PubMed

Environ Sci Technol. 2023 Jun 1. doi: 10.1021/acs.est.2c09737. Online ahead of print.ABSTRACTOur understanding is limited concerning the interaction mechanism between widespread phthalate esters and staple crops, which have strong implications for human exposure. Therefore, this study was aimed at illuminating the transformation pathways of di-n-butyl phthalate (DnBP) in rice using an untargeted screening method. UPLC-QTOF-MS identified 16 intermediate transformation products formed through hydroxylation, hydrolysis, and oxidation in phase I metabolism and further by conjugation with amino acids, glutathione, and carbohydrates in phase II metabolism. Mono-2-hydroxy-n-butyl phthalate-l-aspartic acid (MHBP-asp) and mono-2-hydroxy-n-butyl phthalate-d-alanyl-β-d-glucoside (MHBP-ala-glu) products were observed for the first time. The proteomic analysis demonstrated that DnBP upregulated the expression of rice proteins associated with transporter activity, antioxidant synthesis, and oxidative stress response and downregulated that of proteins involved in photosynthesis, photorespiration, chlorophyll binding, and mono-oxygenase activity. Molecular docking revealed that DnBP can affect protein molecular activity via pi-sigma, pi-alkyl, and pi-pi interactions or by forming carbon-hydrogen bonds. The metabolomic analysis showed that key metabolic pathways including citrate cycle, biosynthesis of aminoacyl-tRNA, and metabolism of amino acids, sphingolipids, carbohydrates, nucleotides, and glutathione were activated in rice plants exposed to DnBP and its primary metabolite mono-n-butyl phthalate (MnBP). Furthermore, exposure to 80 ng/mL MnBP significantly perturbed the metabolic profile and molecular function in plants, with downregulation of the levels of beta-alanine (0.56-fold), cytosine (0.48-fold), thymine (0.62-fold), uracil (0.48-fold), glucose (0.59-fold), and glucose-1-phosphate (0.33-fold), as well as upregulation of the levels of l-glutamic acid (2.97-fold), l-cystine (2.69-fold), and phytosphingosine (38.38-fold). Therefore, the degradation intermediates of DnBP pose a potentially risk to plant metabolism and raise concerns for crop safety related to plasticizer pollution.PMID:37260373 | DOI:10.1021/acs.est.2c09737

Integr Zool. 2023 Jun 1. doi: 10.1111/1749-4877.12734. Online ahead of print.ABSTRACTHerbivory is common in mammals, yet our understanding of detoxification processes used by mammals to biotransform plant secondary compounds (PSCs) is limited. Specialist herbivores are thought to have evolved detoxification mechanisms that rely more heavily on energetically cheap Phase I biotransformation reactions to process high levels of PSCs in their diets. We explored this hypothesis by comparing the urinary metabolite patterns of two specialist herbivores (genus Neotoma). Neotoma stephensi is an obligate specialist on one-seeded juniper (Juniperus monosperma). Neotoma lepida is a generalist forager across its range, yet populations in the Great Basin specialize on Utah juniper (J. osteosperma). While both juniper species have high levels of terpenes, the terpene profiles and quantities differ between the two. Individuals from both woodrat species were fed diets of each juniper in a cross-over design. Urine, collected over a 24-h period, was extracted and analyzed in an untargeted metabolomics approach using both GC-MS and HPLC-MS/MS. The obligate specialist N. stephensi excreted a unique pattern of Phase I metabolites when fed its native juniper, while N. lepida excreted a unique pattern of Phase II metabolites when fed its native juniper. Both woodrat species utilized the Phase II metabolic pathway of glucuronidation more heavily when consuming the more chemically diverse J. osteosperma, and N. stephensi utilized less glucuronidation than N. lepida when consuming J. monosperma. These results are consistent with the hypothesis that obligate specialists may have evolved unique and efficient biotransformation mechanisms for dealing with PSCs in their diet.PMID:37260156 | DOI:10.1111/1749-4877.12734

