PubMed

Metabolomics. 2022 Nov 5;18(11):88. doi: 10.1007/s11306-022-01950-3.ABSTRACTINTRODUCTION: Earliness of tuberisation and the quality of potato tubers are important traits in potato breeding. The qualitative traits rely on the metabolite profile of tubers, which are storage organs and net importers of assimilates. Thus, the quality of tubers largely depends on the metabolites transported from leaves to developing tubers.OBJECTIVES: To test the influence of canopy on the quality of tubers by metabolite profiling of tubers of an early- and a late-maturing potato line and their grafts.METHODS: Potatoes were grown under greenhouse conditions, grafted and the tubers harvested at the end of the scions' vegetation period. Metabolite profiling of freshly harvested tubers was performed using gas chromatography coupled with mass spectrometry. Statistical analyses were applied to determine the significant differences between the different tubers.RESULTS: 99 metabolites were identified and an additional 181 peaks detected in chromatograms, out of which 186 were polar and 94 non-polar compounds. The concentrations of 113 metabolites were significantly different in the tubers from the early-maturing CE3130 and the late-maturing CE3027 line. Hetero-grafting resulted in considerable changes in the metabolite content of tubers. Especially, the effect of CE3027 on the metabolite composition of tubers formed on CE3130 rootstocks was readily apparent. Nevertheless, many compounds were present at similar levels in the tubers of hetero-grafted plants as was found in the tubers of their scion counterparts.CONCLUSION: Hetero-grafting resulted in many compounds at similar concentrations in rootstock tubers as in scion tubers suggesting that these are transported from the source leaves to tubers.PMID:36334159 | DOI:10.1007/s11306-022-01950-3

Glia. 2022 Nov 5. doi: 10.1002/glia.24283. Online ahead of print.ABSTRACTThe human macula is a highly specialized retinal region with pit-like morphology and rich in cones. How Müller cells, the principal glial cell type in the retina, are adapted to this environment is still poorly understood. We compared proteomic data from cone- and rod-rich retinae from human and mice and identified different expression profiles of cone- and rod-associated Müller cells that converged on pathways representing extracellular matrix and cell adhesion. In particular, epiplakin (EPPK1), which is thought to play a role in intermediate filament organization, was highly expressed in macular Müller cells. Furthermore, EPPK1 knockout in a human Müller cell-derived cell line led to a decrease in traction forces as well as to changes in cell size, shape, and filopodia characteristics. We here identified EPPK1 as a central molecular player in the region-specific architecture of the human retina, which likely enables specific functions under the immense mechanical loads in vivo.PMID:36334068 | DOI:10.1002/glia.24283

Environ Microbiol. 2022 Nov 4. doi: 10.1111/1462-2920.16271. Online ahead of print.ABSTRACTThe comprehension of microbial interactions is one of the key challenges in marine microbial ecology. This study focused on exploring chemical interactions between the toxic dinoflagellate Prorocentrum lima and a filamentous fungal species, Aspergillus pseudoglaucus, which has been isolated from the microalgal culture. Such interspecies interactions are expected to occur even though they were rarely studied. Here, a co-culture system was designed in a dedicated microscale marine-like condition. This system allowed to explore microalgal-fungal physical and metabolic interactions in presence and absence of the bacterial consortium. Microscopic observation showed an unusual physical contact between the fungal mycelium and dinoflagellate cells. To delineate specialized metabolome alterations during microalgal-fungal co-culture metabolomes were monitored by high-performance liquid chromatography coupled to high-resolution mass spectrometry. In-depth multivariate statistical analysis using dedicated approaches highlighted (1) the metabolic alterations associated with microalgal-fungal co-culture, and (2) the impact of associated bacteria in microalgal metabolome response to fungal interaction. Unfortunately, only a very low number of highlighted features were fully characterised. However, an up-regulation of the dinoflagellate toxins okadaic acid and dinophysistoxin 1 was observed during co-culture in supernatants. Such results highlight the importance to consider microalgal-fungal interactions in the study of parameters regulating toxin production. This article is protected by copyright. All rights reserved.PMID:36333915 | DOI:10.1111/1462-2920.16271

