PubMed

Chemosphere. 2023 Sep 21:140219. doi: 10.1016/j.chemosphere.2023.140219. Online ahead of print.ABSTRACTRhizosphere phosphatases can exhibit hormetic effects in response to cadmium (Cd) ion stimulation. However, understanding the mechanisms underlying hormesis effects on soil ecosystems is challenging as studies on hormesis are usually specific to an organism, cell, or organ. To comprehensively investigate the mechanism of phosphatase hormesis, this study utilized in situ zymography and metabolomics to analyze the rhizosphere of Trifolium repens L. (white clover). Zymograms showed that rhizosphere phosphatase displayed a hormetic effect in 10 mg kg-1 Cd contaminated soil, with a hotspot area 1.8 times larger than non-Cd contaminated soil and a slight increase in enzyme activity. Nevertheless, the phosphatase activity was substantially suppressed upon elevating the Cd concentration in the soil to 50 mg kg-1. Differential metabolite identification and KEEG pathway enrichment analysis revealed that both rhizosphere organic acids and amino acid compounds positively affected phosphatase activity, and both were able to stabilize complexation with Cd ions via carboxyl groups. Besides, molecular docking models suggested that Cd ions act as cofactors to induce the formation of hydrogen bonds between amino acids/organic acids and phosphatase residues to form a triplet complex with a more stable structure, thereby improving phosphatase activity. The results indicated that amino acids and organic acids are heavily enriched in the rhizosphere of white clover and form a particular structure with soil Cd ions and phosphatase, which is essential for inducing the phosphatase hormesis as a detoxification mechanism in the rhizosphere micro-ecosystem.PMID:37741368 | DOI:10.1016/j.chemosphere.2023.140219

J Nutr Biochem. 2023 Sep 21:109448. doi: 10.1016/j.jnutbio.2023.109448. Online ahead of print.ABSTRACTMultiple sclerosis (MS) is a disease of the central nervous system that involves the immune system attacking the protective covering of nerve fibers. This disease can be influenced by both environmental and genetic factors. Evidence has highlighted the critical role of the intestinal microbiota in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). The composition of gut microflora is mainly determined by dietary components, which, in turn, modulate host homeostasis. A diet rich in naringenin at 0.5% can effectively mitigate the severity of EAE in mice. However, there is little direct data on the impact of naringenin at optimal doses on EAE development, as well as its intestinal microbiota and metabolites. Our study revealed that 2.0% naringenin resulted in the lowest clinical score and pathological changes in EAE mice, and altered the gene expression profiles associated with inflammation and immunity in spinal cord tissue. We then used untargeted metabolomics and 16S rRNA gene sequence to identify metabolites and intestinal microbiota, respectively. Naringenin supplementation enriched gut microbiota in EAE mice, including increasing the abundance of Paraprevotellaceae and Comamonadaceae, while decreasing the abundance of Deltaproteobacteria, RF39, and Desulfovibrionaceae. Furthermore, the changes in gut microbiota affected the production of metabolites in the feces and brain, suggesting a role in regulating the gut-brain axis. Finally, we conducted a fecal transplantation experiment to validate that gut microbiota partly mediates the effect of naringenin on EAE alleviation. In conclusion, naringenin has potential immunomodulatory effects that are influenced to some extent by the gut microbiome.PMID:37741298 | DOI:10.1016/j.jnutbio.2023.109448

Biomed Pharmacother. 2023 Sep 21;167:115531. doi: 10.1016/j.biopha.2023.115531. Online ahead of print.ABSTRACTBACKGROUND: Acute kidney injury (AKI) is a known complication of cisplatin administration; currently, there are no effective ways to prevent it. Therefore, it largely limited the use of cisplatin in chemotherapy in the clinic. In this study, we reported that Limonin, a triterpenoid compound extracted from citrus, alleviated cisplatin-induced AKI through metabolic reprogramming in the diseased kidneys.METHODS: Cisplatin was employed to induce AKI in mice. Three groups were set up: Sham, cisplatin + vehicle, and cisplatin + Limonin. Using UHPLC-TOF/MS, we conducted metabolomics to profile the kidneys' endogenous metabolites and metabolic pathways. A network pharmacological method was performed to identify the targets of Limonin on AKI. The human proximal tubular epithelial cell line (HK-2) was applied for in vitro studies.RESULTS: Limonin preserved serum creatinine and blood urea nitrogen levels after cisplatin-induced AKI. Employing metabolomics, we identified 33 endogenous differentially expressed metabolites and 7 significantly disturbed metabolic pathways in the diseased kidneys within three groups. After AKI, Limonin significantly reduced linoleic acid and its downstream product, arachidonic acid, thus exerting a protective effect on the kidney. The network pharmacological method identified CYP3A4 as a key target of Limonin in treating AKI, while CYP3A4 also serve as a mediator of arachidonic acid metabolism. In vitro, Limonin markedly reduced the level of arachidonic acid and HK-2 cell apoptosis triggered by cisplatin, mainly related to the targeted inhibition of CYP3A4-mediated arachidonic acid metabolism.CONCLUSION: Limonin ameliorates cisplatin-induced AKI by inhibiting CYP3A4 activity to regulate arachidonic acid metabolism, ultimately preserving kidney function.PMID:37741252 | DOI:10.1016/j.biopha.2023.115531

