PubMed

Toxicology. 2023 May 18:153550. doi: 10.1016/j.tox.2023.153550. Online ahead of print.ABSTRACTOrgan-on-chip technology is a promising in vitro approach recapitulating human physiology for the study of responses to drug exposure. Organ-on-chip cell cultures have paved new grounds for testing and understanding metabolic dose-responses when evaluating pharmaceutical and environmental toxicity. Here, we present a metabolomic investigation of a coculture of liver sinusoidal endothelial cells (LSECs, SK-HEP-1) with hepatocytes (HepG2/C3a) using advanced organ-on-chip technology. To reproduce the physiology of the sinusoidal barrier, LSECs were separated from hepatocytes by a membrane (culture insert integrated organ-on-chip platform). The tissues were exposed to acetaminophen (APAP), an analgesic drug widely used as a xenobiotic model in liver and HepG2/C3a studies. The differences between the SK-HEP-1, HepG2/C3a monocultures and SK-HEP-1/HepG2/C3a cocultures, treated or not with APAP, were identified from metabolomic profiles using supervised multivariate analysis. The pathway enrichment coupled with metabolite analysis of the corresponding metabolic fingerprints contributed to extracting the specificity of each type of culture and condition. In addition, we analysed the responses to APAP treatment by mapping the signatures with significant modulation of the biological processes of the SK-HEP-1 APAP, HepG2/C3a APAP and SK-HEP-1/HepG2/C3a APAP conditions. Furthermore, our model shows how the presence of the LSECs barrier and APAP first pass can modify the metabolism of HepG2/C3a. Altogether, this study demonstrates the potential of a "metabolomic-on-chip" strategy for pharmaco-metabolomic applications predicting individual response to drugs.PMID:37209942 | DOI:10.1016/j.tox.2023.153550

Metab Eng. 2023 May 18:S1096-7176(23)00068-X. doi: 10.1016/j.ymben.2023.05.002. Online ahead of print.ABSTRACTKinetic models are key to understanding and predicting the dynamic behaviour of metabolic systems. Traditional models require kinetic parameters which are not always available and are often estimated in vitro. Ensemble models overcome this challenge by sampling thermodynamically feasible models around a measured reference point. However, it is unclear if the convenient distributions used to generate the ensemble produce a natural distribution of model parameters and hence if the model predictions are reasonable. In this paper, we produced a detailed kinetic model for the central carbon metabolism of Escherichia coli. The model consists of 82 reactions (including 13 reactions with allosteric regulation) and 79 metabolites. To sample the model, we used metabolomic and fluxomic data from a single steady-state time point for E.coli K-12 MG1655 growing on glucose minimal M9 medium (average sampling time for 1000 models: 11.21 ± 0.14 min). Afterwards, in order to examine whether our sampled models are biologically sound, we calculated the Km, Vmax and kcat for the reactions and compared them to previously published values. Finally, we used metabolic control analysis to identify enzymes with high control over the fluxes in the central carbon metabolism. Our analyses demonstrate that our platform samples thermodynamically feasible kinetic models, which are in agreement with previously published experimental results and can be used to investigate metabolic control patterns within cells. This renders it a valuable tool for the study of cellular metabolism and the design of metabolic pathways.PMID:37209863 | DOI:10.1016/j.ymben.2023.05.002

Sci Total Environ. 2023 May 18:164258. doi: 10.1016/j.scitotenv.2023.164258. Online ahead of print.ABSTRACTCoral bleaching and coral reef degradation have been severely increased due to anthropogenic impacts, especially global warming. Studies have indicated the key role of host-microbiome symbiotic relationships for the coral holobiont health and development, although not all of the mechanisms of interaction have been fully explored. Here, we explore bacterial and metabolic shifts within coral holobionts under thermal stress, and its correlation with bleaching. Our results showed obvious signs of coral bleaching after 13 days of heating treatment, and a more-complex co-occurrence network was observed in the coral-associated bacterial community of the heating group. The bacterial community and metabolites changed significantly under thermal stress, and genera Flavobacterium, Shewanella and Psychrobacter increased from <0.1 % to 43.58 %, 6.95 % and 6.35 %, respectively. Bacteria potentially associated with stress tolerance, biofilm formation and mobile elements decreased from 80.93 %, 62.15 % and 49.27 % to 56.28 %, 28.41 % and 18.76 %, respectively. The differentially expressed metabolites of corals after heating treatment, such as Cer(d18:0/17:0), 1-Methyladenosine, Trp-P-1 and Marasmal, were associated with cell cycle regulation and antioxidant properties. Our results can contribute to our current understanding on the correlations between coral-symbiotic bacteria, metabolites and the coral physiological response to thermal stress. These new insights into the metabolomics of heat-stressed coral holobionts may expand our knowledge on the mechanisms underlying bleaching.PMID:37209734 | DOI:10.1016/j.scitotenv.2023.164258