Cancer Med. 2023 Jun 1. doi: 10.1002/cam4.6194. Online ahead of print.ABSTRACTBACKGROUND: Gut microbiota plays a significant role in the colorectal cancer (CRC) process. Ectopic colonization of multiple oral bacteria is reportedly associated with CRC pathogenesis and progression, but the details remain unclear.METHODS: We enrolled a cohort of 50 CRC patients and 52 healthy controls from an East China population. Taxonomic and functional analysis of the fecal microbiota were performed using 16S rDNA (50 + 52 samples) and shotgun metagenomic sequencing (8 + 6 samples), respectively, with particular attention paid to gut-colonized oral bacteria.RESULTS AND CONCLUSIONS: The results showed more detected bacterial species but lower species evenness within the samples from CRC patients. To determine the specific bacteria enriched in each group, we analyzed their possible protective, carcinogenic, or opportunistic roles in the CRC process. Among the ectopic oral bacteria, we observed a significant increase in the abundance of Fusobacterium and decreased abundance of Prevotella and Ruminococcus in the CRC group. Main differences in the functional composition of these two groups were related to energy metabolism and biosynthesis, especially the glycolytic pathway. Furthermore, we validated the colonization of Fusobacterium nucleatum subsp. animalis within CRC tissues and studied its impact on the host intestinal epithelium and tumor cells. With high selectivity for cancerous tissues, this subspecies promoted CRC cell proliferation and induced potential DNA damage.PMID:37260140 | DOI:10.1002/cam4.6194

Anal Chem. 2023 Jun 1. doi: 10.1021/acs.analchem.2c04632. Online ahead of print.ABSTRACTUntargeted metabolomics is a powerful tool for investigating chemistry of complex biological systems, but its utility is compromised by the presence of uninformative features and the limited efficiency of currently available prioritization tools. More effective filtering and prioritization tools are required to address the challenges of large untargeted metabolomics datasets. Here, we introduce Metabolomics Peak Analysis Computational Tool (MPACT), a new mass spectrometry data analysis platform employing filtering based on multiple modalities, statistical techniques incorporating multilevel replication, and interactive data visualization. We demonstrate application of MPACT to uncover hidden effects of the rare earth element cerium on tunicate-associated bacterium Streptomyces sp. PTY087I2, culminating in characterization of two thiolated compounds including a new cysteine derivative, granaticin C, and granaticin D, recently described as mycothiogranaticin A. While we demonstrate application of MPACT to microbial natural products discovery using an elicitation approach, the platform should be readily adaptable to investigation of multipartite interactions, biomarker detection, small molecules in the environment, and a wide range of other complex sample types.PMID:37260127 | DOI:10.1021/acs.analchem.2c04632

Analyst. 2023 Jun 1. doi: 10.1039/d3an00408b. Online ahead of print.ABSTRACTBacterial-fungal interactions (BFIs) can shape the structure of microbial communities, but the small molecules mediating these BFIs are often understudied. We explored various optimization steps for our microbial culture and chemical extraction protocols for bacterial-fungal co-cultures, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed that metabolomic profiles are mainly comprised of fungi derived features, indicating that fungi are the key contributors to small molecules in BFIs. LC-inductively coupled plasma MS (LC-ICP-MS) and MS/MS based dereplication using database searching revealed the presence of several known fungal specialized metabolites and structurally related analogues in these extracts, including siderophores such as desferrichrome, desferricoprogen, and palmitoylcoprogen. Among these analogues, a novel putative coprogen analogue possessing a terminal carboxylic acid motif was identified from Scopulariopsis sp. JB370, a common cheese rind fungus, and its structure was elucidated via MS/MS fragmentation. Based on these findings, filamentous fungal species appear to be capable of producing multiple siderophores with potentially different biological roles (i.e. various affinities for different forms of iron). These findings highlight that fungal species are important contributors to microbiomes via their production of abundant specialized metabolites and that elucidating their role in complex communities should continue to be a priority.PMID:37259951 | DOI:10.1039/d3an00408b

Mol Syst Biol. 2023 Jun 1:e11267. doi: 10.15252/msb.202211267. Online ahead of print.ABSTRACTWhile cellular metabolism impacts the DNA damage response, a systematic understanding of the metabolic requirements that are crucial for DNA damage repair has yet to be achieved. Here, we investigate the metabolic enzymes and processes that are essential for the resolution of DNA damage. By integrating functional genomics with chromatin proteomics and metabolomics, we provide a detailed description of the interplay between cellular metabolism and the DNA damage response. Further analysis identified that Peroxiredoxin 1, PRDX1, contributes to the DNA damage repair. During the DNA damage response, PRDX1 translocates to the nucleus where it reduces DNA damage-induced nuclear reactive oxygen species. Moreover, PRDX1 loss lowers aspartate availability, which is required for the DNA damage-induced upregulation of de novo nucleotide synthesis. In the absence of PRDX1, cells accumulate replication stress and DNA damage, leading to proliferation defects that are exacerbated in the presence of etoposide, thus revealing a role for PRDX1 as a DNA damage surveillance factor.PMID:37259925 | DOI:10.15252/msb.202211267

