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    Low advanced Glycation end product diet improves the central obesity, insulin resistance and inflammatory profiles in Iranian patients with metabolic syndrome: a randomized clinical trial. Goudarzi Razieh,Sedaghat Meghdad,Hedayati Mehdi,Hekmatdoost Azita,Sohrab Golbon Journal of diabetes and metabolic disorders The study aimed to investigate the effects of 8-weeks AGEs restricted diet on glycemic control as well as lipid profile, inflammatory and oxidative stress biomarkers and IR in overweight patients with Mets. In this randomized, controlled clinical trial 40 clients were randomly assigned to take either a low AGE (L-AGE) or a regular AGE (Reg-AGE) diet. Also, both groups were advised to follow an energy-restricted diet. At baseline and after 8-weeks of intervention, anthropometric parameters, dietary intake, plasma concentrations of malondialdehyde, carboxymethyllysine, TNF-α, hs-CRP and levels of serum glucose, lipid and insulin were assessed. AGEs restriction resulted in significant changes in mean differences levels of CML ( < 0.004), FBG ( < 0.01), HOMA-IR ( < 0.04), TNF-α (p < 0.01) and MDA ( < 0.02) in comparison to Reg-AGE. Moreover, weight ( < 0.0001) and WC ( < 0.001) significantly declined in the intervention group. Our results indicate that dAGEs restriction plus a low-calorie diet is superior to a low-calorie diet in amelioration of central obesity and IR at least partially through reduction of OS and inflammation in Mets subjects. 10.1007/s40200-020-00614-0
    New serum biomarker identification and analysis by mass spectrometry in cervical precancerous lesion and acute cervicitis in South China. Qiu Feng,Su Bingsen,Li Zhao,Chen Wenke,Cao Longbing,Chen Fu,Liu Dongdong,He Jingling,Lin Ni Cancer management and research According to the statistics of WHO/IARC, cervical cancer (CC) has become the fourth malignant cancer of female worldwide and it is one of the main causes of death of women in developing countries. Potential plasma and metabolic biomarkers for CC precancerous lesions and cervicitis were indicated by LC-MS techniques, and their underlying mechanisms and functions were analyzed. Plasma samples were selected from healthy people (control), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), CC, and post-treatment patients. All polypeptide types and sequences were detected by LC-MS/MS and the results were normalized by using Pareto-scaling. Potential metabolic biomarkers were screened by applying MetaboAnalyst 4.0 software and XCMS software, and analysis of variance and enrichment analysis were performed. Metabolic pathway analysis and functional enrichment analysis were used to further investigate the significance and pathological mechanisms of potential biomarkers. Compared with healthy people, 9 differentially expressed metabolites were screened, 4 of which were up-regulated and 5 were down-regulated. LSIL group screened 7 differentially expressed metabolites, 5 of which were up-regulated and 2 were down-regulated; CC group screened 12 differentially expressed metabolites were screened, of which 9 were up-regulated and 3 were down-regulated. Eight differentially expressed metabolites were screened in the IF group, of which 5 showed up-regulation and 3 showed down-regulation. In functional enrichment analysis, differential metabolism was found to be associated with addition and coagulation cascades. Among all potential biomarkers, 2-amino-3-methyl-1-butanol, L-carnitine, Asn Asn Gln Arg, Ala Cys Ser Trp, Soladulcidine, Ala Ile Gln Arg, 2-amino-3 -Methyl-1-butanol, L-carnitine, Asn Asn Gln Arg, Ala Cys Ser Trp, Soladulcidine, Ala Ile Gln Arg can be used as predictors of precancerous lesions at different stages of CC. Among all biomarkers, 6α-fluoro-11β1,17-dihydroxypren-4-ene-3,20-dione has higher expression in the CC and HSIL groups and lower expression in the treatment group. By applying molecular markers to assess the progression of the disease, the accuracy and specificity of the diagnosis can be improved, which has certain prospects in clinical applications. 10.2147/CMAR.S205052
