PubMed

Related Articles EV-associated miRNAs from pleural lavage as potential diagnostic biomarkers in lung cancer. Sci Rep. 2019 10 21;9(1):15057 Authors: Roman-Canal B, Moiola CP, Gatius S, Bonnin S, Ruiz-Miró M, González E, Ojanguren A, Recuero JL, Gil-Moreno A, Falcón-Pérez JM, Ponomarenko J, Porcel JM, Matias-Guiu X, Colas E Abstract Lung cancer is the leading cause of cancer-related deaths among men and women in the world, accounting for the 25% of cancer mortality. Early diagnosis is an unmet clinical issue. In this work, we focused to develop a novel approach to identify highly sensitive and specific biomarkers by investigating the use of extracellular vesicles (EVs) isolated from the pleural lavage, a proximal fluid in lung cancer patients, as a source of potential biomarkers. We isolated EVs by ultracentrifuge method from 25 control pleural fluids and 21 pleural lavages from lung cancer patients. Analysis of the expression of EV-associated miRNAs was performed using Taqman OpenArray technology through which we could detect 288 out of the 754 miRNAs that were contained in the OpenArray. The differential expression analysis yielded a list of 14 miRNAs that were significantly dysregulated (adj. p-value < 0.05 and logFC lower or higher than 3). Using Machine Learning approach we discovered the lung cancer diagnostic biomarkers; miRNA-1-3p, miRNA-144-5p and miRNA-150-5p were found to be the best by accuracy. Accordance with our finding, these miRNAs have been related to cancer processes in previous studies. This results opens the avenue to the use of EV-associated miRNA of pleural fluids and lavages as an untapped source of biomarkers, and specifically, identifies miRNA-1-3p, miRNA-144-5p and miRNA 150-5p as promising biomarkers of lung cancer diagnosis. PMID: 31636323 [PubMed - indexed for MEDLINE]

28 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/10/28PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

28 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/10/28PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

28 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/10/27PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Comparison of MS2, synchronous precursor selection MS3, and real-time search MS3 methodologies for lung proteomes of hydrogen sulfide treated swine. Anal Bioanal Chem. 2020 Oct 25;: Authors: Fu Q, Liu Z, Bhawal R, Anderson ET, Sherwood RW, Yang Y, Thannhauser T, Schroyen M, Tang X, Zhang H, Zhang S Abstract Tandem mass tags (TMTs) have increasingly become an attractive technique for global proteomics. However, its effectiveness for multiplexed quantitation by traditional tandem mass spectrometry (MS2) suffers from ratio distortion. Synchronous precursor selection (SPS) MS3 has been widely accepted for improved quantitation accuracy, but concurrently decreased proteome coverage. Recently, a Real-Time Search algorithm has been integrated with the SPS MS3 pipeline (RTS MS3) to provide accurate quantitation and improved depth of coverage. In this mechanistic study of the impact of exposure to hydrogen sulfide (H2S) on the respiration of swine, we used TMT-based comparative proteomics of lung tissues from control and H2S-treated subjects as a test case to evaluate traditional MS2, SPS MS3, and RTS MS3 acquisition methods on both the Orbitrap Fusion and Orbitrap Eclipse platforms. Comparison of the results obtained by the MS2 with those of SPS MS3 and RTS MS3 methods suggests that the MS3-driven quantitative strategies provided a more accurate global-scale quantitation; however, only RTS MS3 provided proteomic coverage that rivaled that of traditional MS2 analysis. RTS MS3 not only yields more productive MS3 spectra than SPS MS3 but also appears to focus the analysis more effectively on unique peptides. Furthermore, pathway enrichment analyses of the H2S-altered proteins demonstrated that an additional apoptosis pathway was discovered exclusively by RTS MS3. This finding was verified by RT-qPCR, western blotting, and TUNEL staining experiments. We conclude that RTS MS3 workflow enables simultaneous improvement of quantitative accuracy and proteome coverage over alternative approaches (MS2 and SPS MS3). Graphical abstract. PMID: 33099676 [PubMed - as supplied by publisher]