J Clin Invest. 2023 Jun 1;133(11):e170195. doi: 10.1172/JCI170195.ABSTRACTFumarate hydratase-deficient (FH-deficient) renal cell carcinoma (RCC) represents a particularly aggressive form of kidney cancer. FH-deficient RCC arises in the setting of germline, or solely somatic, mutations in the FH gene, a two-hit tumor suppressor gene. Early detection can be curative, but there are no biomarkers, and in the sporadic setting, establishing a diagnosis of FH-deficient RCC is challenging. In this issue of the JCI, Zheng, Zhu, and co-authors report untargeted plasma metabolomic analyses to identify putative biomarkers. They discovered two plasma metabolites directly linked to fumarate overproduction by tumor cells, succinyl-adenosine and succinic-cysteine, which correlate with tumor burden. The identification of circulating biomarkers of FH-deficient RCC may aid in the diagnosis of FH-deficient RCC and provide a means for longitudinal follow-up.PMID:37259915 | DOI:10.1172/JCI170195

Se Pu. 2023 Jun 8;41(6):520-526. doi: 10.3724/SP.J.1123.2022.10003.ABSTRACTGas chromatography-mass spectrometry (GC-MS) detectors are widely used detection instruments owing to their distinct advantages over other analytical techniques, including lower sample consumption, higher sensitivity, faster analysis speed, and simultaneous separation and analysis. Metabolomics is an important component of system physiology that concerns systematic studies of the metabolite spectrum in one or more biological systems, such as cells, tissues, organs, body fluids, and organisms. Unfortunately, conventional GC-MS detectors also feature low scan rates, high ion loss rates, and a narrow concentration detection range, which limit their applications in the field of metabolomics. Therefore, establishing a GC-MS-based metabolomic analysis method with wide coverage is of great importance. In this research, a widely-targeted metabolomics method based on GC-MS is proposed. This method combines the universality of untargeted metabolomics with the accuracy of targeted metabolomics to realize the qualitative and semi-quantitative detection of numerous metabolites. It does not require a self-built database and exhibits high sensitivity, good repeatability, and strong support for a wide range of metabolic substances. The proposed method was used to establish the relationship between the retention time of straight-chain fatty acid methyl esters (FAMEs) and their retention index (RI) in the FiehnLib database based on the metabolite information stored in this database. We obtained a linear relationship that could be described by the equation y=40878x-47530, r2=0.9999. We then calculated the retention times of metabolites in the FiehnLib database under the experimental conditions based on their RI. In this way, the effects of significant variations in peak retention times owing to differences in the chromatographic column, temperature, carrier gas flow rate, and so on can be avoided. The retention time of a substance fluctuates within a certain threshold because of variations in instrument performance, matrix interference, and other factors. As such, the retention time threshold of the substance must be determined. In this paper, the retention time threshold was set to 0.15 min to avoid instrument fluctuations. The optimal scan interval was optimized to 0.20 s (possible values=0.10, 0.15, 0.20, 0.25, and 0.30 s) because longer sampling periods can lead to spectral data loss and reductions in the resolution of adjacent chromatographic peaks, whereas shorter sampling periods can result in deterioration of the signal-to-noise ratio of the collected signals. The metabolite quantification ions were optimized to avoid the interference of quantification ion peak accumulation in the case of similar peak times, and a selected ion monitoring (SIM) method table was constructed for 611 metabolites, covering 65% of the metabolic pathways in the KEGG (Kyoto Encyclopedia of Genes and Genomes). The developed method covered 39 pathways, including glycolysis, the tricarboxylic acid cycle, purine metabolism, pyrimidine metabolism, amino acid metabolism, and biosynthesis. Compared with the full-scan untargeted GC-MS method, the widely-targeted GC-MS method demonstrated a 20%-30% increase in the number of metabolites detected, as well as a 15%-20% increase in signal-to-noise ratio. The results of stability tests showed that 84% of the intraday relative standard deviations (RSDs) of metabolite retention times were less than 2% and 91% of that were less than 3%; moreover, 54% of the interday RSDs of metabolite retention times were less than 2% and 76% of that were less than 3%. The detection and analysis results of common biological samples confirmed that the proposed method greatly improved the quantity and signal-to-noise ratio of the detected metabolites and is applicable to substances that are thermally stable, volatile, or volatile after derivation and have relative molecular masses lower than 600. Thus, the widely-targeted GC-MS method can expand the application scope of GC-MS in metabolomics.PMID:37259877 | DOI:10.3724/SP.J.1123.2022.10003