Poult Sci. 2023 Apr 28;102(7):102762. doi: 10.1016/j.psj.2023.102762. Online ahead of print.ABSTRACTIncreasing evidence indicates that the gut microbiome plays an important role in host aging and sexual maturity. However, the gut microbial taxa associated with sexual maturity in quails are unknown. This study used shotgun metagenomic sequencing to identify bacterial taxa associated with sexual maturity in d 20 and d 70 quails. We found that 17 bacterial species and 67 metagenome-assembled genomes (e.g., Bacteroides spp. and Enterococcus spp.) significantly differed between the d 20 and d 70 groups, including 5 bacterial species (e.g., Enterococcus faecalis) enriched in the d 20 group and 12 bacterial species (e.g., Christensenella massiliensis, Clostridium sp. CAG:217, and Bacteroides neonati) which had high abundances in the d 70 group. The bacterial species enriched in d 20 or d 70 were key biomarkers distinguishing sexual maturity and significantly correlated with the shifts in the functional capacities of the gut microbiome. Untargeted serum metabolome analysis revealed that 5 metabolites (e.g., nicotinamide riboside) were enriched in the d 20 group, and 6 metabolites (e.g., D-ribose, stevioside, and barbituric acid) were enriched in the d 70 group. Furthermore, metabolites with high abundances in the d 20 group were significantly enriched for the KEGG pathways of arginine biosynthesis, nicotinate and nicotinamide metabolism, and lysine degradation. However, glutathione metabolism and valine, leucine and isoleucine biosynthesis were enriched in high-abundance metabolites from the d 70 group. These results provide important insights into the effects of gut microbiome and host metabolism on quail sexual maturity.PMID:37209654 | DOI:10.1016/j.psj.2023.102762

J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Mar 15;1224:123665. doi: 10.1016/j.jchromb.2023.123665. Online ahead of print.ABSTRACTXixin-Ganjiang Herb Pair (XGHP), a classic combination treatment to warm the lungs and dissolve phlegm, is widely used in the treatment of various pulmonary diseases. Chronic obstructive pulmonary disease (COPD) refers to a group of chronic obstructive airway diseases that can seriously harm human health. However, the effective components, targets, and pathways that underlie XGHP in the treatment of COPD remain unclear. Therefore, this study initially identified the effective components of XGHP through the use of UPLC-MS/MS and pharmacologic methods of traditional Chinese medicine. Secondly, transcriptomic analysis of the lung tissues of rats revealed the pharmacodynamic transcripts of each group, and metabolomics analysis revealed the differential metabolites associated with XGHP treatment. Finally, molecular docking of effective components with transcriptome genes was performed and western blotting was performed in order to determine the expression of related proteins in rat lung tissue. Overall, 30 effective components of XGHP were identified, including L-asarinin, 6-gingerol, sesamin, kaempferol, and quercetin. Transcriptomic studies demonstrated that expression of 386 genes recovered after XGHP treatment, and that they were mainly enriched in the oxidative phosphorylation and AMPK signaling pathways. According to the metabolomics studies, expression of eight metabolites differed between the COPD and the XGHP groups. These metabolites were mainly involved the biosynthesis of unsaturated fatty acids. Finally, the transcriptomic and metabolomics data were integrated. FASN and SCD in AMPK signaling pathway were directly linked to certain metabolites, including linoleic acid, palmitic acid, and oleic acid. These results indicate that XGHP can inhibit pAMPK expression and negatively regulate FASN and SCD expression during treatment of COPD in order to enhance the biosynthesis of unsaturated fatty acids and maintain energy homeostasis.PMID:37209557 | DOI:10.1016/j.jchromb.2023.123665