Vitreous metabolomics profiling of proliferative diabetic retinopathy. Diabetologia. 2020 Oct 25;: Authors: Tomita Y, Cagnone G, Fu Z, Cakir B, Kotoda Y, Asakage M, Wakabayashi Y, Hellström A, Joyal JS, Talukdar S, Smith LEH, Usui Y Abstract AIMS/HYPOTHESIS: Proliferative diabetic retinopathy (PDR) with retinal neovascularisation (NV) is a leading cause of vision loss. This study identified a set of metabolites that were altered in the vitreous humour of PDR patients compared with non-diabetic control participants. We corroborated changes in vitreous metabolites identified in prior studies and identified novel dysregulated metabolites that may lead to treatment strategies for PDR. METHODS: We analysed metabolites in vitreous samples from 43 PDR patients and 21 non-diabetic epiretinal membrane control patients from Japan (age 27-80 years) via ultra-high-performance liquid chromatography-mass spectrometry. We then investigated the association of a novel metabolite (creatine) with retinal NV in mouse oxygen-induced retinopathy (OIR). Creatine or vehicle was administered from postnatal day (P)12 to P16 (during induced NV) via oral gavage. P17 retinas were quantified for NV and vaso-obliteration. RESULTS: We identified 158 metabolites in vitreous samples that were altered in PDR patients vs control participants. We corroborated increases in pyruvate, lactate, proline and allantoin in PDR, which were identified in prior studies. We also found changes in metabolites not previously identified, including creatine. In human vitreous humour, creatine levels were decreased in PDR patients compared with epiretinal membrane control participants (false-discovery rate <0.001). We validated that lower creatine levels were associated with vascular proliferation in mouse retina in the OIR model (p = 0.027) using retinal metabolomics. Oral creatine supplementation reduced NV compared with vehicle (P12 to P16) in OIR (p = 0.0024). CONCLUSIONS/INTERPRETATION: These results suggest that metabolites from vitreous humour may reflect changes in metabolism that can be used to find pathways influencing retinopathy. Creatine supplementation could be useful to suppress NV in PDR. Graphical abstract. PMID: 33099660 [PubMed - as supplied by publisher]

Serum Spermidine as a Novel Potential Predictor for Fragility Fractures. J Clin Endocrinol Metab. 2020 Oct 25;: Authors: Kong SH, Kim JH, Shin CS Abstract CONTEXT: Metabolomics is an emerging tool that provides insights into the dynamics of phenotypic changes. It is a potential method for the discovery of novel serum markers of fracture. OBJECTIVE: To identify metabolite parameters that can be used as a proxy for osteoporotic fracture risk. DESIGN: Prospective study based on the Ansung cohort in Korea. SETTING: The general community. PARTICIPANTS: 1,504 participants with metabolomic analyses. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Fragility fractures. RESULTS: We measured 135 baseline metabolite profiles in fasting serum of the participants. The participants had a mean age of 60.2 years and comprised of 585 (38.9%) men. During a mean 9-year follow-up, 112 osteoporotic fracture events occurred. Of all metabolites measured, only serum spermidine concentrations were positively associated with the risk of fracture (hazard ratio [HR] per 1 μM of spermidine 1.35, 95% confidence interval [CI]= 1.03-1.65, p=0.020) after adjustments for age, sex, BMI, diabetes, hypertension, smoking status, previous fracture history, and baseline tibial quantitative ultrasound. Participants with spermidine concentrations >1.57 μM had a 2.2-fold higher risk of fractures (95% CI 1.08-4.51, p=0.030) compared to those with concentrations ≤1.57 μM after adjustment. In a subgroup analysis, women with baseline spermidine concentrations >1.57 μM also had a 2.4-fold higher risk of fracture than those with concentrations ≤1.57 μM (95% CI 1.02-5.48, p=0.047). CONCLUSIONS: Increased baseline spermidine concentrations were associated with a risk of osteoporotic fracture during a mean 9-year follow-up. The biological significance of the metabolites in the musculoskeletal system could be a subject for future studies. PMID: 33099626 [PubMed - as supplied by publisher]