Food Chem. 2023 Sep 7;434:137372. doi: 10.1016/j.foodchem.2023.137372. Online ahead of print.ABSTRACTThe effect of steaming treatment on salmon quality was explored by different multi-omics and electronic sensory system in this study. A comparison between conventional steaming (CS) and anaerobic steaming (AS) was conducted in organoleptic quality of salmon. Twelve key volatile compounds were identified, which contributed to the flavor difference. The concentrations of hexanal, (E)-2-octen-1-al, and decanal in AS salmon were significantly lower than in CS salmon, which account for 68.9-80.5 % of the latter. During steaming, the fatty acids and diacylglycerols decreased significantly by 37.4 % and 57.9 %, respectively. Anaerobic steaming limited the degradation of some oxidized lipids, further reduced some volatile secondary oxidation products. Nucleotides and derivatives, succinic acid, glutamic acid, hydroxyproline and betaine contributed to the saltness, umami, richness of steamed salmon. Metabolomics data revealed that the higher creatinine, Ala-Ala and Ala-Leu provided more umami and less bitterness to AS salmon.PMID:37741235 | DOI:10.1016/j.foodchem.2023.137372

Virology. 2023 Aug 19;587:109866. doi: 10.1016/j.virol.2023.109866. Online ahead of print.ABSTRACTWe previously reported the discovery and characterization of two novel proteins (ORF1 and ORF2) generated by the alternative splicing of the JC virus (JCV) late coding region. Here, we report the discovery and partial characterization of three additional novel ORFs from the same coding region, ORF3, ORF4 and ORF5, which potentially encode 70, 173 and 265 amino acid long proteins respectively. While ORF3 protein exhibits a uniform distribution pattern throughout the cells, we were unable to detect ORF5 expression. Surprisingly, ORF4 protein was determined to be the only JCV protein specifically targeting the promyelocytic leukemia nuclear bodies (PML-NBs) and inducing their reorganization in nucleus. Although ORF4 protein has a modest effect on JCV replication, it is implicated to play major roles during the JCV life cycle, perhaps by regulating the antiviral response of PML-NBs against JCV infections and thus facilitating the progression of the JCV-induced disease in infected individuals.PMID:37741199 | DOI:10.1016/j.virol.2023.109866

J Plant Physiol. 2023 Sep 16;289:154095. doi: 10.1016/j.jplph.2023.154095. Online ahead of print.ABSTRACTFew studies have been conducted to investigate the impact of pesticides on the secondary metabolism of traditional Chinese medicine and strategies to mitigate the toxicity of pesticide-induced oxidative stress. The current study focuses on evaluating the potential impacts of nano selenium (NSe) and imidacloprid (IMI) on the quality, physiological biochemistry, and secondary metabolites in Perilla frutescens (L.) Britt. (P. frutescens). The study utilized metabolome analysis to explore the toxicity mechanism of IMI. The study noted that IMI-induced stress could emerge with detrimental effects by targeting the destruction of the phenylpropanoid biosynthesis pathway. IMI-induced phenylpropanoid metabolism disorder resulted in an 8%, 17%, 25%, 10%, 65%, and 29% reduction in phenylalanine, coniferyl aldehyde, ferulic acid, cafestol, p-coumaraldehyde, and p-coumaric acid levels, respectively. Under the treatment of exogenous NSe, the levels of these metabolites were increased by 16%, 32%, 22%, 22%, 92%, and 29%, respectively. The application of exogenous NSe increased the levels of these metabolites and improved the biochemical disorder and quality of P. frutescens leaves by optimizing the phenylpropanoid metabolic pathway and enhancing the antioxidant system. Overall, the results suggest that foliar application of NSe could alleviate the oxidative stress toxicity induced by IMI and improve the quality of P. frutescens.PMID:37741053 | DOI:10.1016/j.jplph.2023.154095

