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

Dynamic fecal microenvironment properties enable predictions and understanding of peripartum blood oxidative status and non-esterified fatty acids in dairy cows

Sun, 10/09/2023 - 12:00
J Dairy Sci. 2023 Sep 8:S0022-0302(23)00619-7. doi: 10.3168/jds.2022-23066. Online ahead of print.ABSTRACTThe transition period in dairy cows is a critical stage and peripartum oxidative status, negative energy balance (NEB) and inflammation are highly prevalent. Fecal microbial metabolism is closely associated with blood oxidative status and nonesterified fatty acids (NEFA) levels. Here, we investigated dynamic changes in total oxidative status markers and NEFA in blood, fecal microbiome and metabolome of 30 dairy cows during transition (-21d, -7d, +7d, +21d relative to calving). Then the Bayesian network and 9 machine learning algorithms were applied to dismantle their relationship. Our results show that the oxidative status indicator (OSI) of -21d, -7d, +7d was higher than +21d (P < 0.001). The plasma concentration of nonesterified fatty acids (NEFA) peaked on +7d (P < 0.001). For fecal microenvironment, a decline in bacterial α diversity was observed at postpartum (P < 0.001) and in bacterial interactions at +7d (P = 0.014). Conversely, microbial metabolites involved in carbohydrate, lipid and energy metabolism increased on +7d (P < 0.05). A correlation analysis revealed that 11 and 10 microbial metabolites contributed to OSI and NEFA variations, respectively (Arc. strength >0.5). The support vector machine (SVM) radial model showed the highest average predictive accuracy (100% and 88.9% in the test and external data sets) for OSI using 1 metabolite and 3 microbiota. SVM radial model also showed the highest average diagnostic accuracy (100% and 91% in the test and external data sets) for NEFA with 2 metabolites and 3 microbiota. Our results reveal a relationship between variation in the fecal microenvironment and indicators of oxidative status, NEB and inflammation, which provide a theoretical basis for the prevention and precise regulation of peripartum oxidative status and NEB.PMID:37690725 | DOI:10.3168/jds.2022-23066

Metabolic signature biomarkers for predicting the recurrence of urological cancers

Sun, 10/09/2023 - 12:00
Clin Chim Acta. 2023 Sep 8:117553. doi: 10.1016/j.cca.2023.117553. Online ahead of print.ABSTRACTA significant number of patients diagnosed with localized urological cancers experience relapse and disease progression after surgery. Hence, molecular markers for patient risk stratification are needed to improve the current management guidelines. This article critically reviews for the first time, to our knowledge, the promise of metabolomics-based approaches to identify metabolic signatures as candidate prognostic biomarkers to predict recurrences at the time of surgery in prostate cancer (PCa), bladder cancer (BCa), and renal cell carcinoma (RCC). Dysregulations in the levels of several tumoral, circulating, and excreted metabolites have been reported in PCa patients experiencing recurrence within 1.5 to 8 years of follow-up. The combination of these metabolic biomarkers with clinical parameters (e.g., pathological T stage, Gleason score) has shown great potential to improve the predictive ability of PCa recurrence. In contrast, predictive biomarkers of recurrence in BCa and RCC have been poorly explored. Overall, this review highlights the great potential of metabolomics in discovering prognostic biomarkers for a more accurate patient risk stratification in urological cancers.PMID:37690663 | DOI:10.1016/j.cca.2023.117553

Akkermansia muciniphila: A potential target and pending issues for oncotherapy

Sun, 10/09/2023 - 12:00
Pharmacol Res. 2023 Sep 8:106916. doi: 10.1016/j.phrs.2023.106916. Online ahead of print.ABSTRACTIn the wake of the development of metagenomic, metabolomic, and metatranscriptomic approaches, the intricate interactions between the host and various microbes are now being progressively understood. Numerous studies have demonstrated evident changes in gut microbiota during the process of a variety of diseases, such as diabetes, obesity, aging, and cancers. Notably, gut microbiota is viewed as a potential source of novel therapeutics. Currently, Next-generation probiotics (NGPs) are gaining popularity as therapeutic agents that alter the gut microbiota and affect cancer development. Akkermansia muciniphila (A. muciniphila), a representative commensal bacterium, has received substantial attention over the past decade as a promising NGP. The components and metabolites of A. muciniphila can directly or indirectly affect tumorigenesis, in particular through its effects on antitumor immunosurveillance, including the stimulation of pattern recognition receptors (PRRs), which also leads to better outcomes in a variety of situations, including the prevention and curation of cancers. In this article, we systematically summarize the role of A. muciniphila in tumorigenesis (involving gastrointestinal and non-gastrointestinal cancers) and in tumor therapy. In particular, we carefully discuss some critical scientific issues that need to be solved for the future using A. muciniphila as a representative beneficial bacterium in tumor treatment, which might provide bright clues and assistance for the application of drugs targeting A. muciniphila in clinical oncotherapy.PMID:37690533 | DOI:10.1016/j.phrs.2023.106916