Metabolomic characteristics of hepatotoxicity in rats induced by silica nanoparticles. Ecotoxicol Environ Saf. 2020 Oct 21;208:111496 Authors: Sun M, Zhang J, Liang S, Du Z, Liu J, Sun Z, Duan J Abstract Silica nanoparticles (SiNPs) have become one of the most widely studied nanoparticles in nanotechnology for environmental health and safety. Although many studies have devoted to evaluating the hepatotoxicity of SiNPs, it is currently impossible to predict the extent of liver lipid metabolism disorder by identifying changes in metabolites. In the present study, 40 male Sprague-Dawley (SD) rats were randomly divided into control group and 3 groups with different doses (1.8 mg/kg body weight (bw), 5.4 mg/kg bw, 16.2 mg/kg bw), receiving intratracheal instillation of SiNPs. Liver tissue was taken for lipid level analysis, and serum was used for blood biochemical analysis. Then, the metabolites changes of liver tissue in rats were systematically analyzed using 1H nuclear magnetic resonance (1H NMR) techniques in combination with multivariate statistical analysis. SiNPs induced serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglyceride (TG) elevation in treated groups; TG and low-density lipoprotein cholesterol (LDL-C) were significantly higher in SiNPs-treated groups of high-dose, however high-density lipoprotein cholesterol (HDL-C) showed a declining trend in liver tissue. The orthogonal partial least squares discriminant analysis (OPLS-DA) scores plots revealed different metabolic profiles between control and high-dose group (Q2 =0.495, R2Y=0.802, p = 0.037), and a total of 11 differential metabolites. Pathway analysis indicated that SiNPs treatment mainly affected 10 metabolic pathways including purine metabolism, glucose-alanine cycle and metabolism of various amino acids such as glutamate, cysteine and aspartate (impact value>0.1, false discovery rate (FDR)< 0.05). The result indicated that exposure to SiNPs caused liver lipid metabolism disorder in rats, the biochemical criterions related to lipid metabolism changed significantly. The obviously changed metabolomics in SiNPs-treated rats mostly occurred in amino acids, organic acids and nucleosides. PMID: 33099137 [PubMed - as supplied by publisher]

Loss of protein kinase D activity reveals redundancy in cardiac glucose metabolism and preserves cardiac function in obesity. Mol Metab. 2020 Oct 21;:101105 Authors: De Jong KA, Hall LG, Renton MC, Connor T, Martin SD, Kowalski GM, Shaw CS, Bruce CR, Howlett KF, McGee SL Abstract OBJECTIVE: Protein kinase D (PKD) signalling has been implicated in stress-induced cardiac remodelling and function, as well as metabolic processes including contraction-mediated cardiac glucose uptake. More recently, PKD has emerged as a nutrient sensing kinase that is activated in high-lipid environments, such as in obesity. However, the role of PKD signalling in cardiac glucose metabolism and in cardiac function, in both normal and obese conditions, remains unknown. METHODS: A cardiac-specific and inducible dominant negative (DN) PKD mouse model was developed. Echocardiography was used to assess cardiac function, while metabolic phenotyping was performed, including stable isotope metabolomics on cardiac tissue, in mice fed either regular chow, or a high fat diet (43% calories from fat). RESULTS: Cardiac PKD activity was reduced by ∼90%, following DN PKD induction in adult mice. These mice had impaired basal cardiac glucose clearance, suggesting impaired contraction-mediated glucose uptake, but normal cardiac function. In obesity studies, indices of systolic function were reduced in Control mice, but not in cardiac DN PKD mice. Using targeted stable isotope metabolomics analyses, no differences in glucose flux through glycolysis or the TCA cycle were observed between groups. CONCLUSIONS: These data show that PKD contributes to cardiac dysfunction in obesity and highlight the redundancy in cardiac glucose metabolism that maintain cardiac glucose flux in vivo. These data suggest that impairments in contraction-mediated glucose uptake are unlikely to drive cardiac dysfunction in both normal and metabolic disease states. PMID: 33099046 [PubMed - as supplied by publisher]

