MIC of >128 mg/L) obtained from K. pneumoniae strain S01, a polymyxin-susceptible (MIC of 2 mg/L), New Delhi metallo-β-lactamase (NDM)-producing MDR clinical isolate. Genomic analysis revealed a novel in-frame deletion at position V258 of PhoQ in S01R, potentially leading to lipid A modification with 4-amino-4-deoxy-l-arabinose (L-Ara4N) despite the absence of polymyxin B. Comparative metabolomic analysis revealed slightly elevated levels of energy production and amino acid metabolism in S01R compared to their levels in S01. Exposure to polymyxin B (4 mg/L for S01 and 512 mg/L for S01R) substantially altered energy, nucleotide, and amino acid metabolism and resulted in greater accumulation of lipids in both strains. Furthermore, the change induced by polymyxin B treatment was dramatic at both 1 and 4 h in S01 but only significant at 4 h in S01R. Overall, profound metabolic adaptation was observed in S01R following polymyxin B treatment. These findings contribute to our understanding of polymyxin resistance mechanisms in problematic NDM-producing K. pneumoniae strains and may facilitate the discovery of novel therapeutic targets. IMPORTANCE Antimicrobial resistance (AMR) is a major threat to global health. The emergence of resistance to the polymyxins that are the last line of defense in so-called Gram-negative "superbugs" has further increased the urgency to develop novel therapies. There are frequent outbreaks of K. pneumoniae infections in hospitals being reported, and polymyxin usage is increasing remarkably. Importantly, the polymyxin-resistant K. pneumoniae strains are imposing more severe consequences to health systems. Using metabolomics, lipid A profiling, and outer membrane lipidomics, our findings reveal (i) changes in the pentose phosphate pathway and amino acid and nucleotide metabolism in a susceptible strain following polymyxin treatment and (ii) how cellular metabolism, lipid A modification, and outer membrane remodeling were altered in K. pneumoniae following the acquisition of polymyxin resistance. Our study provides, for the first time, mechanistic insights into metabolic responses to polymyxin treatment in a multidrug-resistant, NDM-producing K. pneumoniae clinical isolate with acquired polymyxin resistance. Overall, these results will assist in identifying new therapeutic targets to combat and prevent polymyxin resistance.PMID:37432123 | DOI:10.1128/spectrum.00852-23

Gut Microbes. 2023 Jan-Dec;15(1):2231590. doi: 10.1080/19490976.2023.2231590.ABSTRACTThe gut microbiota affects hepatic drug metabolism. However, gut microbial factors modulating hepatic drug metabolism are largely unknown. In this study, using a mouse model of acetaminophen (APAP)-induced hepatotoxicity, we identified a gut bacterial metabolite that controls the hepatic expression of CYP2E1 that catalyzes the conversion of APAP to a reactive, toxic metabolite. By comparing C57BL/6 substrain mice from two different vendors, Jackson (6J) and Taconic (6N), which are genetically similar but harbor different gut microbiotas, we established that the differences in the gut microbiotas result in differential susceptibility to APAP-induced hepatotoxicity. 6J mice exhibited lower susceptibility to APAP-induced hepatotoxicity than 6N mice, and such phenotypic difference was recapitulated in germ-free mice by microbiota transplantation. Comparative untargeted metabolomic analysis of portal vein sera and liver tissues between conventional and conventionalized 6J and 6N mice led to the identification of phenylpropionic acid (PPA), the levels of which were higher in 6J mice. PPA supplementation alleviated APAP-induced hepatotoxicity in 6N mice by lowering hepatic CYP2E1 levels. Moreover, PPA supplementation also reduced carbon tetrachloride-induced liver injury mediated by CYP2E1. Our data showed that previously known PPA biosynthetic pathway is responsible for PPA production. Surprisingly, while PPA in 6N mouse cecum contents is almost undetectable, 6N cecal microbiota produces PPA as well as 6J cecal microbiota in vitro, suggesting that PPA production in the 6N gut microbiota is suppressed in vivo. However, previously known gut bacteria harboring the PPA biosynthetic pathway were not detected in either 6J or 6N microbiota, suggesting the presence of as-yet-unidentified PPA-producing gut microbes. Collectively, our study reveals a novel biological function of the gut bacterial metabolite PPA in the gut-liver axis and presents a critical basis for investigating PPA as a modulator of CYP2E1-mediated liver injury and metabolic diseases.PMID:37431867 | DOI:10.1080/19490976.2023.2231590