Adaptation of the AbsoluteIDQ p180 kit to the analysis of metabolites in the human aqueous humor

Sun, 10/09/2023 - 12:00
J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Sep 8;1229:123880. doi: 10.1016/j.jchromb.2023.123880. Online ahead of print.ABSTRACTThe aim of this study was to use the commercial kit AbsoluteIDQ p180 (Biocrates) for the quantification of metabolites in aqueous humor (AH), as well as to determine the optimal volume of AH that is necessary to obtain reliable and reproducible results. Different volumes of AH (10 µl, 20 µl, and 30 µl) were tested. Of the 188 metabolites measurable with the Biocrates kit, 69 were detected in AH. Depending on the volume used, 41, 51, and 63 metabolites were measured using 10 µl, 20 µl, and 30 µl of AH, respectively. The repeatability of the measurements improved with increasing AH volume. Considering only those metabolites that were obtained with a CV < 15%, 34 metabolites at 10 µl, 41 at 20 µl, and 44 at 30 µl AH were received. On this basis, it can be concluded that the tested method can be successfully applied to analyze metabolites in the human AH. To achieve the most comprehensive detection range and highest repeatability of measurements, it is recommended to use 30 µl AH.PMID:37690387 | DOI:10.1016/j.jchromb.2023.123880

Astragaloside IV protects against lung injury and pulmonary fibrosis in COPD by targeting GTP-GDP domain of RAS and downregulating the RAS/RAF/FoxO signaling pathway

Sun, 10/09/2023 - 12:00
Phytomedicine. 2023 Sep 8;120:155066. doi: 10.1016/j.phymed.2023.155066. Online ahead of print.ABSTRACTBACKGROUND: Pulmonary fibrosis is a chronic progressive interstitial lung disease characterized by the replacement of lung parenchyma with fibrous scar tissue, usually as the final stage of lung injury like COPD. Astragaloside IV (AST), a bioactive compound found in the Astragalus membranaceus (Fisch.) used in traditional Chinese medicine, has been shown to improve pulmonary function and exhibit anti-pulmonary fibrosis effects. However, the exact molecular mechanisms through which it combats pulmonary fibrosis, especially in COPD, remain unclear.PURPOSE: This study aimed to identify the potential therapeutic target and molecular mechanisms for AST in improving lung injury especially treating COPD type pulmonary fibrosis both in vivo and in vitro.METHODS: Multi lung injury models were established in mice using lipopolysaccharide (LPS), cigarette smoke (CS), or LPS plus CS to simulate the processes of pulmonary fibrosis in COPD. The effect of AST on lung function protection was evaluated, and proteomic and metabolomic analysis were applied to identify the signaling pathway affected by AST and to find potential targets of AST. The interaction between AST and wild-type and mutant RAS proteins was studied. The RAS/RAF/FoxO signaling pathway was stimulated in BEAS-2B cells and in mice lung tissues by LPS plus CS to investigate the anti-pulmonary fibrosis mechanism of AST analyzed by western blotting. The regulatory effects of AST on the RAS/RAF/FoxO pathway dependent on RAS were further confirmed using RAS siRNA.RESULTS: RAS was predicted and identified as the target protein of AST in anti-pulmonary fibrosis in COPD and improving lung function. The administration of AST was observed to impede the conversion of fibroblasts into myofibroblasts, reduce the manifestation of inflammatory factors and extracellular matrix, and hinder the activation of epithelial mesenchymal transition (EMT). Furthermore, AST significantly suppressed the RAS/RAF/FoxO signaling pathway in both in vitro and in vivo settings.CONCLUSION: AST exhibited lung function protection and anti-pulmonary fibrosis effect by inhibiting the GTP-GDP domain of RAS, which downregulated the RAS/RAF/FoxO signaling pathway. This study revealed AST as a natural candidate molecule for the protection of pulmonary fibrosis in COPD.PMID:37690229 | DOI:10.1016/j.phymed.2023.155066

Microbial modifications with Lycium barbarum L. oligosaccharides decrease hepatic fibrosis and mitochondrial abnormalities in mice