The associations of oxidized lipoprotein lipids with lipoprotein subclass particle concentrations and their lipid compositions. The Cardiovascular Risk in Young Finns Study. Free Radic Biol Med. 2020 Oct 21;: Authors: Kresanov P, Mykkänen J, Ahotupa M, Ala-Korpela M, Juonala M, Kaikkonen J, Kähönen M, Lehtimäki T, Vasankari T, Viikari J, Raitakari OT Abstract OBJECTIVE: Oxidation of low-density lipoprotein (LDL) may promote atherosclerosis, whereas the reverse transport of oxidized lipids by high-density lipoprotein (HDL) may contribute to atheroprotection. To provide insights into the associations of lipoprotein lipid oxidation markers with lipoprotein subclasses at the population level, we investigated the associations of oxidized HDL lipids (oxHDLlipids) and oxidized LDL lipids (oxLDLlipids) with lipoprotein subclasses in a population-based cross-sectional study of 1395 Finnish adults ages 24-39 years. METHODS: The analysis of oxidized lipids was based on the determination of the baseline level of conjugated dienes in lipoprotein lipids. A high-throughput nuclear magnetic resonance (NMR) platform was used to quantify circulating lipoprotein subclass concentrations and analyze their lipid compositions. RESULTS: OxHDLlipids were mainly not associated with lipoprotein subclass lipid concentrations and lipid composition after adjustment for Apolipoprotein-A1 (Apo-A1), waist circumference and age. OxLDLlipids were associated with several markers of lipoprotein subclass lipid concentrations and composition after adjustment for Apolipoprotein-B (Apo-B), age and waist circumference. Several measures of HDL and LDL subclasses, including phospholipid and triglyceride composition, associated directly with oxLDLlipids. Cholesterol ester and free cholesterol composition in HDL and LDL associated inversely with oxLDLlipids. CONCLUSION: We conclude that these results do not support the idea that HDL´s particle size or composition would reflect its functional capacity in the reverse transport of oxidized lipids. On the contrary, oxLDLlipids were associated with the entire lipoprotein subclass profile, including numerous associations with the compositional descriptors of the particles. This is in line with the suggested role of LDL oxidation in atherogenesis. PMID: 33098999 [PubMed - as supplied by publisher]

The water expelling effect evaluation of 3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol and ingenol on H22 mouse hepatoma ascites model and their content differences analysis in Euphorbia kansui before and after stir-fried with vinegar by UPLC. J Ethnopharmacol. 2020 Oct 21;:113507 Authors: Zhang Q, Ju YH, Zhang Y, Wang K, Zhang M, Chen PD, Yao WF, Tang YP, Wu JH, Zhang L Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Malignant ascites (MA) effusion is mainly caused by hepatocellular, ovarian, and breast cancer etc. It has been reported that Euphorbia kansui (EK), the root of Euphorbia kansui S.L.Liou ex S.B.Ho, possessing a therapeutic effect on MA. However, the clinical applications of EK are seriously restricted for its severe toxicity. Although studies demonstrated that vinegar-processing can reduce the toxicity and retain the water expelling effect of EK, its specific mechanism remains unknown. AIM OF THE STUDY: This study aims to explore the underlying mechanisms of toxicity reduction without compromising the pharmacological effects of EK stir-fried with vinegar (VEK). MATERIALS AND METHODS: 3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol (3-O-EZ), a major diterpenoid of EK, could convert into ingenol after processing EK with vinegar. The H22 mouse hepatoma ascites model was replicated, and were given 3-O-EZ and ingenol seven days (110.14, 50.07 and 27.54 mg/kg). The histopathological observation, serum liver enzymes, serum Renin-Angiotensin-Aldosterone System (RAAS) levels, ascites volumes, pro-inflammatory cytokines levels and H22 cells apoptosis in ascites were examined. Then the intestine (Aquaporin 8, AQP8) and kidney (Aquaporin 2, AQP2; Vasopressin type 2 receptor, V2R) protein expression were detected, as well as the metabolomics of serum were analyzed. Finally, the content of 3-O-EZ and ingenol in EK and VEK were investigated. RESULTS: 3-O-EZ and ingenol can relieve hepatic and gastrointestinal injuries, reduce ascites volumes, enhance the H22 cells apoptosis, ameliorate abnormal pro-inflammatory cytokines and RAAS levels, and down-regulate the expression of AQP8, AQP2, V2R. The involved metabolic pathways mainly included glycerophospholipid metabolism and arachidonic acid metabolism. And the decreasing rate of 3-O-EZ in VEK was 19.14%, the increasing rate of ingenol in VEK was 92.31%. CONCLUSION: 3-O-EZ and ingenol possess significant effect in treating MA effusion, while ingenol has lower toxicity compared with 3-O-EZ. And provide evidence for the mechanism of attenuation in toxicity without compromising the pharmacological effects of VEK. PMID: 33098970 [PubMed - as supplied by publisher]