Redox Biol. 2023 Sep 19;67:102889. doi: 10.1016/j.redox.2023.102889. Online ahead of print.ABSTRACTMaternal diets during pregnancy and lactation are key determinants that regulate the development of metabolic syndrome (MetS) in offspring. l-malic acid (MA) was previously reported to improve antioxidant capacity and aerobic metabolism. However, the effects of maternal MA consumption on the metabolic features of offspring remain largely unexplored. Herein, through pig models consuming MA-enriched diets during late pregnancy and lactation, we found that maternal MA consumption potentiated the anti-inflammatory and antioxidant capacity of sows, thereby improving their reproductive performance and the growth performance of piglets. Maternal MA consumption also induced a transition of slow-twitch to fast-twitch fibers in the early life of offspring. Along with muscle growth and fiber-type transition, insulin sensitivity and glucose metabolism, including aerobic metabolism and glycolysis, were improved in the skeletal muscle of offspring. An untargeted metabolomic analysis further revealed the contribution of modified amino acid metabolism to the improved aerobic metabolism. Mechanistically, maternal MA consumption remodeled colonic microbiota of their offspring. Briefly, the abundance of Colidextribacter, Romboutsia, and Family_XIII_AD3011_group increased, which were positively associated with the antioxidant capacity and glucose metabolism of skeletal muscles. A decreased abundance of Prevotella, Blautia, Prevotellaceae_NK3B31_group, and Collinsella was also detected, which were involved in less insulin sensitivity. Notably, milk metabolites, such as ascorbic acid (AA) and granisetron (GS), were found as key effectors regulating the gut microbiota composition of piglets. The properties of AA and GS in alleviating insulin resistance, inflammation, and oxidative stress were further verified through mice treated with high-fat diets. Overall, this study revealed that maternal MA consumption could modulate the inflammatory response, antioxidant capacity, and glucose metabolism by regulating the gut microbiota of offspring through the vertical transmission of milk metabolites. These findings suggest the potential of MA in the prevention and treatment of MetS in early life.PMID:37741046 | DOI:10.1016/j.redox.2023.102889

Environ Int. 2023 Sep 16;180:108215. doi: 10.1016/j.envint.2023.108215. Online ahead of print.ABSTRACTRhizoremediation is a promising remediation technology for the removal of soil persistent organic pollutants (POPs), especially benzo[a]pyrene (BaP). However, our understanding of the associations among rhizospheric soil metabolites, functional microorganisms, and POPs degradation in different plant growth stages is limited. We combined stable-isotope probing (SIP), high-throughput sequencing, and metabolomics to analyze changes in rhizospheric soil metabolites, functional microbes, and BaP biodegradation in the early growth stages (tillering, jointing) and later stage (booting) of ryegrass. Microbial community structures differed significantly among growth stages. Metabolisms such as benzenoids and carboxylic acids tended to be enriched in the early growth stage, while lipids and organic heterocyclic compounds dominated in the later stage. From SIP, eight BaP-degrading microbes were identified, and most of which such as Ilumatobacter and Singulisphaera were first linked with BaP biodegradation. Notably, the relationship between the differential metabolites and BaP degradation efficiency further suggested that BaP-degrading microbes might metabolize BaP directly to produce benzenoid metabolites (3-hydroxybenzo[a]pyrene), or utilize benzenoids (phyllodulcin) to stimulate the co-metabolism of BaP in early growth stage; some lipids and organic acids, e.g. 1-aminocyclopropane-1-carboxylic acid, might provide nutrients for the degraders to promote BaP metabolism in later stage. Accordingly, we determined that certain rhizospheric metabolites might regulate the rhizospheric microbial communities at different growth stages, and shift the composition and diversity of BaP-degrading bacteria, thereby enhancing in situ BaP degradation. Our study sheds light on POPs rhizoremediation mechanisms in petroleum-contaminated soils.PMID:37741005 | DOI:10.1016/j.envint.2023.108215