Sci Rep. 2022 Nov 4;12(1):18663. doi: 10.1038/s41598-022-18957-4.ABSTRACTPediatric liver transplantation rejection affects 20% of children. Currently, liver biopsy, expensive and invasive, is the best method of diagnosis. Discovery and validation of clinical biomarkers from blood or other biospecimens would improve clinical care. For this study, stored plasma samples were utilized from two cross-sectional cohorts of liver transplant patients at Children's Healthcare of Atlanta. High resolution metabolic profiling was completed using established methods. Children with (n = 18) or without (n = 25) acute cellular rejection were included in the analysis (n = 43 total). The mean age of these racially diverse cohorts ranged from 12.6 years in the rejection group and 13.6 years in the no rejection group. Linear regression provided 510 significantly differentiating metabolites between groups, and OPLS-DA showed 145 metabolites with VIP > 2. A total of 95 overlapping significant metabolites between OPLS-DA and linear regression analyses were detected. Pathway analysis (p < 0.05) showed bile acid biosynthesis and tryptophan metabolism as the top two differentiating pathways. Network analysis also identified tryptophan and clustered with liver enzymes and steroid use. We conclude metabolic profiling of plasma from children with acute liver transplant rejection demonstrates > 500 significant metabolites. This result suggests that development of a non-invasive biomarker-based test is possible for rejection screening.PMID:36333377 | DOI:10.1038/s41598-022-18957-4

Nat Commun. 2022 Nov 4;13(1):6656. doi: 10.1038/s41467-022-34537-6.ABSTRACTLiquid chromatography - mass spectrometry (LC-MS) based untargeted metabolomics allows to measure both known and unknown metabolites in the metabolome. However, unknown metabolite annotation is a major challenge in untargeted metabolomics. Here, we develop an approach, namely, knowledge-guided multi-layer network (KGMN), to enable global metabolite annotation from knowns to unknowns in untargeted metabolomics. The KGMN approach integrates three-layer networks, including knowledge-based metabolic reaction network, knowledge-guided MS/MS similarity network, and global peak correlation network. To demonstrate the principle, we apply KGMN in an in vitro enzymatic reaction system and different biological samples, with ~100-300 putative unknowns annotated in each data set. Among them, >80% unknown metabolites are corroborated with in silico MS/MS tools. Finally, we validate 5 metabolites that are absent in common MS/MS libraries through repository mining and synthesis of chemical standards. Together, the KGMN approach enables efficient unknown annotations, and substantially advances the discovery of recurrent unknown metabolites for common biological samples from model organisms, towards deciphering dark matter in untargeted metabolomics.PMID:36333358 | DOI:10.1038/s41467-022-34537-6

BMJ Open. 2022 Nov 4;12(11):e062873. doi: 10.1136/bmjopen-2022-062873.ABSTRACTINTRODUCTION: To date, no pancreatic stump closure technique has been shown to be superior to any other in distal pancreatectomy. Although several studies have shown a trend towards better results in transection using a radiofrequency device (radiofrequency-assisted transection (RFT)), no randomised trial for this purpose has been performed to date. Therefore, we designed a randomised clinical trial, with the hypothesis that this technique used in distal pancreatectomies is superior in reducing clinically relevant postoperative pancreatic fistula (CR-POPF) than mechanical closures.METHODS AND ANALYSIS: TRANSPAIRE is a multicentre randomised controlled trial conducted in seven Spanish pancreatic centres that includes 112 patients undergoing elective distal pancreatectomy for any indication who will be randomly assigned to RFT or classic stapler transections (control group) in a ratio of 1:1. The primary outcome is the CR-POPF percentage. Sample size is calculated with the following assumptions: 5% one-sided significance level (α), 80% power (1-β), expected POPF in control group of 32%, expected POPF in RFT group of 10% and a clinically relevant difference of 22%. Secondary outcomes include postoperative results, complications, radiological evaluation of the pancreatic stump, metabolomic profile of postoperative peritoneal fluid, survival and quality of life. Follow-ups will be carried out in the external consultation at 1, 6 and 12 months postoperatively.ETHICS AND DISSEMINATION: TRANSPAIRE has been approved by the CEIM-PSMAR Ethics Committee. This project is being carried out in accordance with national and international guidelines, the basic principles of protection of human rights and dignity established in the Declaration of Helsinki (64th General Assembly, Fortaleza, Brazil, October 2013), and in accordance with regulations in studies with biological samples, Law 14/2007 on Biomedical Research will be followed. We have defined a dissemination strategy, whose main objective is the participation of stakeholders and the transfer of knowledge to support the exploitation of activities.REGISTRATION DETAILS: ClinicalTrials.gov Registry (NCT04402346).PMID:36332946 | DOI:10.1136/bmjopen-2022-062873