Sun, 10/09/2023 - 12:00
Phytomedicine. 2023 Sep 4;120:155068. doi: 10.1016/j.phymed.2023.155068. Online ahead of print.ABSTRACTBACKGROUND: Lycium barbarum L. is a typical Chinese herbal and edible plant and are now consumed globally. Low molecular weight L. barbarum L. oligosaccharides (LBO) exhibit better antioxidant activity and gastrointestinal digestibility in vitro than high molecular weight polysaccharides. However, the LBO on the treatment of liver disease is not studied.PURPOSE: Modification of the gut microbial ecosystem by LBO is a promising treatment for liver fibrosis.STUDY DESIGN AND METHODS: Herein, LBO were prepared and characterized. CCl4-treated mice were orally gavaged with LBO and the effects on hepatic fibrosis and mitochondrial abnormalities were evaluated according to relevant indicators (gut microbiota, faecal metabolites, and physiological and biochemical indices).RESULTS: The results revealed that LBO, a potential prebiotic source, is a pyranose cyclic oligosaccharide possessing α-glycosidic and β-glycosidic bonds. Moreover, LBO supplementation restored the configuration of the bacterial community, enhanced the proliferation of beneficial species in the gastrointestinal tract (e.g., Bacillus, Tyzzerella, Fournierella and Coriobacteriaceae UCG-002), improved microbial metabolic alterations (i.e., carbohydrate metabolism, vitamin metabolism and entero-hepatic circulation), and increased antioxidants, including doxepin, in mice. Finally, LBO administration reduced serum inflammatory cytokine and hepatic hydroxyproline levels, improved intestinal and hepatic mitochondrial functions, and ameliorated mouse liver fibrosis.CONCLUSION: These findings indicate that LBO can be utilized as a prebiotic and has a remarkable ability to mitigate liver fibrosis.PMID:37690228 | DOI:10.1016/j.phymed.2023.155068

Association of maternal metals exposure, metabolites and birth outcomes in newborns: A prospective cohort study

Sun, 10/09/2023 - 12:00
Environ Int. 2023 Sep 3;179:108183. doi: 10.1016/j.envint.2023.108183. Online ahead of print.ABSTRACTBACKGROUND: Maternal exposure to metals may pose a risk to the health of newborns, however, the underlying mechanisms remain ambiguous. Herein, we aimed to investigate the influence of metals exposure on birth outcomes and reveal the importance of metabolites in the exposure-outcomes association by using metabolomics methods.METHODS: In our study, 292 mother-pairs were included who were recruited from the affiliated hospitals of Nanjing Medical University between 2006 and 2011. We measured fifteen metals (mercury, lead, vanadium, arsenic, zinc, cadmium, rubidium, copper, cobalt, iron, molybdenum, strontium, thallium, magnesium and calcium) and metabolites in maternal second trimester serums by using inductively coupled plasma mass spectrometry and ultra-high performance liquid chromatography high resolution accurate mass spectrometry, respectively. A multi-step statistical analysis strategy including exposome-wide association study (ExWAS) model, variable selection models and multiple-exposure models were performed to systematically appraise the associations of individual and mixed metals exposure with birth outcomes. Furthermore, differential metabolites that associated with metals exposure and birth outcomes were identified using linear regression models.RESULTS: Metal's levels in maternal serums ranged from 0.05 μg/L to 1864.76 μg/L. In the ExWAS model, maternal exposure to arsenic was negatively associated with birth weight (β = 188.83; 95% CI: -368.27, -9.39), while maternal mercury exposure showed a positive association (β = 533.65; 95%CI: 179.40, 887.90) with birth weight. Moreover, each unit increase in mercury (1 ng/mL-log transformed) was associated with a 1.82 week-increase (95%CI: 0.85, 2.79) in gestational age. These findings were subsequently validated by variable selection models and multiple exposure models. Metabolomic analysis further revealed the significant role of 3-methyladenine in the relationship between arsenic exposure and birth weight.CONCLUSION: This study provides new epidemiological evidence indicating the associations of metals exposure and neonatal birth outcomes, and emphasizes the potential role of metabolite biomarkers and their importance in monitoring adverse birth outcomes.PMID:37690219 | DOI:10.1016/j.envint.2023.108183

The identification of key metabolites and mechanisms during isoniazid/rifampicin-induced neurotoxicity and hepatotoxicity in a mouse model by HPLC-TOF/MS-based untargeted urine metabolomics