J Sci Food Agric. 2023 Sep 23. doi: 10.1002/jsfa.13002. Online ahead of print.ABSTRACTBACKGROUND: Lianhua-Qingwen (LHQW) capsule is a Traditional Chinese Medicine (TCM) formula having anti-viral and anti-inflammatory activities. During the capsule production, huge byproducts will be yielded and disposed as waste by burying. Resourceful utilization of this kind of TCM byproducts as feed additives through stage-based co-fermentation using enzyme and probiotics could reduce environmental stress and resource shortage. The in vitro characterization and the supplementary effects of the fermented TCM byproducts (FTCM) for weaned piglets (initial body weight, 7.23 ± 0.33 kg; dose: basal diet + 300 mg/kg FTCM) were investigated.RESULTS: Higher reducing sugar content, total flavonoid content, flavonoid compounds (e.g. tectoridin, tricetin, flavone, apigenin, naringenin), and total antioxidant activity were determined in the FTCM compared to the spontaneously fermented and unfermented materials. Supplementation of the FTCM to piglets did not significantly affect the feed intake, body weight gain, and feed/gain ratio, but significantly decreased a pro-inflammatory cytokine IL-8 and increased intestinal total antioxidant activity (TAC) and superoxide dismutase (SOD) activity. Moreover, FTCM supplementation increased α-diversity of the colonic microbiota accompanied with increased abundance of Prevotella genus and Treponema berlinense species. Correlation analysis indicates T. berlinense is responsible for the decreased IL-8 level and enhanced intestinal TAC and SOD activities which might be mediated by a homoserine lactone molecule (3-oxo-C14).CONCLUSION: Overall, the stepwise co-fermentation enriched bioactive compounds within the TCM byproducts and its dietary supplementation did not generate any side effect on growth performance but displayed beneficial effects on enrichment of potential probiotic T. berlinense and relevant functions. This article is protected by copyright. All rights reserved.PMID:37740928 | DOI:10.1002/jsfa.13002

Eur Radiol. 2023 Sep 23. doi: 10.1007/s00330-023-10138-9. Online ahead of print.ABSTRACTOBJECTIVES: The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors prioritizes isocitrate dehydrogenase (IDH) mutation to define tumor types in diffuse gliomas, in contrast to the 2016 classification, which prioritized histological features. Our objective was to investigate the influence of this change in the performance of proton MR spectroscopy (1H-MRS) in segregating high-grade diffuse astrocytoma subgroups.METHODS: Patients with CNS WHO grade 3 and 4 diffuse astrocytoma, known IDH mutation status, and available 1H-MRS were retrospectively retrieved and divided into 4 groups based on IDH mutation status and histological grade. Differences in 1H-MRS between groups were analyzed with the Kruskal-Wallis test. The points on the spectrum that showed the greatest differences were chosen to evaluate the performance of 1H-MRS in discriminating between grades 3 and 4 tumors (WHO 2016 defined), and between IDH-mutant and IDH-wildtype tumors (WHO 2021). ROC curves were constructed with these points, and AUC values were calculated and compared.RESULTS: The study included 223 patients with high-grade diffuse astrocytoma. Discrimination between IDH-mutant and IDH-wildtype tumors showed higher AUC values (highest AUC short TE, 0.943; long TE, 0.864) and more noticeable visual differences than the discrimination between grade 3 and 4 tumors (short TE, 0.885; long TE, 0.838).CONCLUSION: Our findings suggest that 1H-MRS is more applicable to classify high-grade astrocytomas defined with the 2021 criteria. Improved metabolomic robustness and more homogeneous groups yielded better tumor type discrimination by 1H-MRS with the new criteria.CLINICAL RELEVANCE STATEMENT: The 2021 World Health Organization classification of brain tumors empowers molecular criteria to improve tumor characterization. This derives in greater segregation of high-grade diffuse astrocytoma subgroups by MR spectroscopy and warrants further development of brain tumor classification tools with spectroscopy.KEY POINTS: • The new 2021 updated World Health Organization classification of central nervous system tumors maximizes the role of molecular diagnosis in the classification of brain tumors. • Proton MR spectroscopy performs better to segregate high-grade astrocytoma subgroups when defined with the new criteria. • The study provides additional evidence of improved metabolic characterization of brain tumor subgroups with the new criteria.PMID:37740778 | DOI:10.1007/s00330-023-10138-9

Metabolomics. 2023 Sep 23;19(10):85. doi: 10.1007/s11306-023-02047-1.ABSTRACTINTRODUCTION: Modern comprehensive instrumentations provide an unprecedented coverage of complex matrices in the form of high-dimensional, information rich data sets.OBJECTIVES: In addition to the usual biomarker research that focuses on the detection of the studied condition, we aimed to define a proper strategy to conduct a correlation analysis on an untargeted colorectal cancer case study with a data set of 102 variables corresponding to metabolites obtained from serum samples analyzed with comprehensive two-dimensional gas chromatography coupled to high-resolution time-of-flight mass spectrometry (GC × GC-HRTOF-MS). Indeed, the strength of association existing between the metabolites contains potentially valuable information about the molecular mechanisms involved and the underlying metabolic network associated to a global perturbation, at no additional analytical effort.METHODS: Following Anscombe's quartet, we took particular attention to four main aspects. First, the presence of non-linear relationships through the comparison of parametric and non-parametric correlation coefficients: Pearson's r, Spearman's rho, Kendall's tau and Goodman-Kruskal's gamma. Second, the visual control of the detected associations through scatterplots and their associated regressions and angles. Third, the effect and handling of atypical samples and values. Fourth, the role of the precision of the data on the attribution of the ranks through the presence of ties.RESULTS: Kendall's tau was found the method of choice for the data set at hand. Its application highlighted 17 correlations significantly altered in the active state of colorectal cancer (CRC) in comparison to matched healthy controls (HC), from which 10 were specific to this state in comparison to the remission one (R-CRC) investigated on distinct patients. 15 metabolites involved in the correlations of interest, on the 25 unique ones obtained, were annotated (Metabolomics Standards Initiative level 2).CONCLUSIONS: The metabolites highlighted could be used to better understand the pathology. The systematic investigation of the methodological aspects that we expose allows to implement correlation analysis to various fields and many specific cases.PMID:37740774 | DOI:10.1007/s11306-023-02047-1