Mol Cell Proteomics. 2022 Nov 1:100438. doi: 10.1016/j.mcpro.2022.100438. Online ahead of print.ABSTRACTHuman pancreatic stellate cells (HPSCs) are an essential stromal component and mediators of pancreatic ductal adenocarcinoma (PDAC) progression. Small extracellular vesicles (sEVs) are membrane-enclosed nanoparticles involved in cell-to-cell communications and are released from stromal cells within PDAC. A detailed comparison of sEVs from normal pancreatic stellate cells (HPaStec) and from PDAC-associated stellate cells (HPSCs) remains a gap in our current knowledge regarding stellate cells and PDAC. We hypothesized there would be differences in sEVs secretion and protein expression that might contribute to PDAC biology. To test this hypothesis, we isolated sEVs using ultracentrifugation followed by characterization by electron microscopy and Nanoparticle Tracking Analysis. We report here our initial observations. First, HPSC cells derived from PDAC tumors secrete a higher volume of sEVs when compared to normal pancreatic stellate cells (HPaStec). Although our data revealed that both normal and tumor derived sEVs demonstrated no significant biological effect on cancer cells, we observed efficient uptake of sEVs by both normal and cancer epithelial cells. Additionally, intact membrane-associated proteins on sEVs were essential for efficient uptake. We then compared sEV proteins isolated from HPSCs and HPaStecs cells using liquid chromatography-tandem mass spectrometry. Most of the 1,481 protein groups identified were shared with the exosome database, ExoCarta. Eighty-seven protein groups were differentially expressed (selected by 2-fold difference and adjusted p value ≤ 0.05) between HPSC and HPaStec sEVs. Of note, HPSC sEVs contained dramatically more CSE1L (chromosome segregation 1-like protein), a described marker of poor prognosis in patients with pancreatic cancer. Based on our results, we have demonstrated unique populations of sEVs originating from stromal cells with PDAC and suggest that these are significant to cancer biology. Further studies should be undertaken to gain a deeper understanding that could drive novel therapy.PMID:36332889 | DOI:10.1016/j.mcpro.2022.100438

Food Chem. 2022 Oct 29;404(Pt B):134773. doi: 10.1016/j.foodchem.2022.134773. Online ahead of print.ABSTRACTLiupao tea is a dark tea with unique quality. Semi-finished Liupao tea with two different fermentation processes (traditional/tank) was analyzed to explain the chemical characteristics and taste quality. The content change rate of polyphenols, flavonoids, and theabrownin in traditional fermentation was approximately twice that in tank fermentation. Electronic tongue revealed that bitterness and astringency increased, whereas aftertaste-astringency decreased after fermentation. 36 compounds were identified as the biomarkers responsible for the metabolic changes caused by fermentation with significant decrements in catechins, catechin gallate, and α, α-trehalose, and significant increments in gallic acid content (VIP > 3; P < 0.05). In addition, 26 metabolites were identified to distinguish between tank and traditional fermentation, with correlation analysis indicating that catechin gallate, epicatechin and gallic acid accounting for the differences in taste between the two processes. This study provides a comprehensive insight into the chemical composition and sensory quality of different Liupao tea fermentations.PMID:36332583 | DOI:10.1016/j.foodchem.2022.134773