In silico methods for metabolomic and toxicity prediction of zearalenone, α-zearalenone and β-zearalenone. Food Chem Toxicol. 2020 Oct 21;:111818 Authors: Agahi F, Juan C, Font G, Juan-García A Abstract Zearalenone (ZEA), α-zearalenol (α-ZEL) and β-zearalenol (β-ZEL) (ZEA´s metabolites) are co/present in cereals, fruits or their products. All three with other compounds, constitute a cocktail-mixture that consumers (and also animals) are exposed and never entirely evaluated, nor in vitro nor in vivo. Effect of ZEA has been correlated to endocrine disruptor alterations as well as its metabolites (α-ZEL and β-ZEL); however, toxic effects associated to metabolites generated once ingested are unknown and difficult to study. The present study defines the metabolomics profile of all three mycotoxins (ZEA, α-ZEL and β-ZEL) and explores the prediction of their toxic effects proposing an in silico workflow by using three programs of predictions: MetaTox, SwissADME and PASS online. Metabolomic profile was also defined and toxic effect evaluated for all metabolite products from Phase I and II reaction (a total of 15 compounds). Results revealed that products describing metabolomics profile were: from O-glucuronidation (1z and 2z for ZEA and 1ab, 2ab and 3ab for ZEA´s metabolites), S-sulfation (3z and 4z for ZEA and 4ab, 5ab and 6ab for ZEA´s metabolites) and hydrolysis (5z and 7ab for ZEA´s metabolites, respectively). Lipinsky´s rule-of-five was followed by all compounds except those coming from O-glucuronidation (HBA>10). Metabolite products had better properties to reach blood brain barrier than initial mycotoxins. According to Pa values (probability of activation) order of toxic effects studied was carcinogenicity > nephrotoxic > hepatotoxic > endocrine disruptor > mutagenic (AMES TEST) > genotoxic. Prediction of inhibition, induction and substrate function on different isoforms of Cytochrome P450 (CYP1A1, CYP1A2, CYP2C9 and CYP3A4) varied for each compounds analyzed; similarly, for activation of caspases 3 and 8. Relying to our findings, the metabolomics profile of ZEA, α-ZEL and β-ZEL analyzed by in silico programs predicts alteration of systems/pathways/mechanisms that ends up causing several toxic effects, giving an excellent sight and direct studies before starting in vitro or in vivo assays contributing to 3Rs principle; however, confirmation can be only demonstrated by performing those assays. PMID: 33098936 [PubMed - as supplied by publisher]

Liraglutide treatment and acylcarnitine profiles in Egyptian obese insulin-resistant females. Eur J Pharmacol. 2020 Oct 21;:173668 Authors: Hussein NA, Ebied SA, Nour HA, Zaki UK, El-Kotishy SM, Salem TM Abstract Using metabolomics technique to investigate the response to liraglutide treatment produces helpful information regarding the effects of drug on metabolic regulation. This study tested whether loss of weight by liraglutide combined with decreasing acylcarnitines (AcylCNs) represent an effective strategy to improve insulin sensitivity in obese insulin-resistant females. AcylCN profiles by tandem mass spectrometry, plasma glycosylated hemoglobin, lactate, pyruvate, serum fasting glucose, creatinine, and insulin were assessed for obese insulin-resistant females before and after treatment with liraglutide for 3 months and non-obese females. All studied parameters in obese insulin-resistant females before treatment were significantly higher than control subjects except C0 and C3 levels which were significantly low. Liraglutide treatment was effective in weight loss, increased C0 and C3 levels and decreased values of all other studied parameters comparing with before treatment but still higher than control. However, creatinine level was unaffected by treatment. This study can conclude that circulating AcylCN profiles can reflect mitochondrial overload that happen in response to obesity. Also, AcylCNs can be used as markers for diagnosis of metabolic disorders. Liraglutide treatment leads to durable improvements in weight reduction and glycometabolic control and the utilization of intracellular glucose. PMID: 33098833 [PubMed - as supplied by publisher]