Pharmaceuticals (Basel). 2023 Feb 6;16(2):245. doi: 10.3390/ph16020245.ABSTRACTSpiked centaury (Centaurium spicatum) is a well-known medicinal plant from the Mediterranean region with various bioactivities, but there are no studies addressing the use of different solvent systems to improve its pharmacological potential. Nine extraction procedures were adapted to study the effects of solvent composition on the content of bioactive compounds in C. spicatum extracts and on corresponding bioactivities. Targeted metabolomics was performed to obtain information on the chemical composition of extracts. Ethanol-water-based extraction procedures were the most efficient in isolating polyphenols, while less polar butanol extract contained the highest amount of iridoids. Antioxidant potential analysis revealed stronger activity in extracts with higher polyphenol content. Bacillus cereus and Staphylococus aureus were designated as the most sensitive bacterial strains to the activity of extracts, while among the micromycetes tested, Penicillium funiculosum was the most susceptible strain. Butanol extract showed antivirulence potential on Candida albicans morphological transition from yeast to hyphal form, and selected extracts were effective against biofilm formation in two Candida species. All the extracts tested in this study showed no cytotoxic activity to immortalize human skin keratinocyte cell line (HaCaT), whereas extracts obtained by ethanol-water extraction stand out for their potent wound healing effects. Moreover, the influence of the extraction solvent system on various bioactivities of C. spicatum is reported herein for the first time. Overall, the results presented in this study promote the use of C. spicatum as a source of natural products with potential antioxidant, wound healing, and antimicrobial applications that are potentially safe for human use.PMID:37259391 | DOI:10.3390/ph16020245

J Am Soc Nephrol. 2023 Jun 1;34(6):1124-1125. doi: 10.1681/ASN.0000000000000138. Epub 2023 Apr 24.NO ABSTRACTPMID:37259199 | DOI:10.1681/ASN.0000000000000138

Arq Bras Cir Dig. 2023 May 26;36:e1734. doi: 10.1590/0102-672020230016e1734. eCollection 2023.ABSTRACTBACKGROUND: Fat, muscle, and bone are endocrine organs capable of affecting the metabolic profile and cardiovascular risk. Relating these components is important to the establishment of early intervention strategies for overweight patients.AIMS: This study aimed to evaluate the influence of body mass components on the metabolic profile and cardiovascular risk in the preoperative period of bariatric surgery.METHODS: A cross-sectional study was conducted with patients admitted for bariatric surgery at a university hospital in the city of Recife, Brazil, between 2018 and 2019. Body composition was determined using dual-energy x-ray absorptiometry. Cardiovascular risk was assessed using the Framingham risk score. Data were collected on anthropometric, clinical, and lifestyle characteristics. The lipid profile (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides), blood glucose, and vitamin D were determined using the standard methods of the hospital laboratory.RESULTS: A total of 60 patients were analyzed, 86.7% of whom had comorbidities, 33.3% had moderate/high cardiovascular risk, and 71.4% had vitamin D insufficiency/deficiency. Lower lean body mass (adjusted PR 3.24; 95%CI 1.19-5.77) was independently associated with the severity of obesity. The body mass index and waist circumference were negatively correlated with lean body mass (r=-0.52; p<0.01)/r=-0.36; p<0.01). Lean body mass was negatively correlated with fat mass (r=-0.26; p<0.05), trunk fat (r=-0.29; p<0.05), fasting glucose (r=-0.26; p<0.05), and bone mineral density (r=-0.26; p<0.05). A total of 84.2% of individuals with less trunk fat tended to have low cardiovascular risk (p=0.05). However, physical inactivity (adjusted PR 2.14; 95%CI 1.19-5.54) and the risk of alcohol dependence (adjusted PR 2.41; 95%CI 1.76-4.15) were the only variables independently associated with cardiovascular risk.CONCLUSION: Obese patients in the preoperative period of bariatric surgery with less trunk fat tended to have low cardiovascular risk. However, the other components of body mass were also not associated with cardiovascular risk.PMID:37255103 | DOI:10.1590/0102-672020230016e1734