Food Chem. 2023 May 5;423:136273. doi: 10.1016/j.foodchem.2023.136273. Online ahead of print.ABSTRACTCarrots produced in different agricultural regions with organic or conventional mode were analyzed by untargeted UHPLC-HRMS using reversed-phase and HILIC modes. Data were first treated separately, and further combined to possibly improve results. An in-house data processing workflow was applied to identify relevant features after peak detection. Based on these features, discrimination models were built using chemometrics. A tentative annotation of chemical markers was performed using online databases and UHPLC-HRMS/MS analyses. An independent set of samples was analyzed to assess the discrimination potential of these markers. Carrots produced in the New Aquitaine region could be successfully discriminated from carrots originating from the Normandy region by an OLPS-DA model. Arginine and 6-methoxymellein could be identified as potential markers with the C18-silica column. Additional markers (N-acetylputrescine, l-carnitine) could be identified thanks to the polar column. Discrimination based on production mode was more challenging: some trend was observed but model metrics remained unsatisfactory.PMID:37209545 | DOI:10.1016/j.foodchem.2023.136273

J Pharm Biomed Anal. 2023 May 18;233:115464. doi: 10.1016/j.jpba.2023.115464. Online ahead of print.ABSTRACTHypertension is one of the most challenging public health problems worldwide. Previous studies suggested that the Uncaria rhynchophylla Scrophularia Formula (URSF), a medical institution preparation of the affiliated Hospital of Shandong University of Traditional Chinese Medicine, is effective for essential hypertension. However, the efficacy of URSF for hypertension remains unclear. We aimed to clarify the anti-hypertensive mechanism of the URSF. The material basis of URSF was identified by the LC-MS. We also evaluated the antihypertensive efficacy of URSF on SHR rats by body weight, blood pressure and biochemical indicators. The LC-MS spectrometry-based serum non-targeted metabolomics was used to seek potential biomarkers and relevant pathways for URSF in the treatment of SHR rats. 56 biomarkers were metabolically disturbed in SHR rats in the model group compared with the control group. After URSF intervention, 13 biomarkers showed a recovery in the optimal method compared with the other three groups. We identified 3 metabolic pathways in which URSF is involved: the arachidonic acid metabolism pathway, the niacin and nicotinamide metabolism pathway, and the purine metabolism pathway. These discoveries offer a basis for the study of URSF for the treatment of hypertension.PMID:37209496 | DOI:10.1016/j.jpba.2023.115464

J Sci Food Agric. 2023 May 20. doi: 10.1002/jsfa.12716. Online ahead of print.ABSTRACTBACKGROUND: Among type 2 diabetes (T2D) patients, the incidence rate of liver metabolic disorders is much higher than that in healthy subjects. It was observed in our previous research that diabetic symptoms were improved by Lactobacillus plantarum SHY130 (LPSHY130) isolated from yak yogurt in a murine model of type 2 diabetes (T2D). This study sought to investigate the LPSHY130-mediated hepatic metabolic regulation in a murine model of T2D.RESULTS: Treatment with LPSHY130 improved liver function and pathological damage in diabetic mice. Untargeted metabolome analysis revealed the T2D-induced changes in 11 metabolites were regulated after LPSHY130 treatment, mainly involving purine metabolism, amino acid metabolism, choline metabolism, and pantothenate and CoA biosynthesis pathways. In addition, correlation analysis indicated that hepatic metabolic changes can be adjusted by the intestinal microbiota.CONCLUSION: Overall, this study suggests that treatment with LPSHY130 relieves liver injury and regulates liver metabolism in a murine model of T2D, thus providing a theoretical basis for the use of probiotics as dietary supplements to regulate hepatic metabolic disorders associated with T2D. This article is protected by copyright. All rights reserved.PMID:37209399 | DOI:10.1002/jsfa.12716