Gut Microbes. 2023 Jan-Dec;15(1):2232143. doi: 10.1080/19490976.2023.2232143.ABSTRACTThe gut microbiota and bile acid metabolism are key determinants of the response of inflammatory bowel disease to biologic therapy. However, the molecular mechanisms underlying the interactions between the response to anti-α4β7-integrin therapy and the gut microbiota and bile acid metabolism remain unknown. In this research, we investigated the role of gut microbiota-related bile acid metabolism on the response to anti-α4β7-integrin therapy in a humanized immune system mouse model with colitis induced by 2,4,6-trinitrobenzene sulfonic acid. We found that anti-α4β7-integrin significantly mitigated intestinal inflammation, pathological symptoms, and gut barrier disruption in remission-achieving colitis mice. Whole-genome shotgun metagenomic sequencing demonstrated that employing baseline microbiome profiles to predict remission and the treatment response was a promising strategy. Antibiotic-mediated gut microbiota depletion and fecal microbiome transplantation revealed that the baseline gut microbiota contained common microbes with anti-inflammatory effects and reduced mucosal barrier damage, improving the treatment response. Targeted metabolomics analysis illustrated that bile acids associated with microbial diversity were involved in colitis remission. Furthermore, the activation effects of the microbiome and bile acids on FXR and TGR5 were evaluated in colitis mice and Caco-2 cells. The findings revealed that the production of gastrointestinal bile acids, particularly CDCA and LCA, further directly promoted the stimulation of FXR and TGR5, significantly improving gut barrier function and suppressing the inflammatory process. Taken together, gut microbiota-related bile acid metabolism-FXR/TGR5 axis may be a potential mechanism for impacting the response to anti-α4β7-integrin in experimental colitis. Thus, our research provides novel insights into the treatment response in inflammatory bowel disease.PMID:37431863 | DOI:10.1080/19490976.2023.2232143

Environ Sci Technol. 2023 Jul 11. doi: 10.1021/acs.est.3c01746. Online ahead of print.ABSTRACTTriclosan (TCS), an antimicrobial compound, is known to have potential endocrine-disruptive properties, but the underlying toxic mechanisms at the metabolic level are not well understood. Here, we applied metabolomics and lipidomics combined with mass spectrometry imaging (MSI) to unveil the mechanisms of the enhanced growth of MCF-7 breast cancer cell spheroids (CCS) exposed to TCS. To obtain a wide coverage of metabolites and lipids by using MSI, we used techniques of matrix-assisted laser desorption/ionization (MALDI) and MALDI coupled with laser-postionization. The results showed that TCS and TCS sulfate penetrated into the entire area at 0-3 h and both localized in the inner area at 6 h. After 24 h, a portion of two compounds was released from CCS. Omic data indicated that TCS exposure induced alterations via several pathways, including energy metabolism and biosynthesis of glycerophospholipids and glycerolipids. Further MSI data revealed that the enhancement of energy supply in the peripheral area and the increase of energy storage in the inner area might contribute to the enhanced growth of MCF-7 breast CCS exposed to TCS. This study highlights the importance of integrating metabolite distributions and metabolic profiles to reveal the novel mechanisms of TCS-triggered endocrine disrupting effects.PMID:37431803 | DOI:10.1021/acs.est.3c01746

Alcohol (Hanover). 2023 Jul 11. doi: 10.1111/acer.15148. Online ahead of print.ABSTRACTBACKGROUND: Alcohol-associated liver disease (ALD) leads to millions of deaths worldwide annually. A few potential biomarkers have been discovered through metabolomics or proteomics. Tryptophan (Trp), one of the nine essential amino acids, has been extensively studied and has been shown to play significant roles in many mammalian physiological processes. However, Trp metabolism changes in ALD are not yet fully understood. Urine is an abundant and non-invasive source for disease biomarker discovery. The objective of the current study was to investigate whether the abundance of Trp metabolites in the urine of ALD patients is changed and if these changes in urine can serve as markers for differentiating between stages of ALD.METHOD: We quantified the concentration of Trp and its metabolites in the human urine samples of healthy controls (n = 18), patients with mild or moderate alcohol-related liver injury (n = 21), and patients with severe alcohol-associated hepatitis (AH) (n = 25) using both untargeted and targeted metabolomics.RESULTS: Eighteen Trp metabolites were identified and quantified from the untargeted metabolomics data. We then developed a targeted metabolomics method to quantify the Trp and its metabolites. Our developed method can simultaneously quantify 22 Trp metabolites within 15 mins, and 17 metabolites were quantified from the human urine samples. The data acquired in these two platforms agree and show that the Trp concentration is not affected by the severity of ALD. However, the abundance of 10 Trp metabolites is correlated with the model for end-stage liver disease (MELD) score, and the abundance of 9 metabolites have significant abundance changes between healthy control and patient groups.CONCLUSION: Our data demonstrate that Trp metabolism is altered by excessive alcohol consumption even though the concentration of Trp is not affected. Two Trp metabolites, quinolinic acid and indoxyl sulfate, correlate highly with ALD stage.PMID:37431708 | DOI:10.1111/acer.15148