Sun, 10/09/2023 - 12:00
J Pharm Biomed Anal. 2023 Sep 6;236:115709. doi: 10.1016/j.jpba.2023.115709. Online ahead of print.ABSTRACTThe co-administration of isoniazid (INH) and rifampicin (RIF) is associated with hepatotoxicity and neurotoxicity. To systematically investigate the mechanisms of hepatotoxicity and neurotoxicity induced by INH/RIF, we used high performance liquid chromatography-time of flight mass spectrometry (HPLC-TOF/MS)-based untargeted metabolomics to analyze urine from a mouse model and screened a range of urinary biomarkers. Mice were orally co-administered with INH (120 mg/kg) and RIF (240 mg/kg) and urine samples were collected on days 0, 7, 14 and 21. Hepatotoxicity and neurotoxicity were assessed by samples of liver, brain and kidney tissue which were harvested for histological analysis. Toxicity analysis revealed that INH/RIF caused hepatotoxicity and neurotoxicity in a time-dependent manner; compared with day 0, the levels of 35, 82 and 86 urinary metabolites were significantly different on days 7, 14 and 21, respectively. Analysis showed that by day 21, exposure to INH+RIF had caused disruption in vitamin B6 metabolism; the biosynthesis of unsaturated fatty acids; tyrosine, taurine, hypotaurine metabolism; the synthesis of ubiquinone and other terpenoid-quinones; and the metabolism of tryptophan, nicotinate and nicotinamide. Nicotinic acid, nicotinuric acid and kynurenic acid were identified as sensitive urinary biomarkers that may be useful for the diagnosis and evaluation of toxicity.PMID:37690188 | DOI:10.1016/j.jpba.2023.115709

Unique and generic crossed metabolism in response to four sub-lethal environmental stresses in the oriental fruit fly, Bactrocera dorsalis Hendel

Sun, 10/09/2023 - 12:00
Ecotoxicol Environ Saf. 2023 Sep 8;264:115434. doi: 10.1016/j.ecoenv.2023.115434. Online ahead of print.ABSTRACTBactrocera dorsalis is a well-known invasive pest that causes considerable ecological and economic losses worldwild. Although it has a wide environmental tolerance, few studies have reported its mechanism of adaptation to multiple sub-lethal environmental stresses. In this study, 38, 41, 39 and 34 metabolites changed significantly in B. dorsalis under four sub-lethal stresses (heat, cold, desiccation and hypoxia), as found by the metabolomic method. Therein, lactic acid and pyruvic acid were induced, whereas metabolites in the tricarboxylic acid (TCA) cycle such as citric acid, α-ketoglutarate acid, malic acid and fumaric acid were reduced under at least one of the stresses. Enzyme activity and quantitative polymerase chain reaction (qPCR) analyses verified the repression of pyruvic acid proceeding into the TCA cycle. In addition, the levels of several cryoprotectants and membrane fatty acids in B. dorsalis were altered. The findings indicated that B. dorsalis has evolved shared metabolic pathways to adapt to heat, hypoxia and desiccation stresses, such as reducing energy consumption by activating the anaerobic glycolytic metabolism. Cryoprotectants and membrane fatty acids were produced to improve the efficiency of stress resistance. This study revealed the unique and generic crossed physiological mechanism of insects to adapt to various environmental stresses.PMID:37690174 | DOI:10.1016/j.ecoenv.2023.115434

Multi-omic analyses and network biology in cardiovascular disease

Sun, 10/09/2023 - 12:00
Proteomics. 2023 Sep 10:e2200289. doi: 10.1002/pmic.202200289. Online ahead of print.ABSTRACTHeart disease remains a leading cause of death in North America and worldwide. Despite advances in therapies, the chronic nature of cardiovascular diseases ultimately results in frequent hospitalizations and steady rates of mortality. Systems biology approaches have provided a new frontier toward unraveling the underlying mechanisms of cell, tissue, and organ dysfunction in disease. Mapping the complex networks of molecular functions across the genome, transcriptome, proteome, and metabolome has enormous potential to advance our understanding of cardiovascular disease, discover new disease biomarkers, and develop novel therapies. Computational workflows to interpret these data-intensive analyses as well as integration between different levels of interrogation remain important challenges in the advancement and application of systems biology-based analyses in cardiovascular research. This review will focus on summarizing the recent developments in network biology-level profiling in the heart, with particular emphasis on modeling of human heart failure. We will provide new perspectives on integration between different levels of large "omics" datasets, including integration of gene regulatory networks, protein-protein interactions, signaling networks, and metabolic networks in the heart.PMID:37691071 | DOI:10.1002/pmic.202200289