Cell Stem Cell. 2022 Nov 3;29(11):1580-1593.e7. doi: 10.1016/j.stem.2022.10.008.ABSTRACTAccumulating evidence demonstrates important roles for metabolism in cell fate determination. However, it is a challenge to assess metabolism at a spatial resolution that acknowledges both heterogeneity and cellular dynamics in its tissue microenvironment. Using a multi-omics platform to study cell-type-specific dynamics in metabolism in complex tissues, we describe the metabolic trajectories during nephrogenesis in the developing human kidney. Exploiting in situ analysis of isotopic labeling, a shift from glycolysis toward fatty acid β-oxidation was observed during the differentiation from the renal vesicle toward the S-shaped body and the proximal tubules. In addition, we show that hiPSC-derived kidney organoids are characterized by a metabolic immature phenotype that fails to use mitochondrial long-chain fatty acids for energy metabolism. Furthermore, supplementation of butyrate enhances tubular epithelial differentiation and maturation in cultured kidney organoids. Our findings highlight the relevance of understanding metabolic trajectories to efficiently guide stem cell differentiation.PMID:36332571 | DOI:10.1016/j.stem.2022.10.008

Phytomedicine. 2022 Oct 27;108:154527. doi: 10.1016/j.phymed.2022.154527. Online ahead of print.ABSTRACTBACKGROUND: The novel coronavirus pneumonia (COVID-19) has spread rapidly around the world. As a member against the epidemic, Qingfei Paidu Decoction (QFPDD) has been approved for the treatment of COVID-19 in China. However, its antiviral mechanism was still largely unclear.PURPOSE: An integrated strategy was used to explore the antiviral mechanisms of QFPDD in cold and damp environment, including pharmacokinetic (PK), network pharmacology, metabolomics and protein verification.METHODS: Firstly, the pharmacokinetic study of the prototype absorbed ingredients were analyzed by UHPLC-QqQ-MS. Secondly, the metabolomics analysis of the endogenous constituents was carried out. Based on the aforementioned results, an integrated network was constructed to identify the curative components, crucial endogenous differential metabolites and related pathways. Finally, the validation tests were implemented by molecular docking and western blotting (WB).RESULTS: According to the pharmacokinetic behaviors analysis of 31 components in vivo, the flavonoids presented more longer residence time and higher exposure compared with the other compounds. The efficacy and antiviral mechanism of QFPDD were verified by the poly-pharmacology, metabolomics, molecular docking and WB. For the occurrence of metabolic disorder, the change of amino acid transporters should not be neglected. Afterward, 8 curative compounds, 6 key genes and corresponding metabolic pathways were filtered by compound-reaction-enzyme-gene network. The molecular docking verified that the active ingredients bound to the relevant targets well.CONCLUSION: In the present study, an in vivo comprehensive pharmacokinetic behaviors of QFPDD was analyzed for the first time. The results illustrated that QFPDD could exhibit immune regulation, anti-infection, anti-inflammation and metabolic disorder to perform a corresponding therapeutic effect. Moreover, our findings highlighted the roles of amino acid transporters in the coronavirus infection situation.PMID:36332393 | DOI:10.1016/j.phymed.2022.154527

Proc Natl Acad Sci U S A. 2022 Nov 8;119(45):e2217609119. doi: 10.1073/pnas.2217609119. Epub 2022 Nov 4.NO ABSTRACTPMID:36331997 | DOI:10.1073/pnas.2217609119

J Agric Food Chem. 2022 Nov 4. doi: 10.1021/acs.jafc.2c03080. Online ahead of print.ABSTRACTEfficient characterization of xenobiotic metabolites and their dynamics in a changing complex matrix remains difficult. Herein, we proposed a time-series-dependent global data filtering strategy for the rapid and comprehensive characterization of xenobiotic metabolites and their dynamic variation based on metabolome data. A set of data preprocessing methods was used to screen potential xenobiotic metabolites, considering the differences between the treated and control groups and the fluctuations over time. To further identify metabolites of the target, an in-house accurate mass database was constructed by potential metabolic pathways and applied. Taking the extract of Ginkgo biloba (EGB) co-incubated with gut microbiota as an example, 107 compounds were identified as flavonoid-derived metabolites (including 67 original from EGB and 40 new) from 7468 ions. Their temporal metabolic profiles and regularities were also investigated. This study provided a systematic and feasible method to elucidate and profile xenobiotic metabolism.PMID:36331925 | DOI:10.1021/acs.jafc.2c03080