J Clin Immunol. 2023 May 20. doi: 10.1007/s10875-023-01512-9. Online ahead of print.ABSTRACTAutoantibodies (auto-Abs) neutralizing type I interferons (IFNs) are found in the blood of at least 15% of unvaccinated patients with life-threatening COVID-19 pneumonia. We report here the presence of auto-Abs neutralizing type I IFNs in the bronchoalveolar lavage (BAL) of 54 of the 415 unvaccinated patients (13%) with life-threatening COVID-19 pneumonia tested. The 54 individuals with neutralizing auto-Abs in the BAL included 45 (11%) with auto-Abs against IFN-α2, 37 (9%) with auto-Abs against IFN-ω, 54 (13%) with auto-Abs against IFN-α2 and/or ω, and five (1%) with auto-Abs against IFN-β, including three (0.7%) with auto-Abs neutralizing IFN-α2, IFN-ω, and IFN-β, and two (0.5%) with auto-Abs neutralizing IFN-α2 and IFN-β. Auto-Abs against IFN-α2 also neutralize the other 12 subtypes of IFN-α. Paired plasma samples were available for 95 patients. All seven patients with paired samples who had detectable auto-Abs in BAL also had detectable auto-Abs in plasma, and one patient had auto-Abs detectable only in blood. Auto-Abs neutralizing type I IFNs are, therefore, present in the alveolar space of at least 10% of patients with life-threatening COVID-19 pneumonia. These findings suggest that these auto-Abs impair type I IFN immunity in the lower respiratory tract, thereby contributing to hypoxemic COVID-19 pneumonia.PMID:37209324 | DOI:10.1007/s10875-023-01512-9

Braz J Microbiol. 2023 May 20. doi: 10.1007/s42770-023-01001-6. Online ahead of print.ABSTRACTBrucellosis is a zoonosis prevalent worldwide and very recurrent in less developed or developing regions. This zoonosis affects livestock, generating high financial losses to producers, in addition to transmitting diseases to humans through meat consumption or handling contaminated products and animals. In this study, five extraction methods for Brucella abortus intracellular metabolites, using different solvent compositions and cell membrane disruption procedures, were evaluated. Derivatized extracts were analyzed by GC-HRMS. Raw data were processed in XCMS Online and the results were evaluated through multivariate statistical analysis using the MetaboAnalyst platform. The identification of the extracted metabolites was performed by the Unknowns software using the NIST 17.L library. The extraction performance of each method was evaluated for thirteen representative metabolites, comprising four different chemical classes. Most of these compounds are reported in the cell membrane composition of Gram-negative bacteria. The method based on extraction with methanol/chloroform/water presented the best performance in the evaluation of the extracted compounds and in the statistical results. Therefore, this method was selected for extracting intracellular metabolites from cultures of Brucella abortus for untargeted metabolomics analysis.PMID:37209273 | DOI:10.1007/s42770-023-01001-6

Cell Rep. 2023 May 18;42(5):112530. doi: 10.1016/j.celrep.2023.112530. Online ahead of print.ABSTRACTNonalcoholic fatty liver disease (NAFLD) is a chronic metabolic disorder caused by overnutrition and can lead to nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). The transcription factor Forkhead box K1 (FOXK1) is implicated in regulation of lipid metabolism downstream of mechanistic target of rapamycin complex 1 (mTORC1), but its role in NAFLD-NASH pathogenesis is understudied. Here, we show that FOXK1 mediates nutrient-dependent suppression of lipid catabolism in the liver. Hepatocyte-specific deletion of Foxk1 in mice fed a NASH-inducing diet ameliorates not only hepatic steatosis but also associated inflammation, fibrosis, and tumorigenesis, resulting in improved survival. Genome-wide transcriptomic and chromatin immunoprecipitation analyses identify several lipid metabolism-related genes, including Ppara, as direct targets of FOXK1 in the liver. Our results suggest that FOXK1 plays a key role in the regulation of hepatic lipid metabolism and that its inhibition is a promising therapeutic strategy for NAFLD-NASH, as well as for HCC.PMID:37209098 | DOI:10.1016/j.celrep.2023.112530