The Role of Tryptophan Metabolism in the Occurrence and Progression of Acute and Chronic Kidney Diseases

Sun, 10/09/2023 - 12:00
Mol Nutr Food Res. 2023 Sep 10:e2300218. doi: 10.1002/mnfr.202300218. Online ahead of print.ABSTRACTAcute kidney injury (AKI) and chronic kidney disease (CKD) are common kidney diseases in clinics with high morbidity and mortality, but their pathogenesis is intricate. Tryptophan (Trp) is a fundamental amino acid for humans, and its metabolism produces various bioactive substances involved in the pathophysiology of AKI and CKD. Metabolomic studies manifest that Trp metabolites like kynurenine (KYN), 5-hydroxyindoleacetic acid (5-HIAA), and indoxyl sulfate (IS) increase in AKI or CKD and act as biomarkers that facilitate the early identification of diseases. Meanwhile, KYN and IS act as ligands to exacerbate kidney damage by activating aryl hydrocarbon receptor (AhR) signal transduction. The reduction of renal function can cause the accumulation of Trp metabolites which in turn accelerate the progression of AKI or CKD. Besides, gut dysbiosis induces the expansion of Enterobacteriaceae family to produce excessive IS, which cannot be excreted due to the deterioration of renal function. The application of Trp metabolism as a target in AKI and CKD will also be elaborated. Thus, this study aims to elucidate Trp metabolism in the development of AKI and CKD, and explores the relative treatment strategies by targeting Trp from the perspective of metabolomics to provide a reference for their diagnosis and prevention.PMID:37691068 | DOI:10.1002/mnfr.202300218

Abscisic acid promotes plant acclimation to the combination of salinity and high light stress

Sun, 10/09/2023 - 12:00
Plant Physiol Biochem. 2023 Sep 6;203:108008. doi: 10.1016/j.plaphy.2023.108008. Online ahead of print.ABSTRACTPlants encounter combinations of different abiotic stresses such as salinity (S) and high light (HL). These environmental conditions have a detrimental effect on plant growth and development, posing a threat to agricultural production. Metabolic changes play a crucial role in enabling plants to adapt to fluctuations in their environment. Furthermore, hormones such as abscisic acid (ABA), jasmonic acid (JA) and salicylic acid (SA) have been previously identified as regulators of plant responses to different abiotic stresses. Here we studied the response of Arabidopsis wild type (Col and Ler) plants and mutants impaired in hormone biosynthesis (aba2-11 and aba1-1 in ABA, aos in JA and sid2 in SA) to the combination of S and HL (S + HL). Our findings showed that aba2-11 plants displayed reduced growth, impaired photosystem II (PSII) function, increased leaf damage, and decreased survival compared to Col when subjected to stress combination. However, aos and sid2 mutants did not display significant changes in response to S + HL compared to Col, indicating a key role for ABA in promoting plant tolerance to S + HL and suggesting a marginal role for JA and SA in this process. In addition, we revealed differences in the metabolic response of plants to S + HL compared to S or HL. The analysis of altered metabolic pathways under S + HL suggested that the accumulation of flavonoids is ABA-dependent, whereas the accumulation of branched-chain amino acids (BCAAs) and proline is ABA-independent. Therefore, our study uncovered a key function for ABA in regulating the accumulation of different flavonoids in plants during S + HL.PMID:37690143 | DOI:10.1016/j.plaphy.2023.108008

Comparative analysis of key precursors and metabolites involved in flavor formation of different rapid-fermented Chinese fish sauces based on untargeted metabolomics analysis

Sun, 10/09/2023 - 12:00
Food Chem. 2023 Jul 28;433:136998. doi: 10.1016/j.foodchem.2023.136998. Online ahead of print.ABSTRACTOur study aimed to characterize the flavor precursors and metabolite profiles during fermentation of three rapid-fermented fish sauces (koji fermentation (YQ), insulation fermentation with koji (BWQ) and insulation fermentation with enzyme (BWE)) by a comparative metabolomics analysis. The total amount of free amino acids and free fatty acids in BWQ and BWE samples was significantly higher than that in YQ sample during fermentation, and C16:0, C22:6, C18:1, C14:1, C18:0 and C20:5 were deemed as key flavor precursors of three fish sauces. We identified 51, 47 and 45 differential metabolites as crucial components in YQ, BWE and BWQ samples. Specific metabolites in three samples were mainly related to amino acid metabolism, especially histidine, cysteine and methionine metabolism. Furthermore, 5 bacteria genera exhibited positive impacts on the generation of various flavor-related metabolites. This study provides a theoretical basis for targeted control of flavor and quality in the production of rapid-fermented fish sauce.PMID:37690140 | DOI:10.1016/j.foodchem.2023.136998