Food Res Int. 2023 Jul;169:112841. doi: 10.1016/j.foodres.2023.112841. Epub 2023 Apr 17.ABSTRACTThe purpose of this study was to evaluate the effects of pasteurization and spray drying on goat milk lipids by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) and multiple variable statistics. A total of 1061 lipids assigned to 29 subclasses in raw and thermal-treated groups were identified. One hundred and 85 different lipids (DLs) (VIP ≥ 1 and |Log2FC| ≥ 1.0) were selected from pairwise comparisons of goat milk by different treatments. Glycerophospholipids were the most affected subclasses by thermal processes, especially by spray drying. Five potential lipid markers [(DG (16:1_18:0), TG (18:1_22:1_18:2), Cer (t17:2/31:0), LPC (0:0/20:0), and LPS (20:0/0:0] were used to distinguish different treated goat milk. Moreover, glycerophospholipid metabolism was the primary pathway of DLs. These results would provide more details of lipid profiles in thermally treated (pasteurization and spray drying) goat milk.PMID:37254416 | DOI:10.1016/j.foodres.2023.112841

Food Res Int. 2023 Jul;169:112740. doi: 10.1016/j.foodres.2023.112740. Epub 2023 Mar 21.ABSTRACTThe geographical traceability of food products is seen as a distinctive feature of the future of food which is increasingly becoming a concern for consumers. In this research, differences in the lipid composition of Coix seed samples from four major Chinese origins were investigated using non-targeted lipidomics. By multivariate statistical analysis, unsupervised PCA and OPLS-DA based differentiation between the four origins of Coix seed samples could be achieved. The OPLS-DA VIP > 1 screened 72 lipids out of 1211 lipids as potential markers to distinguish Coix seeds from different origins. In addition, the potential markers (SPH(d16:0), Cer(d18:2/20:0 + O) and PC(8:0e/8:0) were combined with statistical analysis algorithms to construct a discriminant function for rapid differentiation of Coix seed samples from different origins and a specific function for different origins with 100% discrimination accuracy. In general, a rapid and accurate method combining multivariate chemometrics and algorithms was developed based on untargeted lipidomics to determine the geographical origin of Coix seed samples, which can also be applied to other agricultural products.PMID:37254373 | DOI:10.1016/j.foodres.2023.112740

Food Res Int. 2023 Jul;169:112916. doi: 10.1016/j.foodres.2023.112916. Epub 2023 Apr 29.ABSTRACTThis investigation aims to elucidate the roles of lipids on the volatilome evolution of postmortem lamb and its possible modulated mechanism behind. Firstly, the physicochemical properties were evaluated as coordinating role of flavor quality, and results suggested that chilled storage improved tenderness of muscle tissue and induced color variation of lamb. According to multivariate results, the pattern shifts of volatile profile of chilled lamb could be differentiated successfully. Besides, the potential differential aroma-active compounds were identified, including up-regulated heptanol, 1-octen-3-ol, 6-methyl-2-heptanone, 3-heptanone, 2-pentyl furan and octanol in early stage of storage (days 0-3) and down-regulated hexanal, pentanal, hexanol, octanol, 6-methy-2-heptanone, heptanol, 1-octen-3-ol and benzaldehyde in later stage of storage (days 3-7). Then, discriminant analysis recognized the differential lipid species corresponding to different stages of lamb flavor development, involving phospholipids, sphingolipids, glycerolipids and fatty acyls. Herein, the degradation of acyl carnitine and diglyceride may be an important pathway that contributed to volatilome evolution of postmortem lamb in the early stage of storage. These results demonstrated a potential relationship between headspace volatilome and lipidome evolutions, providing a comprehensive understanding for development of lipid-derived volatile compounds of chilled lamb and useful for lamb characteristic flavor quality evaluation and control in future.PMID:37254350 | DOI:10.1016/j.foodres.2023.112916