Pulmonary fibrosis alters gut microbiota and associated metabolites in mice: An integrated 16S and metabolomics analysis. Life Sci. 2020 Oct 21;:118616 Authors: Gong GC, Song SR, Su J Abstract AIMS: The "gut-lung axis" reflects intimate connection and bidirectional effect between gut and lung, involving numerous lung diseases. Pulmonary fibrosis is a progressive interstitial lung disease with high fatality rate, so far, its association with gut remains unexplored. We investigated the correlation between pulmonary fibrosis and gut microbiota. MATERIALS AND METHODS: We collected feces from two pulmonary fibrotic models respectively, and performed a combinatory study using 16S rDNA sequencing and non-targeted metabonomics. Correlation matrix was used to indicate the correlation between microbiome, metabolites and fibrotic indicators, and the possibility of gut microbiota in identifying pulmonary fibrosis was assessed by ROC analysis. KEY FINDINGS: 412 genera of microflora and 26 kinds of metabolites were synchronously altered with same trend in two models but differed observably with control. Among these, 7 microorganisms and 9 metabolites were the typical representatives, which were correlated significantly and highly correlated with fibrotic indicators shown by correlation matrix. ROC analysis indicated that it was dependable to identify pulmonary fibrosis by using gut microorganisms and metabolites in both models (AUC > 0.85, p < 0.01). SIGNIFICANCE: In summary, our findings first revealed a previously unknown correlation between gut and pulmonary fibrosis in mouse models, which creates novel insights of the interaction between pulmonary fibrosis and gut microbiota. PMID: 33098825 [PubMed - as supplied by publisher]

Caloric restriction mimetics for the treatment of cardiovascular diseases. Cardiovasc Res. 2020 Oct 24;: Authors: Sciarretta S, Forte M, Castoldi F, Frati G, Versaci F, Sadoshima J, Kroemer G, Maiuri MC Abstract Caloric restriction mimetics (CRMs) are emerging as potential therapeutic agents for the treatment of cardiovascular diseases. CRMs include natural and synthetic compounds able to inhibit protein acetyltransferases, to interfere with acetyl coenzyme A biosynthesis or to activate (de)acetyltransferase proteins. These modifications mimic the effects of caloric restriction, which is associated with the activation of autophagy. Previous evidence demonstrated the ability of CRMs to ameliorate cardiac function and reduce cardiac hypertrophy and maladaptive remodeling in animal models of aging, mechanical overload, chronic myocardial ischemia, as well as in genetic and metabolic cardiomyopathies. In addition, CRMs were found to reduce acute ischemia-reperfusion injury. In many cases, these beneficial effects of CRMs appeared to be mediated by autophagy activation. In the present review, we discuss the relevant literature about the role of different CRMs in animal models of cardiac diseases, emphasizing the molecular mechanisms underlying the beneficial effects of these compounds and their potential future clinical application. PMID: 33098415 [PubMed - as supplied by publisher]

Salted and Unsalted Zhàcài (Brassica juncea var. tumida) Alleviated High-Fat Diet-Induced Dyslipidemia by Regulating Gut Microbiota: A Multiomics Study. Mol Nutr Food Res. 2020 Oct 23;:e2000798 Authors: Li W, Chen C, Chen M, Zhang X, Ji Q, Wang Y, Zheng Q, Tan S, Gao X, Lu Y Abstract SCOPE: Zhàcài, a salting-processed Brassica juncea var. tumida vegetable, is widely consumed as a pickle, but little is known about the health benefits of both salted and unsalted Zhàcài as a whole food. METHODS AND RESULTS: The preventive effects of salted and unsalted Zhàcài against dyslipidemia wereassessed in high-fat diet (HF)-fed mice. HF intake for 12 continuous weeks caused dyslipidemia in mice, as evidenced by the elevations in serum total triglyceride, total cholesterol and low-density lipoprotein cholesterol levels by 30%, 66% and 117%, respectively. Metabolomics analysis and the 16S rRNA genes sequencing suggested that dietary administration of salted and unsalted Zhàcài (2.5% w/w) alleviates HF-induced dyslipidemia, metabolic disorders of short-chain fatty acids, and disturbance of intestinal flora in mice. These positive effects of unsalted Zhàcài werestronger than those of salted Zhàcài. Moreover, fecal bacteria transplantation confirmed the antidyslipidemia of Zhàcài. CONCLUSION: These results suggest that consumption of Zhàcài may prevent HF-induced dyslipidemia by regulating gut microbiota. This article is protected by copyright. All rights reserved. PMID: 33098239 [PubMed - as supplied by publisher]