Foods. 2022 Oct 20;11(20):3278. doi: 10.3390/foods11203278.ABSTRACTThe genus Hippophae (sea buckthorn) is widely cultivated and consumed in Asia and Europe. The fruit color is an important appearance and commercial trait for sea buckthorn, which is closely related to the biosynthesis and accumulation of various nutrients and pigments. The fruit colors of sea buckthorn are varied, which appear as yellow, orange, red, and brown. However, the nutrients and pigments forming different the fruit colors of sea buckthorn remain unclear. To investigate the mechanism of pigmentation of sea buckthorn fruit, integrative analyses of the transcriptome and targeted metabolome, including the carotenoids, flavonoids, and chlorophylls, were performed in five sea buckthorn varieties with different fruit colors. A total of 209 flavonoids and 41 carotenoids were identified in five sea buckthorn fruits of different colors. The types and contents of flavonoids and carotenoids in the five sea buckthorn fruits were significantly different. Interestingly, we only found a high content of chlorophyll (772.7 mg/kg) in the sea buckthorn fruit with a brown color. The quantities and relative proportions of the flavonoids, carotenoids, and chlorophyll led to the different colors of the sea buckthorn fruits. Using a weighted gene co-expression network analysis (WGCNA), the key genes related to the carotenoids and chlorophyll metabolism were identified. The high content of chlorophylls in the brown fruit was closely related to the downregulated expression of key genes in the chlorophyll degradation pathway, including SGR, SGRL, PPH, NYC1, and HCAR. Our results provide new insights into the roles of flavonoids, carotenoids, and chlorophylls in the formation of fruit color in sea buckthorn.PMID:37431026 | DOI:10.3390/foods11203278

Foods. 2022 Oct 20;11(20):3269. doi: 10.3390/foods11203269.ABSTRACTThe supercritical CO2-based decaffeination (SCD) method can be used to prepare decaffeinated tea, but its overall effect on the phytochemicals, volatiles, and sensory qualities of green and black teas is still unclear, and its suitability to prepare decaffeinated green and black teas still needs to be compared. This study revealed the effect of SCD on phytochemicals, volatiles, and sensory qualities in black and green tea prepared from the same tea leaves, and compared the suitability of preparing decaffeinated green and black teas using SCD. The results showed that the SCD could remove 98.2 and 97.1% of the caffeine in green and black tea, respectively. However, it can cause further losses of phytochemicals in green and black teas, specifically the loss of epigallocatechin gallate, epigallocatechin, epicatechin gallate, and gallocatechin gallate in green tea and the loss of theanine and arginine in green and black teas. After the decaffeination, both green and black teas lost some volatiles but also generated new volatiles. Especially, the fruit/flower-like aroma, ocimene, linalyl acetate, geranyl acetate, and D-limonene, were generated in the decaffeinated black tea, while herbal/green-like aroma, β-cyclocitral, 2-ethylhexanol, and safranal, were generated in the decaffeinated green tea. The overall acceptance of decaffeinated green tea decreased due to the substantial reduction in bitterness and astringency, while the overall acceptance of decaffeinated black tea significantly increased. Therefore, SCD is more suitable for the preparation of decaffeinated black tea.PMID:37431017 | DOI:10.3390/foods11203269

Foods. 2022 Oct 18;11(20):3248. doi: 10.3390/foods11203248.ABSTRACTFlavor is one of the most important characteristics that directly determines the popularity of a food. Moreover, the flavor of fruits is determined by the interaction of multiple metabolic components. Pepino, an emerging horticultural crop, is popular for its unique melon-like flavor. We analyzed metabolomics data from three different pepino growing regions in Haidong, Wuwei, and Jiuquan and counted the status of sweetness, acidity, flavor, and overall liking ratings of pepino fruit in these three regions by sensory panels. The metabolomics and flavor ratings were also integrated and analyzed using statistical and machine learning models, which in turn predicted the sensory panel ratings of consumers based on the chemical composition of the fruit. The results showed that pepino fruit produced in the Jiuquan region received the highest ratings in sweetness, flavor intensity, and liking, and the results with the highest contribution based on sensory evaluation showed that nucleotides and derivatives, phenolic acids, amino acids and derivatives, saccharides, and alcohols were rated in sweetness (74.40%), acidity (51.57%), flavor (56.41%), and likability (33.73%) dominated. We employed 14 machine learning strategies trained on the discovery samples to accurately predict the outcome of sweetness, sourness, flavor, and liking in the replication samples. The Radial Sigma SVM model predicted with better accuracy than the other machine learning models. Then we used the machine learning models to determine which metabolites influenced both pepino flavor and consumer preference. A total of 27 metabolites most important for pepino flavor attributes to distinguish pepino originating from three regions were screened. Substances such as N-acetylhistamine, arginine, and caffeic acid can enhance pepino's flavor intensity, and metabolites such as glycerol 3-phosphate, aconitic acid, and sucrose all acted as important variables in explaining the liking preference. While glycolic acid and orthophosphate inhibit sweetness and enhance sourness, sucrose has the opposite effect. Machine learning can identify the types of metabolites that influence fruit flavor by linking metabolomics of fruit with sensory evaluation among consumers, which conduces breeders to incorporate fruit flavor as a trait earlier in the breeding process, making it possible to select and release fruit with more flavor.PMID:37430996 | DOI:10.3390/foods11203248