Hum Reprod. 2023 Sep 22:dead189. doi: 10.1093/humrep/dead189. Online ahead of print.ABSTRACTSTUDY QUESTION: What metabolic pathways and metabolites in the serum and follicular fluid are associated with peak estradiol levels and the number of mature oocytes?SUMMARY ANSWER: In the serum metabolome, mostly fatty acid and amino acid pathways were associated with estradiol levels and mature oocytes while in the follicular fluid metabolome, mostly lipid, vitamin, and hormone pathways were associated with peak estradiol levels and mature oocytes.WHAT IS KNOWN ALREADY: Metabolomics has identified several metabolic pathways and metabolites associated with infertility but limited data are available for ovarian stimulation outcomes.STUDY DESIGN, SIZE, DURATION: A prospective cohort study of women undergoing IVF from 2009 to 2015.PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 125 women undergoing a fresh IVF cycle at a fertility clinic in the Northeast United States who provided a serum and follicular fluid sample. Untargeted metabolomics profiling was conducted using liquid chromatography with high-resolution mass spectrometry in two chromatography columns (C18 and hydrophilic interaction chromatography (HILIC)). The main ovarian stimulation outcomes were peak serum estradiol levels and number of mature oocytes. We utilized adjusted generalized linear regression models to identify significant metabolic features. Models were adjusted for age,BMI, initial infertility diagnosis, and ovarian stimulation protocol. We then conducted pathway analysis using mummichog and metabolite annotation using level-1 evidence.MAIN RESULTS AND ROLE OF CHANCE: In the serum metabolome, 480 and 850 features were associated with peak estradiol levels in the C18 and HILIC columns, respectively. Additionally, 437 and 538 features were associated with mature oocytes in the C18 and HILIC columns, respectively. In the follicular fluid metabolome, 752 and 929 features were associated with peak estradiol levels in the C18 and HILIC columns, respectively, Additionally, 993 and 986 features were associated with mature oocytes in the C18 and HILIC columns, respectively. The most common pathways associated with peak estradiol included fatty acids (serum and follicular fluid), hormone (follicular fluid), and lipid pathways (follicular fluid). The most common pathways associated with the number of mature oocytes retrieved included amino acids (serum), fatty acids (serum and follicular fluid), hormone (follicular fluid), and vitamin pathways(follicular fluid). The vitamin D3 pathway had the strongest association with both ovarian stimulation outcomes in the follicularfluid. Four and nine metabolites were identified using level-1 evidence (validated identification) in the serum and follicular fluid metabolomes, respectively.LIMITATIONS, REASONS FOR CAUTION: Our sample was majority White and highly educated and may not be generalizable to thewider population. Additionally, residual confounding is possible and the flushing medium used in the follicular fluid could have diluted our results.WIDER IMPLICATIONS OF THE FINDINGS: The pathways and metabolites identified by our study provide novel insights into the biologicalmechanisms in the serum and follicular fluid that may underlie follicular and oocyte development, which could potentially be used to improve ovarian stimulation outcomes.STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the following grants from the National Institute of Environmental Health Sciences (P30-ES019776, R01-ES009718, R01-ES022955, P30-ES000002, R00-ES026648, and T32-ES012870), and National Institute of Diabetes and Digestive and Kidney Diseases (P30DK046200). The authors have no competing interests to disclose.TRIAL REGISTRATION NUMBER: N/A.PMID:37740688 | DOI:10.1093/humrep/dead189