Heat stress alters serum lipid metabolism of Chinese indigenous broiler chickens-a lipidomics study. Environ Sci Pollut Res Int. 2020 Oct 24;: Authors: Guo Y, Balasubramanian B, Zhao ZH, Liu WC Abstract Heat stress (HS) by high-temperature environment reduced the production performance of poultry and caused losses to the breeding industry. The present study was conducted to investigate the effects of HS on serum lipidomics in Chinese indigenous slow-growing broiler chickens (Huaixiang chickens). A total of 40 8-week-old female Huaixiang chickens were randomly allocated to two groups, including normal temperature (NT, fed basal diet) and HS (fed basal diet), and each group consisted of five replicates with four birds per replicate. NT and HS groups were exposed to 21.3 ± 1.2 °C and 32.5 ± 1.4 °C for 4 weeks, respectively. Serum lipidomics in broilers was determined by liquid chromatography-mass spectrometry (LC-MS)-based metabolomics. The results indicated that there were significant differences in metabolic spectra between the groups, and a total of 17 differential metabolites were screened. Compared with NT group, HS group reduced the serum ceramide (cer) (d18:1/22:0), cer (d18:1/24:1), cer (d20:2/22:2), lyso-phosphatidylcholine (LPC) (18:0), phosphatidylcholine (PC) (18:0/20:4), PC (15:0/23:4), PC (18:0/22:6), PC (18:2/18:2), phosphatidylethanolamine (PE) (18:1/18:1), polyethylene terephthalate (PEt) (37:3/8:0), phosphatidylglycerol (PG) (32:1/16:2), phosphatidyl methyl ethanolamine (PMe) (19:3/13:0), PMe (26:1/9:0), sphingomyelin (SM) (d16:0/18:1), triglycerides (TG) (18:0/18:1/18:2), and TG (19:4/21:6/21:6) levels [variable importance in the projection (VIP > 1 and P < 0.05)], while HS group increased serum PC (17:0/17:0) content (VIP > 1 and P < 0.05). Also, metabolic pathway analysis showed that the pathways of glycerolphospholipid, linoleic acid and α-linolenic acid metabolism, and glycosylphosphatidylinositol (GPI)-anchored biosynthesis were changed (P < 0.05). In conclusion, HS led to the disorders of serum lipid metabolism in broilers, and mainly downregulated serum content of phospholipids. These findings provide novel insights into the effects of HS on serum lipidomics in indigenous slow-growing chickens. PMID: 33098000 [PubMed - as supplied by publisher]

Ruminal degradation of rumen-protected glucose influences ruminal microbiota and metabolites in early lactation dairy cows. Appl Environ Microbiol. 2020 Oct 23;: Authors: Wang Y, Nan X, Zhao Y, Wang Y, Jiang L, Xiong B Abstract Rumen-protected glucose (RPG) plays an important role in alleviating the negative energy balance of dairy cows. This study used a combination of rumen microbes 16S and metabolomics to elucidate the changes of rumen microbial composition and rumen metabolites of different doses of RPG's rumen degradation part in early lactation dairy cows. Twenty-four multiparous Holstein cows in early lactation were randomly allocated to control (CON), low RPG (LRPG), medium RPG (MRPG) or high RPG (HRPG) groups in a randomized block design. The cows were fed a basal total mixed ration diet with 0, 200, 350 and 500 g RPG per cow per day, respectively. Rumen fluid samples were analyzed using Illumina MiSeq sequencing and ultrahigh-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. MRPG supplementation increased bacterial richness and diversity, including increasing the relative abundance of cellulolytic bacteria, such as Ruminococcus, Lachnospiraceae_NK3A20_group, Ruminiclostridium, and Lachnospiraceae_UCG-008 MRPG significantly increased the concentrations of acetate, propionate, butyrate, and total volatile fatty acid in the rumen. Ruminal fluid metabolomics analysis showed that RPG supplementation could significantly regulate the synthesis of amino acids digested by protozoa in the rumen. Correlation analysis of ruminal microbiome and metabolome revealed some potential relationships between major bacteria abundance and metabolites concentrations. Our analysis found that RPG supplementation of different doses can change the diversity of microorganisms in the rumen and affect the rumen fermentation pattern and microbial metabolism, and a daily supplement of 350 g RPG might be the ideal dose.IMPORTANCE Dairy cows in early lactation are prone to negative energy balance because their dry matter intake cannot meet the energy requirements of lactation. Rumen-protected glucose is used as an effective feed additive to alleviate the negative energy balance of dairy cows in early lactation. But one thing that is overlooked is that people often think that rumen-protected glucose is not degraded in the rumen, thus ignoring its impact on the microorganisms in the rumen environment. Our investigation and previous experiments have found that rumen-protected glucose is partially degraded in the rumen. However, there are few reports on this part of the research. Therefore, we conducted research on this problem and found that 350g/d rumen-protected glucose supplementation can promote the development and metabolism of rumen flora. This provides a theoretical basis for the extensive application of rumen bypass glucose in the later stage. PMID: 33097510 [PubMed - as supplied by publisher]