Clin Chem. 2022 Nov 4:hvac172. doi: 10.1093/clinchem/hvac172. Online ahead of print.ABSTRACTBACKGROUND: We examined the interplay of apolipoprotein B (apoB) and LDL particle size, approximated by the LDL-cholesterol (LDL-C)/apoB ratio, on the risk of new-onset coronary heart disease (CHD).METHODS: Participants without cardiovascular disease from the UK Biobank (UKB; n = 308 182), the Women's Health Study (WHS; n = 26 204), and the Framingham Heart Study (FHS; n = 2839) were included. Multivariable Cox models were used to assess the relationship between apoB and LDL-C/apoB ratio and incidence of CHD (14 994 events). Our analyses were adjusted for age, sex (except WHS), HDL-cholesterol (HDL-C), systolic blood pressure, antihypertensive treatment, diabetes, and smoking.RESULTS: In all 3 studies, there was a strong positive correlation between apoB and LDL-C (correlation coefficients r = 0.80 or higher) and a weak inverse correlation of apoB with LDL-C/apoB ratio (-0.28 ≤ r ≤ -0.14). For all 3 cohorts, CHD risk was higher for higher levels of apoB. Upon multivariable adjustment, the association between apoB and new-onset CHD remained robust and statistically significant in all 3 cohorts with hazard ratios per 1 SD (95% CI): 1.24 (1.22-1.27), 1.33 (1.20-1.47), and 1.24 (1.09-1.42) for UKB, WHS, and FHS, respectively. However, the association between LDL-C/apoB and CHD was statistically significant only in the FHS cohort: 0.78 (0.64-0.94).CONCLUSIONS: Our analysis confirms that apoB is a strong risk factor for CHD. However, given the null association in 2 of the 3 studies, we cannot confirm that cholesterol-depleted LDL particles are substantially more atherogenic than cholesterol-replete particles. These results lend further support to routine measurement of apoB in clinical care.PMID:36331823 | DOI:10.1093/clinchem/hvac172

Environ Health Perspect. 2022 Nov;130(11):117003. doi: 10.1289/EHP11360. Epub 2022 Nov 4.ABSTRACTBACKGROUND: Perfluorooctane sulfonate (PFOS) is a persistent environmental pollutant that has become a significant concern around the world. Exposure to PFOS may alter gut microbiota and liver metabolic homeostasis in mammals, thereby increasing the risk of cardiometabolic diseases. Diets high in soluble fibers can ameliorate metabolic disease risks.OBJECTIVES: We aimed to test the hypothesis that soluble fibers (inulin or pectin) could modulate the adverse metabolic effects of PFOS by affecting microbe-liver metabolism and interactions.METHODS: Male C57BL/6J mice were fed an isocaloric diet containing different fibers: a) inulin (soluble), b) pectin (soluble), or c) cellulose (control, insoluble). The mice were exposed to PFOS in drinking water (3μg/g per day) for 7 wk. Multi-omics was used to analyze mouse liver and cecum contents.RESULTS: In PFOS-exposed mice, the number of differentially expressed genes associated with atherogenesis and hepatic hyperlipidemia were lower in those that were fed soluble fiber than those fed insoluble fiber. Shotgun metagenomics showed that inulin and pectin protected against differences in microbiome community in PFOS-exposed vs. control mice. It was found that the plasma PFOS levels were lower in inulin-fed mice, and there was a trend of lower liver accumulation of PFOS in soluble fiber-fed mice compared with the control group. Soluble fiber intake ameliorated the effects of PFOS on host hepatic metabolism gene expression and cecal content microbiome structure.DISCUSSIONS: Results from metabolomic, lipidomic, and transcriptomic studies suggest that inulin- and pectin-fed mice were less susceptible to PFOS-induced liver metabolic disturbance, hepatic lipid accumulation, and transcriptional changes compared with control diet-fed mice. Our study advances the understanding of interaction between microbes and host under the influences of environmental pollutants and nutrients. The results provide new insights into the microbe-liver metabolic network and the protection against environmental pollutant-induced metabolic diseases by high-fiber diets. https://doi.org/10.1289/EHP11360.PMID:36331819 | DOI:10.1289/EHP11360