Multi-tissue transcriptomic and serum metabolomic assessment reveals systemic implications of acute ozone-induced stress response in male Wistar Kyoto rats

Sun, 10/09/2023 - 12:00
Metabolomics. 2023 Sep 10;19(9):81. doi: 10.1007/s11306-023-02043-5.ABSTRACTAir pollutant exposures have been linked to systemic disease; however, the underlying mechanisms between responses of the target tissue and systemic effects are poorly understood. A prototypic inducer of stress, ozone causes respiratory and systemic multiorgan effects through activation of a neuroendocrine stress response. The goal of this study was to assess transcriptomic signatures of multiple tissues and serum metabolomics to understand how neuroendocrine and adrenal-derived stress hormones contribute to multiorgan health outcomes. Male Wistar Kyoto rats (12-13 weeks old) were exposed to filtered air or 0.8 ppm ozone for 4-hours, and blood/tissues were collected immediately post-exposure. Each tissue had distinct expression profiles at baseline. Ozone changed 1,640 genes in lung, 274 in hypothalamus, 2,516 in adrenals, 1,333 in liver, 1,242 in adipose, and 5,102 in muscle (adjusted p-value < 0.1, absolute fold-change > 50%). Serum metabolomic analysis identified 863 metabolites, of which 447 were significantly altered in ozone-exposed rats (adjusted p-value < 0.1, absolute fold change > 20%). A total of 6 genes were differentially expressed in all 6 tissues. Glucocorticoid signaling, hypoxia, and GPCR signaling were commonly changed, but ozone induced tissue-specific changes in oxidative stress, immune processes, and metabolic pathways. Genes upregulated by TNF-mediated NFkB signaling were differentially expressed in all ozone-exposed tissues, but those defining inflammatory response were tissue-specific. Upstream predictor analysis identified common mediators of effects including glucocorticoids, although the specific genes responsible for these predictors varied by tissue. Metabolomic analysis showed major changes in lipids, amino acids, and metabolites linked to the gut microbiome, concordant with transcriptional changes identified through pathway analysis within liver, muscle, and adipose tissues. The distribution of receptors and transcriptional mechanisms underlying the ozone-induced stress response are tissue-specific and involve induction of unique gene networks and metabolic phenotypes, but the shared initiating triggers converge into shared pathway-level responses. This multi-tissue transcriptomic analysis, combined with circulating metabolomic assessment, allows characterization of the systemic inhaled pollutant-induced stress response.PMID:37690105 | DOI:10.1007/s11306-023-02043-5

Characterization of chemoresistant human non-small cell lung cancer cells by metabolic and lipidomic profiling

Sun, 10/09/2023 - 12:00
Metabolomics. 2023 Sep 10;19(9):80. doi: 10.1007/s11306-023-02045-3.ABSTRACTINTRODUCTION: Lung cancer is one of the most malignant cancers and the leading cause of cancer-related deaths worldwide, while acquired chemoresistance would represent a major problem in the treatment of non-small cell lung cancer (NSCLC) because of the reduced treatment effect and increased rates of recurrence.METHODS: To establish the chemoresistant NSCLC cells, doxorubicin was treated to A549 cells over 3 months at gradually increasing concentrations from 0.03 to 0.5 µM. Real-time PCR and Western blotting were employed for investigating mRNA and protein expression of the glutathione peroxidase (GPX) protein family and multidrug resistance protein 1 (MRP1) in A549 and A549/CR cells. We also employed gas chromatography mass-spectrometry and nano electrospray ionization mass-spectrometry coupled with multivariate statistical analysis to characterize the unique metabolic and lipidomic profiles of chemoresistant NSCLC cells in order to identify potential therapeutic targets.RESULTS: Reactive oxygen species levels were decreased, and mRNA and protein levels of GPX2 and multidrug resistance protein 1 (MRP1) were increased in A549/CR. We identified 87 metabolites and intact lipid species in A549 and A549/CR. Among these metabolites, lactic acid, glutamic acid, glycine, proline, aspartic acid, succinic acid, and ceramide, alongside the PC to PE ratio, and arachidonic acid-containing phospholipids were suggested as characteristic features of chemoresistant NSCLC cells (A549/CR).CONCLUSIONS: This study reveals characteristic feature differences between drug-resistance NSCLC cells and their parental cells. We suggest potential therapeutic targets in chemoresistant NSCLC. Our results provide new insight into metabolic and lipidomic alterations in chemoresistant NSCLC. This could be used as fundamental information to develop therapeutic strategies for the treatment of chemoresistant NSCLC patients.PMID:37690093 | DOI:10.1007/s11306-023-02045-3