Analysis of secondary metabolites induced by yellowing process for understanding rice yellowing mechanism. Food Chem. 2020 Sep 28;:128204 Authors: Liu Y, Liu J, Wang R, Sun H, Li M, Strappe P, Zhou Z Abstract The current study applied wide-targeted metabolomics based approach using LC-ESI-MS/MS to characterize the secondary metabolic difference between yellowed and normal rice. The results indicated that the biosynthesis of secondary metabolites including flavonoids, flavonols and phenolic acids was significantly enhanced during the rice yellowing process, which appears to be highly managed by phenylpropanoid metabolism and flavonoid biosynthetic pathways. Furthermore, rice yellowing led to an increased color parameter b* value, and a number of increased secondary metabolites in the yellowed rice such as homoeriodictyol, naringenin chalcone, 4,2',4',6'-tetrahydroxychalcone contributed to the yellow color. These may have application as potential biomarkers for characterizing rice yellowing. PMID: 33097330 [PubMed - as supplied by publisher]

Engineering cofactor metabolism for improved protein and glucoamylase production in Aspergillus niger. Microb Cell Fact. 2020 Oct 23;19(1):198 Authors: Sui YF, Schütze T, Ouyang LM, Lu H, Liu P, Xiao X, Qi J, Zhuang YP, Meyer V Abstract BACKGROUND: Nicotinamide adenine dinucleotide phosphate (NADPH) is an important cofactor ensuring intracellular redox balance, anabolism and cell growth in all living systems. Our recent multi-omics analyses of glucoamylase (GlaA) biosynthesis in the filamentous fungal cell factory Aspergillus niger indicated that low availability of NADPH might be a limiting factor for GlaA overproduction. RESULTS: We thus employed the Design-Build-Test-Learn cycle for metabolic engineering to identify and prioritize effective cofactor engineering strategies for GlaA overproduction. Based on available metabolomics and 13C metabolic flux analysis data, we individually overexpressed seven predicted genes encoding NADPH generation enzymes under the control of the Tet-on gene switch in two A. niger recipient strains, one carrying a single and one carrying seven glaA gene copies, respectively, to test their individual effects on GlaA and total protein overproduction. Both strains were selected to understand if a strong pull towards glaA biosynthesis (seven gene copies) mandates a higher NADPH supply compared to the native condition (one gene copy). Detailed analysis of all 14 strains cultivated in shake flask cultures uncovered that overexpression of the gsdA gene (glucose 6-phosphate dehydrogenase), gndA gene (6-phosphogluconate dehydrogenase) and maeA gene (NADP-dependent malic enzyme) supported GlaA production on a subtle (10%) but significant level in the background strain carrying seven glaA gene copies. We thus performed maltose-limited chemostat cultures combining metabolome analysis for these three isolates to characterize metabolic-level fluctuations caused by cofactor engineering. In these cultures, overexpression of either the gndA or maeA gene increased the intracellular NADPH pool by 45% and 66%, and the yield of GlaA by 65% and 30%, respectively. In contrast, overexpression of the gsdA gene had a negative effect on both total protein and glucoamylase production. CONCLUSIONS: This data suggests for the first time that increased NADPH availability can indeed underpin protein and especially GlaA production in strains where a strong pull towards GlaA biosynthesis exists. This data also indicates that the highest impact on GlaA production can be engineered on a genetic level by increasing the flux through the pentose phosphate pathway (gndA gene) followed by engineering the flux through the reverse TCA cycle (maeA gene). We thus propose that NADPH cofactor engineering is indeed a valid strategy for metabolic engineering of A. niger to improve GlaA production, a strategy which is certainly also applicable to the rational design of other microbial cell factories. PMID: 33097040 [PubMed - as supplied by publisher]