J Infect Dis. 2023 Sep 22:jiad410. doi: 10.1093/infdis/jiad410. Online ahead of print.ABSTRACTBACKGROUND: High resolution metabolomics (HRM) is an innovative tool to study challenging infectious diseases like leprosy, where the pathogen cannot be grown with standard methods. Here, we use HRM to better understand associations between disease manifestations, nutrition, and host metabolism.METHODS: From 2018-2019, adults with leprosy and controls were recruited in Minas Gerais, Brazil. Plasma metabolites were detected using an established HRM workflow and characterized by accurate mass m/z and retention time. The mummichog informatics package compared metabolic pathways between cases and controls and between multibacillary (MB) and paucibacillary (PB) leprosy. Additionally, select individual metabolites were quantified and compared.RESULTS: Thirty-nine cases (62% MB and 38% PB) and 25 controls were enrolled. We found differences (p<0.05) in several metabolic pathways, including fatty acid metabolism, carnitine shuttle, retinol, vitamin D3, and C-21 steroid metabolism between cases and controls with lower retinol and associated metabolites in cases. Between MB and PB, leukotrienes, prostaglandins, tryptophan, and cortisol were all found to be lower in MB (p<0.05).DISCUSSION: Metabolites associated with several nutrient-related metabolic pathways appeared differentially regulated in leprosy, especially MB vs PB. This pilot study demonstrates the metabolic interdependency of these pathways, which may play a role in the pathophysiology of disease.PMID:37740551 | DOI:10.1093/infdis/jiad410

Food Funct. 2023 Sep 22. doi: 10.1039/d3fo01770b. Online ahead of print.ABSTRACTThe study of all chemical processes involving metabolites is known as metabolomics. It has been developed into an essential tool in several disciplines, such as the study of plant physiology, drug development, human diseases, and nutrition. The field of food science, diagnostic biomarker research, etiological analysis in the field of medical therapy, and raw material quality, processing, and safety have all benefited from the use of metabolomics recently. Food metabolomics includes the use of metabolomics in food production, processing, and human diets. As a result of changing consumer habits and the rising of food industries all over the world, there is a remarkable increase in interest in food quality and safety. It requires the employment of various technologies for the food supply chain, processing of food, and even plant breeding. This can be achieved by understanding the metabolome of food, including its biochemistry and composition. Additionally, Food metabolomics can be used to determine the similarities and differences across crop kinds, as an indicator for tracking the process of ripening to increase crops' shelf life and attractiveness, and identifying metabolites linked to pathways responsible for postharvest disorders. Moreover, nutritional metabolomics is used to investigate the connection between diet and human health through detection of certain biomarkers. This review assessed and compiled literature on food metabolomics research with an emphasis on metabolite extraction, detection, and data processing as well as its applications to the study of food nutrition, food-based illness, and phytochemical analysis. Several studies have been published on the applications of metabolomics in food but further research concerning the use of standard reproducible procedures must be done. The results published showed promising uses in the food industry in many areas such as food production, processing, and human diets. Finally, metabolome-wide association studies (MWASs) could also be a useful predictor to detect the connection between certain diseases and low molecular weight biomarkers.PMID:37740352 | DOI:10.1039/d3fo01770b

Nat Commun. 2023 Sep 22;14(1):5923. doi: 10.1038/s41467-023-41629-4.ABSTRACTTreatment of osteoporosis commonly diminishes osteoclast number which suppresses bone formation thus compromising fracture prevention. Bone formation is not suppressed, however, when bone degradation is reduced by retarding osteoclast functional resorptive capacity, rather than differentiation. We find deletion of deubiquitinase, BRCA1-associated protein 1 (Bap1), in myeloid cells (Bap1∆LysM), arrests osteoclast function but not formation. Bap1∆LysM osteoclasts fail to organize their cytoskeleton which is essential for bone degradation consequently increasing bone mass in both male and female mice. The deubiquitinase activity of BAP1 modifies osteoclast function by metabolic reprogramming. Bap1 deficient osteoclast upregulate the cystine transporter, Slc7a11, by enhanced H2Aub occupancy of its promoter. SLC7A11 controls cellular reactive oxygen species levels and redirects the mitochondrial metabolites away from the tricarboxylic acid cycle, both being necessary for osteoclast function. Thus, in osteoclasts BAP1 appears to regulate the epigenetic-metabolic axis and is a potential target to reduce bone degradation while maintaining osteogenesis in osteoporotic patients.PMID:37740028 | DOI:10.1038/s41467-023-41629-4