Insect Mol Biol. 2023 May 20. doi: 10.1111/imb.12850. Online ahead of print.ABSTRACTThe white epidermis of silkworms is due to the accumulation of uric acid crystals. Abnormal silkworm uric acid metabolism decreases uric acid production, leading to a transparent or translucent phenotype. The oily silkworm op50 is a mutant strain with a highly transparent epidermis derived from the p50 strain. It shows more susceptibility to Bombyx mori nucleopolyhedrovirus (BmNPV) infection than the wild type; however, the underlying mechanism is unknown. This study analysed the changes in 34 metabolites in p50 and op50 at different times following BmNPV infection based on comparative metabolomics. The differential metabolites were mainly clustered in six metabolic pathways. Of these, the uric acid pathway was identified as critical for resistance in silkworms, as feeding with inosine significantly enhanced larval resistance compared to other metabolites and modulated other metabolic pathways. Additionally, the increased level of resistance to BmNPV in inosine-fed silkworms was associated with the regulation of apoptosis, which is mediated by the reactive oxygen species produced during uric acid synthesis. Furthermore, feeding the industrial strain Jingsong (JS) with inosine significantly increased the level of larval resistance to BmNPV, indicating its potential application in controlling the virus in sericulture. These results lay the foundation for clarifying the resistance mechanism of silkworms to BmNPV and provide new strategies and methods for the biological control of pests.PMID:37209025 | DOI:10.1111/imb.12850

J Cachexia Sarcopenia Muscle. 2023 May 20. doi: 10.1002/jcsm.13251. Online ahead of print.ABSTRACTBACKGROUND: Androgens are anabolic steroid hormones that exert their function by binding to the androgen receptor (AR). We have previously established that AR deficiency in limb muscles impairs sarcomere myofibrillar organization and decreases muscle strength in male mice. However, despite numerous studies performed in men and rodents, the signalling pathways controlled by androgens via their receptor in skeletal muscles remain poorly understood.METHODS: Male ARskm-/y (n = 7-12) and female ARskm-/- mice (n = 9), in which AR is selectively ablated in myofibres of musculoskeletal tissue, and male AR(i)skm-/y , in which AR is selectively ablated in post-mitotic skeletal muscle myofibres (n = 6), were generated. Longitudinal monitoring of body weight, blood glucose, insulin, lipids and lipoproteins was performed, alongside metabolomic analyses. Glucose metabolism was evaluated in C2C12 cells treated with 5α-dihydrotestosterone (DHT) and the anti-androgen flutamide (n = 6). Histological analyses on macroscopic and ultrastructural levels of longitudinal and transversal muscle sections were conducted. The transcriptome of gastrocnemius muscles from control and ARskm-/y mice was analysed at the age of 9 weeks (P < 0.05, 2138 differentially expressed genes) and validated by RT-qPCR analysis. The AR (4691 peaks with false discovery rate [FDR] < 0.1) and H3K4me2 (47 225 peaks with FDR < 0.05) cistromes in limb muscles were determined in 11-week-old wild-type mice.RESULTS: We show that disrupting the androgen/AR axis impairs in vivo glycolytic activity and fastens the development of type 2 diabetes in male, but not in female mice. In agreement, treatment with DHT increases glycolysis in C2C12 myotubes by 30%, whereas flutamide has an opposite effect. Fatty acids are less efficiently metabolized in skeletal muscles of ARskm-/y mice and accumulate in cytoplasm, despite increased transcript levels of genes encoding key enzymes of beta-oxidation and mitochondrial content. Impaired glucose and fatty acid metabolism in AR-deficient muscle fibres is associated with 30% increased lysine and branched-chain amino acid catabolism, decreased polyamine biosynthesis and disrupted glutamate transamination. This metabolic switch generates ammonia (2-fold increase) and oxidative stress (30% increased H2 O2 levels), which impacts mitochondrial functions and causes necrosis in <1% fibres. We unravel that AR directly activates the transcription of genes involved in glycolysis, oxidative metabolism and muscle contraction.CONCLUSIONS: Our study provides important insights into diseases caused by impaired AR function in musculoskeletal system and delivers a deeper understanding of skeletal muscle pathophysiological dynamics that is instrumental to develop effective treatment for muscle disorders.PMID:37208984 | DOI:10.1002/jcsm.13251