BMC Genomics. 2023 May 31;24(1):293. doi: 10.1186/s12864-023-09382-6.ABSTRACTAs one of the important traits in pig production, meat quality has important research significance and value. Intramuscular fat (IMF) content is one of the most important factors affecting pork quality. Many experimental studies have shown that IMF content is closely related to the flavor, tenderness, and juiciness of pork. Therefore, it is of great significance to study the mechanism of porcine IMF deposition. Previous research indicated that miR-149-5p promoted the proliferation of porcine intramuscular (IM) preadipocytes and decreased their ability to differentiate, albeit the exact mechanism of action is unknown. In vitro, foreign pigs showed increased miR-149-5p expression and reduced fat deposition when compared to Queshan Black pigs. This study conducted metabolomics and transcriptomics analyses of porcine IM preadipocytes overexpressing miR-149-5p to verify their effects on lipid formation. According to metabolomics analysis, the overexpression of miR-149-5p has significantly altered the lipid, organic acid, and organic oxygen metabolites of porcine IM preadipocytes. Specially speaking, it has changed 115 metabolites, including 105 up-regulated and 10 down-regulated ones, as well as the composition of lipid, organic acid, and organic oxygen metabolism-related metabolites. RNA-seq analysis showed that overexpression of miR-149-5p significantly altered 857 genes, of which 442 were up-regulated, and 415 were down-regulated, with enrichment to MAPK, IL-17, PI3K-Akt, and ErbB signaling pathways. We found that overexpression of miR-149-5p inhibited adipogenic differentiation by changing cAMP signaling pathway in porcine IM preadipocytes. In addition, the overexpression of miR-149-5p may affect the transport of Cu2+ by targeting ATP7A and inhibiting adipogenic differentiation. These findings elucidate the regulatory function of miR-149-5p in porcine IM preadipocytes, which may be a key target for controlling pork quality.PMID:37259030 | DOI:10.1186/s12864-023-09382-6

Geroscience. 2023 May 31. doi: 10.1007/s11357-023-00827-0. Online ahead of print.ABSTRACTThe degenerative processes that occur during aging increase the risk of disease and impaired health. Meanwhile, interventions that target aging to promote healthy longevity are gaining interest, both academically and in the public. While nutritional and physical interventions exist, efficacy is often difficult to determine. It is therefore imperative that an aging score measuring the biological aging process is available to the wider public. However, simple, interpret, and accessible biological aging scores are lacking. Here, we developed PhysiAge, a physiological aging score based on five accessible parameters that have influence on or reflect the aging process: (1) average daily step count, (2) blood glucose, (3) systolic blood pressure, (4) sex, and (5) age. Here, we found that compared to calendar age alone, PhysiAge better predicts mortality, as well as established muscle aging markers such as decrease in NAD+ levels, increase in oxidative stress, and decline in physical functioning. In order to demonstrate the usefulness of PhysiAge in identifying relevant factors associated with decelerated aging, we calculated PhysiAges for a cohort of aged individuals and obtained mass spectrometry-based blood plasma metabolomic profiles for each individual. Here, we identified a metabolic signature of decelerated aging, which included components of the TCA cycle, including malate, citrate, and isocitrate. Higher abundance of these metabolites was associated with decelerated aging, in line with supplementation studies in model organisms. PhysiAge represents an accessible way for people to track and intervene in their aging trajectories, and identifies a metabolic signature of decelerated aging in human blood plasma, which can be further studied for its causal involvement in human aging.PMID:37259015 | DOI:10.1007/s11357-023-00827-0

Methods Mol Biol. 2023;2675:195-204. doi: 10.1007/978-1-0716-3247-5_15.ABSTRACTNuclear magnetic resonance (NMR) spectroscopy enables the detection and the quantification of a large range of molecules, including low-molecular-weight metabolites and lipids. NMR spectroscopy is a powerful approach when applied to the high-throughput analysis of plasma or serum samples allowing, in addition, the detection of total proteins, lipoproteins, and signals arising from the glycosylation of circulating acute-phase proteins. Here, we describe the usage of NMR spectroscopy for profiling the plasma or serum of patients with prostate cancer.PMID:37258765 | DOI:10.1007/978-1-0716-3247-5_15