Fish Physiol Biochem. 2022 Nov 4. doi: 10.1007/s10695-022-01135-8. Online ahead of print.NO ABSTRACTPMID:36331695 | DOI:10.1007/s10695-022-01135-8

J Nat Prod. 2022 Nov 4. doi: 10.1021/acs.jnatprod.2c00637. Online ahead of print.ABSTRACTMyxobacteria have proven to be a rich source of natural products, but their biosynthetic potential seems to be underexplored given the high number of biosynthetic gene clusters present in their genomes. In this study, a truncated ajudazol biosynthetic gene cluster in Cystobacter sp. SBCb004 was identified using mutagenesis and metabolomics analyses and a set of novel ajudazols (named ajudazols C-J, 3-10, respectively) were detected and subsequently isolated. Their structures were elucidated using comprehensive HR-MS and NMR spectroscopy. Unlike the known ajudazols A (1) and B (2), which utilize acetyl-CoA as the biosynthetic starter unit, these novel ajudazols were proposed to incorporate 3,3-dimethylacrylyl CoA as the starter. Ajudazols C-J (3-10, respectively) are characterized by varying degrees of hydroxylation, desaturation, and different glycosylation patterns. Two P450-dependent enzymes and one glycosyltransferase are shown to be responsible for the hydroxylation at C-8, the desaturation at C-15 and C-33, and the transfer of a d-β-glucopyranose, respectively, based on mutagenesis results. One of the cytochrome P450-dependent enzymes and the glycosyltransferase were found to be encoded by genes located outside the biosynthetic gene cluster. Ajudazols C-H (3-8, respectively) exhibit cytotoxicity against various cancer cell lines.PMID:36331369 | DOI:10.1021/acs.jnatprod.2c00637

Scand J Med Sci Sports. 2022 Nov 4. doi: 10.1111/sms.14261. Online ahead of print.ABSTRACTOBJECTIVE: Physical activity benefits cardiometabolic health, but little is known about its detailed links with serum lipoproteins, amino acids, and glucose metabolism at young age. We therefore studied the association of physical activity with a comprehensive metabolic profile measured repeatedly in adolescence.METHODS: The cohort is derived from the longitudinal Special Turku Coronary Risk Factor Intervention Project. At ages 13, 15, 17, and 19 years, data on physical activity was collected by a questionnaire, and circulating metabolic measures were quantified by nuclear magnetic resonance metabolomics from repeatedly assessed serum samples (age 13:n=503, 15:n=472, 17:n=466, and 19:n=361).RESULTS: Leisure-time physical activity (LTPA;MET h/wk) was directly associated with concentrations of polyunsaturated fatty acids, and inversely with the ratio of monounsaturated fatty acids to total fatty acids (-0.006SD; [-0.008, -0.003]; p<0.0001). LTPA was inversely associated with very-low-density lipoprotein (VLDL) particle concentration (-0.003SD; [-0.005, -0.001]; p=0.002) and VLDL particle size (-0.005SD; [-0.007, -0.003]; p<0.0001). LTPA showed direct association with the particle concentration and size of high-density lipoprotein (HDL), and HDL cholesterol concentration (0.004SD; [0.002, 0.006]; p<0.0001). Inverse associations of LTPA with triglyceride and total lipid concentrations in large to small sized VLDL subclasses were found. Weaker associations were seen for other metabolic measures including inverse associations with concentrations of lactate, isoleucine, glycoprotein acetylation, and a direct association with creatinine concentration. The results remained after adjusting for body mass index and proportions of energy intakes from macronutrients.CONCLUSIONS: Physical activity during adolescence is beneficially associated with the metabolic profile including novel markers. The results support recommendations on physical activity during adolescence to promote health and possibly reduce future disease risks.PMID:36331352 | DOI:10.1111/sms.14261