Chemical markers of a rare honey from the traditional spice plant Amomum tsao-ko Crevost et Lemarié, via integrated GC-MS and LC-MS approaches

Sun, 10/09/2023 - 12:00
Food Res Int. 2023 Oct;172:113234. doi: 10.1016/j.foodres.2023.113234. Epub 2023 Jul 5.ABSTRACTThe precious medicinal plant, Amomum tsao-ko Crevost et Lemarié, is the nectariferous plant from which the rare Amomum tsao-ko Crevost et Lemarié honey (ATH) is produced. Presently, chemical markers for authentication of this honey are not available due to the lack of data on its chemical composition. Here, we analyzed the volatile components and their odor activity values (OAVs), which revealed that the unique aroma was mildly flowery and fruity, accompanied by subtle sweet and fresh undertones. Since non-volatile chemicals are more reliable markers for routine authentication, we used a metabolomic approach combined with NMR-based identification to find and confirm a suitable compound to unambiguously distinguish ATH from other honeys. Isorhamnetin 3-O-neohesperidoside ranged from 3.62 to 9.38 mg/kg in ATH and was absent in the other tested honeys. In sum, the study uncovered unique chemical characteristics of ATH that will be helpful to control its quality.PMID:37689964 | DOI:10.1016/j.foodres.2023.113234

Identification of nonvolatile chemical constituents in Chinese Huangjiu using widely targeted metabolomics

Sun, 10/09/2023 - 12:00
Food Res Int. 2023 Oct;172:113226. doi: 10.1016/j.foodres.2023.113226. Epub 2023 Jul 4.ABSTRACTHuangjiu is a traditional Chinese alcoholic beverage, whose non-volatile chemical profile remains unclarified. Here, the non-volatile compounds of Huangjiu were first identified using a widely targeted metabolomics analysis. In total, 1146 compounds were identified, 997 of them were identified in Huangjiu for the first time. Moreover, 113 compounds were identified as key active ingredients of traditional Chinese medicines and 78 components were found as active pharmaceutical ingredients against 389 diseases. In addition, the comparative analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that Huangjiu from different regions differ in metabolite composition. Cofactor and amino acid biosynthesis and ABC transport were the dominant metabolic pathways. Furthermore, 7 metabolic pathways and 77 metabolic pathway regulatory markers were further found to be related with the different characteristics of different Huangjius. This study provides a theoretical and material basis for the quality control, health efficacy, and industrial development of Huangjiu.PMID:37689963 | DOI:10.1016/j.foodres.2023.113226

Metagenomics and metabolomics of Toddy, an Indian fermented date palm beverage

Sun, 10/09/2023 - 12:00
Food Res Int. 2023 Oct;172:113205. doi: 10.1016/j.foodres.2023.113205. Epub 2023 Jun 29.ABSTRACTToddy is a popular fermented palm beverage of India. No scientific information on shotgun metagenomics and metabolomics are available on toddy of India till date. Hence, we choose the fermented date palm beverage, locally called khejur toddy, of West Bengal and Jharkhand states of India, to profile microbial community, their targeted and untargeted metabolites to study the putative bio-functional genes corresponding to regulatory metabolic pathways. Shotgun-based metataxonomic analyses revealed the existence of all domains where bacteria were the most abundant domain (94.48%) followed by eukaryotes (3.38%), viruses (1.53%) and archaea (0.61%). Overall, 54 phyla, 363 families, 1087 genera and 1885 species were observed and identified. Bacillota (49.3%) was the most abundant bacterial phylum. At species level, several species of bacteria and yeasts were detected in toddy samples which included Leuconostoc mesenteroides,Leuconostoc citreum,Lactobacillus helveticus,Lactiplantibacillus plantarum,Lactococcus lactis, Acetobacter malorum, Gluconobacter japonicus, Gluconacetobacter liquefaciens, Fructobacillus durionis, Zymomonas mobilis and yeastsSaccharomyces cerevisiae, Hanseniaspora uvarumandHanseniaspora guilliermondii. Toddy metagenome was also compared with metagenome of pulque, the Mexican fermented fresh sap ofAgave, which was retrieved from NCBI database, and also with metagenomic data of some amplicon-based previous studies on toddy and African fermented palm drink for similarity, dissimilarity and uniqueness among them. Predictive biosynthesis of ethanol, acetic acid, butanoate, linalool, staurosporine, prodigiosin, folic acid, riboflavin, etc. were annotated by KEGG/COG database. Clustered regularly interspaced short palindromic repeats (CRISPR) analysis detected 23 arrays (average length 23.69 bp ± 4.28). Comprehensive Antibiotic Resistance Database (CARD) analysis did not show the presence of any momentous antibiotic resistance gene among the major microbial members. Metabolomics analysis detected many primary and secondary metabolites. We believe this is the first report on complete shotgun metagenomics, and metabolomics of fermented palm drink of India as well as Eastern India.PMID:37689952 | DOI:10.1016/j.foodres.2023.113205