Clin Nutr ESPEN. 2023 Oct;57:617-623. doi: 10.1016/j.clnesp.2023.08.012. Epub 2023 Aug 14.ABSTRACTBACKGROUND: During Intensive Care Unit (ICU) admission, patients demonstrate up to 15% muscle loss per week, contributing to neuromuscular weakness, complicating recovery and delaying return to daily life. Biomarkers for muscle loss could aid in early detection of patients at risk and help guide resources to mitigate muscle loss, e.g. physical therapy and protein supplementation.AIMS: To explore serum biomarkers for muscle mass and muscle loss in ICU patients using a metabolomics approach.METHODS: Mechanically ventilated patients with an unplanned ICU admission between June and December 2021 were prospectively studied. The cross-sectional area of the rectus femoris muscle was assessed using ultrasound (RFcsa) and 188 serum metabolites were assessed using the Biocrates™ AbsoluteIDQ p180 kit for targeted metabolomics. Patients were eligible for analysis when a serum sample drawn within 5 days of ICU admission and at least 1 RFcsa were available. In patients with sequential RFcsa measurements, muscle loss was defined as the negative slope of the regression line fitted to the RFcsa measurements per patient in the first 10 days of ICU admission. Correlations between baseline metabolite concentrations and baseline muscle mass, as well as between baseline metabolite concentrations and muscle loss were assessed using Pearson's test for correlations. To correct for multiple testing, the Benjamini-Hochberg procedure was used.RESULTS: Seventeen patients were eligible for analysis. Mean age was 62 (SD ± 9) years and the cohort was predominantly male (76%). Four metabolites correlated with baseline muscle mass: creatinine (R = 0.5, p = 0.041), glycerophospholipid PC_ae_C30_0 (R = 0.5, p = 0.034) and two acylcarnitines: C14_2 (R = 0.5, p = 0.042) and C10_2 (R = 0.5, p = 0.049). For muscle loss, significant associations were found for histidine (R = -0.8, p = 0.002) and three glycerophospholipids; PC_aa_C40_2 (R = 0.7, p = 0.015), PC_ae_C40_1 (R = 0.6, p = 0.032) and PC_aa_C42_1 (R = 0.6, p = 0.037). After correction for multiple testing, no significant associations remained.CONCLUSIONS: This exploratory analysis found certain metabolites to be associated with muscle mass and muscle loss. Future research, specifically addressing these metabolites is necessary to confirm or refute an association with muscle loss and determine their role as potential muscle loss marker.PMID:37739714 | DOI:10.1016/j.clnesp.2023.08.012

Clin Nutr ESPEN. 2023 Oct;57:21-28. doi: 10.1016/j.clnesp.2023.06.005. Epub 2023 Jun 13.ABSTRACTBACKGROUND & AIMS: Metabolic biomarkers with pathophysiological relevance is lacking in pediatric diabetes. We aimed to identify novel metabolic biomarkers in pediatric type 1 (T1D) and type 2 diabetes (T2D). We hypothesized that (1) targeted plasma metabolomics, focused on plasma amino acid concentrations, could identify distinctively altered patterns in children with T1D or T2D, and (2) there are specific changes in concentrations of metabolites related to branch chain amino acids (BCAA) and arginine metabolism in children with T2D.METHODS: In a pilot study, we enrolled children with T1D (n = 15) and T2D (n = 13), and healthy controls (n = 15). Fasting plasma amino acid concentrations were measured by ultra-performance liquid chromatography, and compared between the groups after adjustment for confounding factors.RESULTS: The mean age (SD) of participants was 16.4 (0.9) years. There were no group differences in age, gender, race/ethnicity, or 24-h protein intake. Mean BMI percentile was higher in the T2D than the T1D group or controls (p < 0.001). The T2D group had lower arginine, citrulline, glutamine, glycine, phenylalanine, methionine, threonine, asparagine and symmetric dimethylarginine (SDMA) but higher aspartate than controls, after adjusting for BMI percentiles (all p < 0.05). Children with T2D also had lower glycine but higher ornithine, proline, leucine, isoleucine, valine, total BCAA, lysine and tyrosine than those with T1D after adjusting for confounding factors (all p < 0.05). Children with T1D had lower phenylalanine, methionine, threonine, glutamine, tyrosine, asymmetric dimethylarginine (ADMA) and SDMA than controls (all p < 0.05).CONCLUSIONS: Children with T2D and T1D have distinct fasting plasma amino acid signatures that suggest varying pathogenic mechanisms and could serve as biomarkers for these conditions.PMID:37739658 | DOI:10.1016/j.clnesp.2023.06.005