Toxicol Sci. 2022 Nov 4:kfac117. doi: 10.1093/toxsci/kfac117. Online ahead of print.ABSTRACTAsthma is a common chronic respiratory disease exacerbated by multiple environmental factors. Acute ozone exposure has previously been implicated in airway inflammation, airway hyperreactivity, and other characteristics of asthma, which may be attributable to altered sphingolipid metabolism. This study tested the hypothesis that acute ozone exposure alters sphingolipid metabolism within the lung, which contributes to exacerbations in characteristics of asthma in allergen-sensitized mice. Adult male and female BALB/c mice were sensitized intranasally to house dust mite allergen (HDM) on days 1, 3, and 5 and challenged on days 12-14. Mice were exposed to ozone following each HDM challenge for 6 hr./day. Bronchoalveolar lavage, lung lobes, and microdissected lung airways were collected for metabolomics analysis (N = 8/sex/group). Another subset of mice underwent methacholine challenge using a forced oscillation technique to measure airway resistance (N = 6/sex/group). Combined HDM and ozone exposure in male mice synergistically increased airway hyperreactivity that was not observed in females and was accompanied by increased airway inflammation and eosinophilia relative to control mice. Importantly, glycosphingolipids were significantly increased following combined HDM and ozone exposure relative to controls in both male and female airways, which was also associated with both airway resistance and eosinophilia. However, 15 glycosphingolipid species were increased in females compared to only 6 in males, which was concomitant with significant associations between glycosphingolipids and airway resistance that ranged from R2= 0.33-0.51 for females and R2= 0.20-0.34 in male mice. These observed sex differences demonstrate that glycosphingolipids potentially serve to mitigate exacerbations in characteristics of allergic asthma.PMID:36331340 | DOI:10.1093/toxsci/kfac117

Chembiochem. 2022 Nov 4. doi: 10.1002/cbic.202200584. Online ahead of print.ABSTRACTCoenzyme A (CoA) thioesters are formed during anabolic and catabolic reactions in every organism. Degradation pathways of growth-supporting substrates in bacteria can be predicted by differential proteogenomic studies. Direct detection of proposed metabolites such as CoA thioesters by high-performance liquid chromatography coupled with high-resolution mass spectrometry can confirm the reaction sequence and demonstrate the activity of these degradation pathways. In the metabolomes of the anaerobic sulfate-reducing bacterium Desulfobacula toluolica Tol2T grown with different substrates various CoA thioesters, derived from amino acid, fatty acid or alcohol metabolism, have been detected. Additionally, the cell extracts of this bacterium revealed a number of CoA analogues with molecular masses increased by 1 atomic mass unit. By comparing the chromatographic and mass spectrometric properties of synthetic reference standards with those of compounds detected in cell extracts of D. toluolica Tol2T and by performing co-injection experiments, these analogues were identified as inosino-CoAs. These CoA thioesters contain inosine instead of adenosine as the nucleoside. To the best of our knowledge, this finding represents the first detection of naturally occurring inosino-CoA analogues.PMID:36331165 | DOI:10.1002/cbic.202200584

Toxicology. 2022 Oct 27;482:153367. doi: 10.1016/j.tox.2022.153367. Online ahead of print.ABSTRACTCyadox, a potential antimicrobial growth promoter, has been widely studied and prospected to be used as an additive in livestock and poultry feed. Although high cyadox exposure has been reported to cause toxicity, the exact metabolic effects are not fully understood. Our study aim is to evaluate the metabolic effects of cyadox using comprehensive methods including serum clinical chemical test, histopathology analysis, metabolomics, and transcriptomics profile analysis. One single acute dosage over 7-day course and one subchronic 90-day dietary ingestion of cyadox intervention were conducted on the Wistar rats separately. Dose-dependent alterations were shown in the metabolism of the urine, kidney, plasma, and liver by metabolomics analysis. We further investigated gene expressions of the liver administered with high dose of cyadox for 12 weeks. Top sixty-six differentially expressed genes involved in the pathways, including xenobiotic (cyadox) metabolism, lipid metabolism, energy metabolism, nucleic acid metabolic process, inflammatory response, and response to the oxidative stress, which were in concordance with these metabolic alternations. Our study provided a comprehensive information on how cyadox modulates the metabolism and gene expressions, which is vital when considering the safe application of cyadox.PMID:36330926 | DOI:10.1016/j.tox.2022.153367