A comprehensive analytical framework integrating liquid chromatography-tandem mass spectrometry metabolomics with chemometrics for metabolite profiling of lettuce varieties and discovery of antibacterial agents

Sun, 10/09/2023 - 12:00
Food Res Int. 2023 Oct;172:113178. doi: 10.1016/j.foodres.2023.113178. Epub 2023 Jun 20.ABSTRACTThis study comprehensively characterized the metabolite profiles of six lettuce varieties and established the correlation between the elucidated profiles and their antivirulence effects. A total of 195 metabolites were annotated using LC-QTOF-MS/MS metabolomics assisted by molecular networking and integrated with chemometrics. Red varieties (red longifolia and lolla rosa) demonstrated higher chlorogenic and chicoric acids suggesting their antioxidant properties. In parallel, amino acids and disaccharides were enriched in romaine longifolia rationalizing its palatable taste and nutritional potential, while crispa, capitata, and lolla bionda presented a high β-carboline alkaloid content. The antibacterial and antihemolytic potential of all varieties against methicillin-sensitive and methicillin-resistant Staphylococcus aureus was assessed and validated by prominent downregulation of α-hemolysin transcriptional levels in both strains. Moreover, correlation analysis revealed sesquiterpenes, β-carboline alkaloids, amino acids, and oxy-fatty acids as the main bioactives. Results emphasize lettuce significance as a functional food and nutraceutical source, and highlight varieties naturally rich in antibacterial agents to adapt breeding programs.PMID:37689928 | DOI:10.1016/j.foodres.2023.113178

Comparative characterization of flavor precursors and volatiles of Taihe black-boned silky fowl and Hy-line Brown yolks using multiomics and GC-O-MS-based volatilomics

Sun, 10/09/2023 - 12:00
Food Res Int. 2023 Oct;172:113168. doi: 10.1016/j.foodres.2023.113168. Epub 2023 Jun 18.ABSTRACTEggs are nutritious and highly valued by consumers. However, egg flavor varies greatly among different hen breeds. The present study used gas chromatography-olfactometry-mass spectrometry-based volatilomics to identify and compare volatile compounds in Taihe black-boned silky fowl (TS) and Hy-line Brown (HL) egg yolks. In addition, the relationships between the levels of different metabolites and lipids and flavor-associated differences were investigated using multiomics. Twenty-eight odorants in total were identified; among them, the levels of 3-methyl-butanal, 1-octen-3-ol, 2-pentylfuran, and (E, E)-2,4-decadienal differed significantly (P < 0.05) between TS and HL egg yolks. The difference in flavor compounds results in TS egg yolks having a stronger overall odor and flavor and a higher acceptance level than HL egg yolks. Metabolomic analysis revealed that 112 metabolites in the egg yolks were significantly different between the two breeds. Furthermore, these different metabolites in the egg yolks of both breeds were significantly enriched in phenylalanine, tyrosine, and tryptophan biosynthesis pathways and phenylalanine metabolism, alanine, aspartate, and glutamate metabolism pathways (P < 0.05), as identified by both metabolite set enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Lipidomic analysis revealed significant differences in the lipid subclasses, lipid molecules, and fatty acid profiles between the egg yolks from the two breeds. As a result, 48 lipid molecules had variable influence in projection values > 1 based on the partial least squares regression model, which may play a role in the differences in aroma characteristics between the two breeds through oxidative degradation of fatty acids. Our study revealed the metabolite, lipid, and volatility profiles of TS and HL egg yolks and may provide an important basis for improving egg flavor to satisfy various consumer preferences.PMID:37689921 | DOI:10.1016/j.foodres.2023.113168

Pages