    Eicosapentaenoic and docosahexaenoic acids attenuate hyperglycemia through the microbiome-gut-organs axis in db/db mice. Zhuang Pan,Li Haoyu,Jia Wei,Shou Qiyang,Zhu Ya'er,Mao Lei,Wang Wenqiao,Wu Fei,Chen Xiaoqian,Wan Xuzhi,Wu Yuqi,Liu Xiaohui,Li Yin,Zhu Fanghuan,He Lilin,Chen Jingnan,Zhang Yu,Jiao Jingjing Microbiome BACKGROUND:Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been suggested to prevent the development of metabolic disorders. However, their individual role in treating hyperglycemia and the mechanism of action regarding gut microbiome and metabolome in the context of diabetes remain unclear. RESULTS:Supplementation of DHA and EPA attenuated hyperglycemia and insulin resistance without changing body weight in db/db mice while the ameliorative effect appeared to be more pronounced for EPA. DHA/EPA supplementation reduced the abundance of the lipopolysaccharide-containing Enterobacteriaceae whereas elevated the family Coriobacteriaceae negatively correlated with glutamate level, genera Barnesiella and Clostridium XlVa associated with bile acids production, beneficial Bifidobacterium and Lactobacillus, and SCFA-producing species. The gut microbiome alterations co-occurred with the shifts in the metabolome, including glutamate, bile acids, propionic/butyric acid, and lipopolysaccharide, which subsequently relieved β cell apoptosis, suppressed hepatic gluconeogenesis, and promoted GLP-1 secretion, white adipose beiging, and insulin signaling. All these changes appeared to be more evident for EPA. Furthermore, transplantation with DHA/EPA-mediated gut microbiota mimicked the ameliorative effect of DHA/EPA on glucose homeostasis in db/db mice, together with similar changes in gut metabolites. In vitro, DHA/EPA treatment directly inhibited the growth of Escherichia coli (Family Enterobacteriaceae) while promoted Coriobacterium glomerans (Family Coriobacteriaceae), demonstrating a causal effect of DHA/EPA on featured gut microbiota. CONCLUSIONS:DHA and EPA dramatically attenuated hyperglycemia and insulin resistance in db/db mice, which was mediated by alterations in gut microbiome and metabolites linking gut to adipose, liver and pancreas. These findings shed light into the gut-organs axis as a promising target for restoring glucose homeostasis and also suggest a better therapeutic effect of EPA for treating diabetes. Video abstract. 10.1186/s40168-021-01126-6
    Effects of dietary fat on gut microbiota and faecal metabolites, and their relationship with cardiometabolic risk factors: a 6-month randomised controlled-feeding trial. Wan Yi,Wang Fenglei,Yuan Jihong,Li Jie,Jiang Dandan,Zhang Jingjing,Li Hao,Wang Ruoyi,Tang Jun,Huang Tao,Zheng Jusheng,Sinclair Andrew J,Mann Jim,Li Duo Gut OBJECTIVE:To investigate whether diets differing in fat content alter the gut microbiota and faecal metabolomic profiles, and to determine their relationship with cardiometabolic risk factors in healthy adults whose diet is in a transition from a traditional low-fat diet to a diet high in fat and reduced in carbohydrate. METHODS:In a 6-month randomised controlled-feeding trial, 217 healthy young adults (aged 18-35 years; body mass index <28 kg/m; 52% women) who completed the whole trial were included. All the foods were provided during the intervention period. The three isocaloric diets were: a lower-fat diet (fat 20% energy), a moderate-fat diet (fat 30% energy) and a higher-fat diet (fat 40% energy). The effects of the dietary interventions on the gut microbiota, faecal metabolomics and plasma inflammatory factors were investigated. RESULTS:The lower-fat diet was associated with increased α-diversity assessed by the Shannon index (p=0.03), increased abundance of (p=0.007) and (p=0.04), whereas the higher-fat diet was associated with increased (p=0.04), (p<0.001) and decreased (p=0.04). The concentration of total short-chain fatty acids was significantly decreased in the higher-fat diet group in comparison with the other groups (p<0.001). The cometabolites p-cresol and indole, known to be associated with host metabolic disorders, were decreased in the lower-fat diet group. In addition, the higher-fat diet was associated with faecal enrichment in arachidonic acid and the lipopolysaccharide biosynthesis pathway as well as elevated plasma proinflammatory factors after the intervention. CONCLUSION:Higher-fat consumption by healthy young adults whose diet is in a state of nutrition transition appeared to be associated with unfavourable changes in gut microbiota, faecal metabolomic profiles and plasma proinflammatory factors, which might confer adverse consequences for long-term health outcomes. TRIAL REGISTRATION NUMBER:NCT02355795; Results. 10.1136/gutjnl-2018-317609