Biotechnol Biofuels Bioprod. 2023 May 19;16(1):84. doi: 10.1186/s13068-023-02338-8.ABSTRACTBACKGROUND: Diatoms have been viewed as ideal cell factories for production of some high-value bioactive metabolites, such as fucoxanthin, but their applications are restrained by limited biomass yield. Mixotrophy, by using both CO2 and organic carbon source, is believed effective to crack the bottleneck of biomass accumulation and achieve a sustainable bioproduct supply.RESULTS: Glycerol, among tested carbon sources, was proved as the sole that could significantly promote growth of Cylindrotheca sp. with illumination, a so-called growth pattern, mixotrophy. Biomass and fucoxanthin yields of Cylindrotheca sp., grown in medium with glycerol (2 g L-1), was increased by 52% and 29%, respectively, as compared to the autotrophic culture (control) without compromise in photosynthetic performance. As Cylindrotheca sp. was unable to use glycerol without light, a time-series transcriptomic analysis was carried out to elucidate the light regulation on glycerol utilization. Among the genes participating in glycerol utilization, GPDH1, TIM1 and GAPDH1, showed the highest dependence on light. Their expressions decreased dramatically when the alga was transferred from light into darkness. Despite the reduced glycerol uptake in the dark, expressions of genes associating with pyrimidine metabolism and DNA replication were upregulated when Cylindrotheca sp. was cultured mixotrophically. Comparative transcriptomic and metabolomic analyses revealed amino acids and aminoacyl-tRNA metabolisms were enhanced at different timepoints of diurnal cycles in mixotrophic Cylindrotheca sp., as compared to the control.CONCLUSIONS: Conclusively, this study not only provides an alternative for large-scale cultivation of Cylindrotheca, but also pinpoints the limiting enzymes subject to further metabolic manipulation. Most importantly, the novel insights in this study should aid to understand the mechanism of biomass promotion in mixotrophic Cylindrotheca sp.PMID:37208696 | DOI:10.1186/s13068-023-02338-8

BMC Genomics. 2023 May 19;24(1):272. doi: 10.1186/s12864-023-09361-x.ABSTRACTMacrophages are important effector cells in tumor progression and immune regulation. Previously, we demonstrated that the transcription suppressor homeobox containing 1(HMBOX1) exhibits immunosuppressive activity in LPS-induced acute liver injury by impeding macrophage infiltration and activation. We also observed a lower proliferation in HMBOX1-overexpressed RAW264.7 cells. However, the specific mechanism was unclear. Here, a work was performed to characterize HMBOX1 function related to cell proliferation from a metabolomics standpoint by comparing the metabolic profiles of HMBOX1-overexpressed RAW264.7 cells to those of the controls. Firstly, we assessed HMBOX1 anti-proliferation activity in RAW264.7 cells with CCK8 assay and clone formation. Then, we performed metabolomic analyses by ultra-liquid chromatography coupled with mass spectrometry to explore the potential mechanisms. Our results indicated that HMBOX1 inhibited the macrophage growth curve and clone formation ability. Metabolomic analyses showed significant changes in HMBOX1-overexpressed RAW264.7 metabolites. A total of 1312 metabolites were detected, and 185 differential metabolites were identified based on the criterion of OPLS-DA VIP > 1 and p value < 0.05. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the elevated HMBOX1 in RAW264.7 inhibited the pathways of amino acid and nucleotide metabolism. Glutamine concentrations decreased significantly in HMBOX1-overexpressed macrophages, and glutamine-related transporter SLC1A5 was also downregulated. Furthermore, SLC1A5 overexpression reversed HMBOX1 inhibition of macrophage proliferation. This study demonstrated the potential mechanism of the HMBOX1/SLC1A5 pathway in cell proliferation by regulating glutamine transportation. The results may help provide a new direction for therapeutic interventions in macrophage-related inflammatory diseases.PMID:37208615 | DOI:10.1186/s12864-023-09361-x