Joint Bone Spine. 2023 Sep 20:105640. doi: 10.1016/j.jbspin.2023.105640. Online ahead of print.ABSTRACTRecent discoveries reveal that the chronic presence of senescent cells in osteoarticular tissues provides a focal point of disease development for osteoarthritis (OA). Nevertheless, senescence-regulatory factors associated with OA still need to be identified. Furthermore, few diagnostic- and prognostic-validated biochemical markers (biomarkers) are currently used in clinics to evaluate OA patients. In the future, alongside imaging and clinical examination, detecting senescence-regulatory biomarkers in patient fluids could become a prospective method for disease: diagnosis, monitoring, progression and prognosis following treatment. This review summarizes a group of circulating OA biomarkers recently linked to senescence onset. Remarkably, these factors identified in proteomics, metabolomic and microRNA studies could also have deleterious or protective roles in osteoarticular tissue homeostasis. In addition, we discuss their potentially innovative modulation in combination with senotherapeutic approaches, for long-lasting OA treatment.PMID:37739212 | DOI:10.1016/j.jbspin.2023.105640

Phytomedicine. 2023 Sep 2;121:155054. doi: 10.1016/j.phymed.2023.155054. Online ahead of print.ABSTRACTBACKGROUND: Tripterygium wilfordii has been widely used for the treatment of rheumatoid arthritis, which is frequently accompanied by severe gastrointestinal damage. The molecular mechanism underlying the gastrointestinal injury of Tripterygium wilfordii are yet to be elucidated.METHODS: Transmission electron microscopy, and pathological and biochemical analyses were applied to assess intestinal bleeding. Metabolic changes in the serum and intestine were determined by metabolomics. In vivo (time-dependent effect and dose-response) and in vitro (double luciferase reporter gene system, DRATs, molecular docking, HepG2 cells and small intestinal organoids) studies were used to identify the inhibitory role of celastrol on intestinal farnesoid X receptor (FXR) signaling. Fxr-knockout mice and FXR inhibitors and agonists were used to evaluate the role of FXR in the intestinal bleeding induced by Tripterygium wilfordii.RESULTS: Co-treatment with triptolide + celastrol (from Tripterygium wilfordii) induced intestinal bleeding in mice. Metabolomic analysis indicated that celastrol suppressed intestinal FXR signaling, and further molecular studies revealed that celastrol was a novel intestinal FXR antagonist. In Fxr-knockout mice or the wild-type mice pre-treated with pharmacological inhibitors of FXR, triptolide alone could activate the duodenal JNK pathway and induce intestinal bleeding, which recapitulated the pathogenic features obtained by co-treatment with triptolide and celastrol. Lastly, intestinal bleeding induced by co-treatment with triptolide and celastrol could be effectively attenuated by the FXR or gut-restricted FXR agonist through downregulation of the duodenal JNK pathway.CONCLUSIONS: The synergistic effect between triptolide and celastrol contributed to the gastrointestinal injury induced by Tripterygium wilfordii via dysregulation of the FXR-JNK axis, suggesting that celastrol should be included in the quality standards system for evaluation of Tripterygium wilfordii preparations. Determining the mechanism of the FXR-JNK axis in intestinal bleeding could aid in the identification of additional therapeutic targets for the treatment of gastrointestinal hemorrhage diseases. This study also provides a new standard for the quality assessment of Tripterygium wilfordii used in the treatment of gastrointestinal disorders.PMID:37738906 | DOI:10.1016/j.phymed.2023.155054

J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Sep 16;1229:123889. doi: 10.1016/j.jchromb.2023.123889. Online ahead of print.ABSTRACTQingxue Bawei (QXBW) tablets, a Mongolian medicine prescription, have proved to possess good lipid-lowering and antihypertensive effects in previous studies. However, the therapeutic effects and potential mechanisms of QXBW tablets on atherosclerosis (AS) have not been well studied yet. This study aimed to investigate the potential liver-protective mechanism of QXBW tablets on AS mice by hepatic lipidomics analysis. After 10 weeks of administration, serum and liver were collected for biochemical, histopathological, and lipid metabolomics analysis to evaluate the efficacy of the QXBW tablets on high-fat diet (HFD) induced mice. The experimental results indicated that QXBW tablets could ameliorate liver injury and inflammatory response in AS mice. Liver lipid data from different groups of mice were collected by UPLC-Q-Orbitrap-MS, and a total of 22 potential biomarkers with significant differences between the model and control groups were identified finally, of which 16 potential biomarkers were back-regulated after the QXBW tablets intervention. These 22 potential differential metabolic markers were mainly involved in glycerolipid metabolism, glycerophospholipid metabolism, and cholesterol ester metabolism pathways. The results of this study showed that serum inflammatory factors, liver function indices, and lipid metabolism disorders were positively alleviated in AS mice after QXBW tablets treatment.PMID:37738809 | DOI:10.1016/j.jchromb.2023.123889