    Predicting Range of Initial Warfarin Dose Based on Pharmacometabolomic and Genetic Inputs. Huang Qing,Cao Ling,Luo Nan,Qian Hanyu,Wei Meng,Xue Ling,Zhou Qiang,Zou Bingjie,Tan Li,Chu Yanan,Ma Xueping,Wang Changtian,Wu Haiwei,Zhang Lei,Sun Lei,Li Demin,Fan Xialei,Miao Liyan,Zhou Guohua Clinical pharmacology and therapeutics Anticoagulation response to warfarin during the initial stage of therapy varies among individuals. In this study, we aimed to combine pharmacometabolomic and pharmacogenetic data to predict interindividual variation in warfarin response, and, on this basis, suggest an initial daily dose range. The baseline metabolic profiles, genotypes, and clinical information of 160 patients with heart valve disease served as the variables of the function of the last international normalized ratio measured before a patient's discharge (INR ) to screen for potential biomarkers. The partial least-squares model showed that two baseline metabolites (uridine and guanosine), one single-nucleotide variation (VKORC1), and four clinical parameters (weight, creatinine level, amiodarone usage, and initial daily dose) had good predictive power for INR (R  = 0.753 for the training set, 0.643 for the test set). With these biomarkers, a machine learning algorithm (two-dimensional linear discriminant analysis-multinomial logit model) was used to predict the subgroups with extremely warfarin-sensitive or less warfarin-sensitive patients with a prediction accuracy of 91% for the training set and 90% for the test set, indicating that individual responses to warfarin could be effectively predicted. Based on this model, we have successfully designed an algorithm,"IniWarD," for predicting an effective dose range in the initial 7-day warfarin therapy. The results indicate that the daily dose range suggested by the IniWarD system is more appropriate than that of the conventional genotype-based method, and the risk of bleeding or thrombus due to warfarin could thus be avoided. 10.1002/cpt.2407
    Metabolic Characterization of Peripheral Host Responses to Drainage-Resistant Klebsiella pneumoniae Liver Abscesses by Serum 1H-NMR Spectroscopy. Chang Zhihui,Wang Hairui,Li Beibei,Liu Zhaoyu,Zheng Jiahe Frontiers in cellular and infection microbiology To explore the metabolic characterization of host responses to drainage-resistant Klebsiella pneumoniae liver abscesses (DRKPLAs) with serum 1H-nuclear magnetic resonance (NMR) spectroscopy. The hospital records of all patients with a diagnosis of a liver abscess between June 2015 and December 2016 were retrieved from an electronic hospital database. Eighty-six patients with () liver abscesses who underwent percutaneous drainage were identified. Twenty patients with confirmed DRKPLAs were studied. Moreover, we identified 20 consecutive patients with drainage-sensitive Klebsiella pneumoniae liver abscesses (DSKPLAs) as controls. Serum samples from the two groups were analyzed with 1H NMR spectroscopy. Partial least squares discriminant analysis (PLS-DA) was used to perform 1H NMR metabolic profiling. Metabolites were identified using the Human Metabolome Database, and pathway analysis was performed with MetaboAnalyst 3.0. The PLS-DA test was able to discriminate between the two groups. Five key metabolites that contributed to their discrimination were identified. Glucose, lactate, and 3-hydroxybutyrate were found to be upregulated in DRKPLAs, whereas glutamine and alanine were downregulated compared with the DSKPLAs. Pathway analysis indicated that amino acid metabolisms were significantly different between the DRKPLAs and the DSKPLAs. The D-glutamine and D-glutamate metabolisms exhibited the greatest influences. The five key metabolites identified in our study may be potential targets for guiding novel therapeutics of DRKPLAs and are worthy of additional investigation. 10.3389/fcimb.2018.00174
    Altered metabolic pathways in a transgenic mouse model suggest mechanistic role of amyloid precursor protein overexpression in Alzheimer's disease. Dejakaisaya Hattapark,Harutyunyan Anna,Kwan Patrick,Jones Nigel C Metabolomics : Official journal of the Metabolomic Society INTRODUCTION:The mechanistic role of amyloid precursor protein (APP) in Alzheimer's disease (AD) remains unclear. OBJECTIVES:Here, we aimed to identify alterations in cerebral metabolites and metabolic pathways in cortex, hippocampus and serum samples from Tg2576 mice, a widely used mouse model of AD. METHODS:Metabolomic profilings using liquid chromatography-mass spectrometry were performed and analysed with MetaboAnalyst and weighted correlation network analysis (WGCNA). RESULTS:Expressions of 11 metabolites in cortex, including hydroxyphenyllactate-linked to oxidative stress-and phosphatidylserine-lipid metabolism-were significantly different between Tg2576 and WT mice (false discovery rate < 0.05). Four metabolic pathways from cortex, including glycerophospholipid metabolism and pyrimidine metabolism, and one pathway (sulphur metabolism) from hippocampus, were significantly enriched in Tg2576 mice. Network analysis identified five pathways, including alanine, aspartate and glutamate metabolism, and mitochondria electron transport chain, that were significantly correlated with AD genotype. CONCLUSIONS:Changes in metabolite concentrations and metabolic pathways are present in the early stage of APP pathology, and may be important for AD development and progression. 10.1007/s11306-021-01793-4