BMC Gastroenterol. 2023 May 19;23(1):161. doi: 10.1186/s12876-023-02803-6.ABSTRACTINTRODUCTION: Chronic erosive gastritis (CEG) is closely related to gastric cancer, which requires early diagnosis and intervention. The invasiveness and discomfort of electronic gastroscope have limited its application in the large-scale screening of CEG. Therefore, a simple and noninvasive screening method is needed in the clinic.OBJECTIVES: The aim of this study is to screen potential biomarkers that can identify diseases from the saliva samples of CEG patients using metabolomics.METHODS: Saliva samples from 64 CEG patients and 30 healthy volunteers were collected, and metabolomic analysis was performed using UHPLC-Q-TOF/MS in the positive and negative ion modes. Statistical analysis was performed using both univariate (Student's t-test) and multivariate (orthogonal partial least squares discriminant analysis) tests. Receiver operating characteristic (ROC) analysis was conducted to determine significant predictors in the saliva of CEG patients.RESULTS: By comparing the saliva samples from CEG patients and healthy volunteers, 45 differentially expressed metabolites were identified, of which 37 were up-regulated and 8 were down-regulated. These differential metabolites were related to amino acid, lipid, phenylalanine metabolism, protein digestion and absorption, and mTOR signaling pathway. In the ROC analysis, the AUC values of 7 metabolites were greater than 0.8, among which the AUC values of 1,2-dioleoyl-sn-glycoro-3-phosphodylcholine and 1-stearoyl-2-oleoyl-sn-glycoro-3-phospholine (SOPC) were greater than 0.9.CONCLUSIONS: In summary, a total of 45 metabolites were identified in the saliva of CEG patients. Among them, 1,2-dioleoyl-sn-glycoro-3-phosphorylcholine and 1-stearoyl-2-oleoyl-sn-glycoro-3-phosphorine (SOPC) might have potential clinical application value.PMID:37208605 | DOI:10.1186/s12876-023-02803-6

BMC Genomics. 2023 May 19;24(1):267. doi: 10.1186/s12864-023-09317-1.ABSTRACTBACKGROUND: Oriental river prawn Macrobrachium nipponense is an economically important aquaculture species in China, Japan, and Vietnam. In commercial prawn farming, feed cost constitutes about 50 to 65% of the actual variable cost. Improving feed conversion efficiency in prawn culture will not only increase economic benefit, but also save food and protect the environment. The common indicators used for feed conversion efficiency include feed conversion ratio (FCR), feed efficiency ratio (FER), and residual feed intake (RFI). Among these, RFI is much more suitable than FCR and FER during the genetic improvement of feed conversion efficiency for aquaculture species.RESULTS: In this study, the transcriptome and metabolome of hepatopancreas and muscle of M. nipponense from high RFI low RFI groups, which identified after culture for 75 days, were characterized using combined transcriptomic and metabolomic analysis. A total of 4540 differentially expressed genes (DEGs) in hepatopancreas, and 3894 DEGs in muscle were identified, respectively. The DEGs in hepatopancreas were mainly enriched in KEGG pathways including the metabolism of xenobiotics by cytochrome P450 (down-regulated), fat digestion and absorption (down-regulated) and aminoacyl-tRNA biosynthesis (up-regulated), etc. The DEGs in muscle were mainly enriched in KEGG pathways including the protein digestion and absorption (down-regulated), glycolysis/gluconeogenesis (down-regulated), and glutathione metabolism (up-regulated), etc. At the transcriptome level, the RFI of M. nipponense was mainly controlled in biological pathways such as the high immune expression and the reduction of nutrients absorption capacity. A total of 445 and 247 differently expressed metabolites (DEMs) were identified in the hepatopancreas and muscle, respectively. At the metabolome level, the RFI of M. nipponense was affected considerably by amino acid and lipid metabolism.CONCLUSIONS: M. nipponense from higher and lower RFI groups have various physiological and metabolic capability processes. The down-regulated genes, such as carboxypeptidase A1, 6-phosphofructokinase, long-chain-acyl-CoA dehydrogenase, et. al., in digestion and absorption of nutrients, and the up-regulated metabolites, such as aspirin, lysine, et. al., in response to immunity could be potential candidate factors contributed to RFI variation for M. nipponense. Overall, these results would provide new insights into the molecular mechanism of feed conversion efficiency and assist in selective breeding to improve feed conversion efficiency in M. nipponense.PMID:37208591 | DOI:10.1186/s12864-023-09317-1