Methods Mol Biol. 2023;2675:167-180. doi: 10.1007/978-1-0716-3247-5_13.ABSTRACTHuman metabolic liver disease is dramatically increasing globally and presents an urgent clinical unmet need. Rodent models of non-alcoholic fatty liver disease (NAFLD) are available, but they fail to fully recreate the metabolic and cellular features of human disease. Thus, it is imperative to understand the metabolic interplay in human cells in the context of disease. We have applied nuclear magnetic resonance (NMR) spectroscopy approaches to enable the detection of numerous metabolites in human cells and within intact tissue in a single measurement. In this chapter, we describe the challenges of using isolated human hepatocytes vs perfused human liver tissue for metabolic tracer experiments and how experimental parameters can be refined to interrogate signals from intact tissue and cells.PMID:37258763 | DOI:10.1007/978-1-0716-3247-5_13

Sci Rep. 2023 May 31;13(1):8867. doi: 10.1038/s41598-023-35652-0.ABSTRACTNutrient availability in eggs can affect early metabolic orientation in birds. In chickens divergently selected on the Pectoralis major ultimate pH, a proxy for muscle glycogen stores, characterization of the yolk and amniotic fluid revealed a different nutritional environment. The present study aimed to assess indicators of embryo metabolism in pHu lines (pHu+ and pHu-) using allantoic fluids (compartment storing nitrogenous waste products and metabolites), collected at days 10, 14 and 17 of embryogenesis and characterized by 1H-NMR spectroscopy. Analysis of metabolic profiles revealed a significant stage effect, with an enrichment in metabolites at the end of incubation, and an increase in interindividual variability during development. OPLS-DA analysis discriminated the two lines. The allantoic fluid of pHu- was richer in carbohydrates, intermediates of purine metabolism and derivatives of tryptophan-histidine metabolism, while formate, branched-chain amino acids, Krebs cycle intermediates and metabolites from different catabolic pathways were more abundant in pHu+. In conclusion, the characterization of the main nutrient sources for embryos and now allantoic fluids provided an overview of the in ovo nutritional environment of pHu lines. Moreover, this study revealed the establishment, as early as day 10 of embryo development, of specific metabolic signatures in the allantoic fluid of pHu+ and pHu- lines.PMID:37258592 | DOI:10.1038/s41598-023-35652-0

NPJ Biofilms Microbiomes. 2023 May 31;9(1):29. doi: 10.1038/s41522-023-00399-z.ABSTRACTNon-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease, had no approved pharmacological agents yet. Obeticholic acid (OCA), a novel bile acid derivative, was demonstrated to ameliorate NAFLD-related manifestations. Regarding the role of gut-liver axis in liver disease development, this study aimed to explore the potential role of gut microbiota in the treatment of OCA in NAFLD mice induced by the high-fat diet (HFD). Antibiotic-induced microbiome depletion (AIMD) and fecal microbiota transplantation (FMT) confirmed the critical role of gut microbiota in OCA treatment for NAFLD by effectively alleviating histopathological lesions and restoring liver function impaired by HFD. Metagenomic analysis indicated that OCA intervention in HFD mice remarkably increased the abundance of Akkermansia muciniphila, Bifidobacterium spp., Bacteroides spp., Alistipes spp., Lactobacillus spp., Streptococcus thermophilus, and Parasutterella excrementihominis. Targeted metabolomics analysis indicated that OCA could modulate host bile acids pool by reducing levels of serum hydrophobic cholic acid (CA) and chenodeoxycholic acid (CDCA), and increasing levels of serum-conjugated bile acids, such as taurodeoxycholic acid (TDCA) and tauroursodesoxycholic acid (TUDCA) in the HFD-fed mice. Strong correlations were observed between differentially abundant microbes and the shifted bile acids. Furthermore, bacteria enriched by OCA intervention exhibited much greater potential in encoding 7alpha-hydroxysteroid dehydrogenase (7α-HSDs) producing secondary bile acids rather than bile salt hydrolases (BSHs) mainly responsible for primary bile acid deconjugation. In conclusion, this study demonstrated that OCA intervention altered gut microbiota composition with specially enriched gut microbes modulating host bile acids, thus effectively alleviating NAFLD in the mice.PMID:37258543 | DOI:10.1038/s41522-023-00399-z