Curr Obes Rep. 2023 May 19. doi: 10.1007/s13679-023-00503-6. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: The review aims to describe short-chain fatty acids (SCFAs) as metabolites of bacteria, their complex influence on whole-body metabolism, and alterations in the SCFA profile in obesity and after bariatric surgery (BS).RECENT FINDINGS: The fecal profile of SCFAs in obese patients differs from that of lean patients, as well as their gut microbiota composition. In obese patients, a lower diversity of bacteria is observed, as well as higher concentrations of SCFAs in stool samples. Obesity is now considered a global epidemic and bariatric surgery (BS) is an effective treatment for severe obesity. BS affects the structure and functioning of the digestive system, and also alters gut microbiota and the concentration of fecal SCFAs. Generally, after BS, SCFA levels are lower but levels of branched short-chain fatty acids (BSCFAs) are elevated, the effect of which is not fully understood. Moreover, changes in the profile of circulating SCFAs are little known and this is an area for further research. Obesity seems to be inherently associated with changes in the SCFA profile. It is necessary to better understand the impact of BS on microbiota and the metabolome in both feces and blood as only a small percentage of SCFAs are excreted. Further research may allow the development of a personalized therapeutic approach to the BS patient in terms of diet and prebiotic intervention.PMID:37208544 | DOI:10.1007/s13679-023-00503-6

Nat Commun. 2023 May 19;14(1):2876. doi: 10.1038/s41467-023-38403-x.ABSTRACTTumors are comprised of a multitude of cell types spanning different microenvironments. Mass spectrometry imaging (MSI) has the potential to identify metabolic patterns within the tumor ecosystem and surrounding tissues, but conventional workflows have not yet fully integrated the breadth of experimental techniques in metabolomics. Here, we combine MSI, stable isotope labeling, and a spatial variant of Isotopologue Spectral Analysis to map distributions of metabolite abundances, nutrient contributions, and metabolic turnover fluxes across the brains of mice harboring GL261 glioma, a widely used model for glioblastoma. When integrated with MSI, the combination of ion mobility, desorption electrospray ionization, and matrix assisted laser desorption ionization reveals alterations in multiple anabolic pathways. De novo fatty acid synthesis flux is increased by approximately 3-fold in glioma relative to surrounding healthy tissue. Fatty acid elongation flux is elevated even higher at 8-fold relative to surrounding healthy tissue and highlights the importance of elongase activity in glioma.PMID:37208361 | DOI:10.1038/s41467-023-38403-x

Fish Shellfish Immunol. 2023 May 17:108840. doi: 10.1016/j.fsi.2023.108840. Online ahead of print.ABSTRACTGrass carp reovirus genotype Ⅱ (GCRV Ⅱ) causes hemorrhagic disease in a variety fish, seriously affecting the aquaculture industry in China. However, the pathogenesis of GCRV Ⅱ is unclear. Rare minnow is an ideal model organism to study the pathogenesis of GCRV Ⅱ. Herein, we applied liquid chromatography-tandem mass spectrometry metabolomics to investigate metabolic responses in the spleen and hepatopancreas of rare minnow injected with virulent GCRV Ⅱ isolate DY197 and attenuated isolate QJ205. Results indicated that marked metabolic changes were identified in both the spleen and hepatopancreas after GCRV Ⅱ infection, and the virulent DY197 strain induced more significantly different metabolites (SDMs) than the attenuated QJ205 strain. Moreover, most SDMs were downregulated in the spleen and tend to be upregulated in hepatopancreas. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that tissue-specific metabolic responses were identified after viruses infection, and the virulent DY197 strain induced more SDMs involved in amino acid metabolism in the spleen, especially the tryptophan metabolism, cysteine and methionine metabolism, which were essential for immune regulation in host; Meanwhile, nucleotide metabolism, protein synthesis and metabolism related pathways were enriched in the hepatopancreas by both virulent and attenuated strains. Our findings revealed the large scale metabolic alterations in rare minnow in response to attenuated and virulent GCRV Ⅱ infection, which will lead to a better understanding of the pathogenesis of viruses and host-pathogens interactions.PMID:37207884 | DOI:10.1016/j.fsi.2023.108840