Objective To study the metabolic profiles in the urine samples of rats dosed with decoction of the caulis of Aristolochia manshuriensis and the relationship between the results of blood biochemical analysis and histopathological analysis,and to explore the feasibility of the application of NMR-based metabonomics to toxicology of Chinese medicine.Methods Male Wistar rats were administrated by ig 36,32,28,and 24 g/kg of A.manshuriensis or the equal volume of distilled water for 6 d,respectively.Urine were collected and their()~1H-NMR spectra were acquired,and then subjected to data process and principal component ana-(lysis)(PCA).Blood biochemical analysis and histopathological examination were carried out.Results(Compared) to control groups,the urinary concentrations of TMAO,taurine,creatinine,DMG,citrate,and DMA in dosed groups decreased,while those of acetate,alanine,and some other amino acids increased to a great extent.The dosed groups can be readily discriminated from the controls based on PCA,with acetate and TMAO as main discriminators.A good agreement was achieved within clinical chemistry,microscopically examination and PCA data.Conclusion The caulis of A.manshuriensis can induce renal lesion as revealed by the metabonomic analysis of rat urine samples as well as blood biochemical analysis and histopathological examinations.The results show that the metabonomic approach is a promising new technology in toxicology.

Metabonomics is a new member in the omics field following the development of genomics, transcriptomics and proteomics, with its research object being the collection of metabolites-metabolome, the downstream products of life. Even with the development of past decade, there are still many problems to be solved in the area of experimental techniques, data analysis and results annotation. Any xenobiotics would cause the disturbance of homeostasis of organisms, resulting in the changes of metabolites. Consequently, toxicology is one of the major application areas of metabolomics, and is the earliest one. Metabolomics has been widely used in the early toxicological screening of leads, preclinical and clinical toxicology of drugs in animals and human, as well as in surrogate models such as cell lines and zebrafish. Annotation techniques for metabolic data have also been developed. In this paper, the development of metabolomic techniques and its application in toxicology are reviewed.

Production of bioethanol using starch as raw material has become a very prominent technology. However, phytate in the raw material not only decreases ethanol production efficiency, but also increases phosphorus discharge. In this study, to decrease phytate content in an ethanol fermentationprocess, Saccharomyces cerevisiae was engineered forheterologous expression of phytase on the cell surface. The phy gene encoding phytase gene was fused with the C-terminal-half region of α-agglutinin and then inserted downstream of the secretion signal gene, to produce a yeast surface-display expression vector pMGK-AG-phy, which was then transformed into S. cerevisiae. The recombinant yeast strain, PHY, successfully displayed phytase on the surface of cells producing 6.4 U/g wet cells and its properties were further characterized. The growthrate and ethanol production of the PHY strain were faster than the parent S. cerevisiae strain in the fermentation medium by simultaneous saccharification and fermentation. Moreover, the phytate concentration decreased by 91% in dry vinasse compared to the control. In summary, we constructed recombinant S. cerevisiae strain displaying phytase on the cell surface, which could effectively reduce the content of phytate, improve the utilization value of vinasse and reduce the discharge of phosphorus. The strain reported here represents a useful novel engineering platform for developing an environment-friendly system for bioethanol production from a corn substrate.
6-Phytase ; metabolism ; Biofuels ; Ethanol ; chemistry ; Fermentation ; Industrial Microbiology ; Saccharomyces cerevisiae ; metabolism ; Starch ; chemistry ; Zea mays ; chemistry

Metabonomic approaches are believed to be one of the powerful methods for disease diagnosis and assessment of patients' conditions. However, many publications have been providing the evidences of the biases caused by many factors such as diet, physical exercises, environment and individual differences in the clinical researches. For the purpose of ensuring the comparability of metabonomic 1H NMR data from different studies, it is necessary to control those nonexperimental factors in the study design and the data analysis.
Data Interpretation, Statistical ; Humans ; Magnetic Resonance Spectroscopy ; methods ; Metabolomics ; methods ; Research Design ; standards

Objective:To establish and validate the rat model of syndrome of stagnation of liver qi,followed by a primary study on this model with 1H NMR based on metabonomics to explore the essence of syndrome of stagnation of liver qi. Methods:Twelve Wistar male rats were randomly divided into two groups(model group and control group).The rats of model group were restrained by special equipment for 21 days to get into stagnation of liver qi.The behavior,fluid consumption test and plasma CORT of rats were recorded.At 22th day,animals were sacrificed and biopsies of gastric mucosa and adrenal gland were collected for pathological check,and serum samples for 1H NMR spectroscopy.The NMR data were analyzed using principal component analysis.Results:There were abnormal behaviors,such as decrease of elusion,slackness,looser stools,and matte fur were observed among model group rats.After one week the body weight of model group was significantly lower than that of control group(P

Objective: To investigate the effects of quercetin on hepatic vein metabolic profiles in rats. Methods: Male Wistar rats were administrated orally with 40 mg/kg quercetin. Hepatic vein plasma was collected at 0 h, 0.5 h, 1 h, 2 h and 4 h respectively after administration and analyzed by 1H NMR. Results: The identifiable biochemical effects associated with quercetin dosing included decreased plasma concentration of glucose and increased plasma concentration of succinate,β-hydroxybutyrate and pyruvate. Conclusion: Quercetin changes hepatic metabolism in rats, manifested mainly as increased glucose catabolism and production of ketone bodies.

Objective To synthesize 18F-AlF-NOTA-G-TMTP1 and evaluate its potential for PET imaging on nude mice bearing high-metastatic potential hepatoma cells.Methods NOTA-G-TMTP1 was synthesized by the standard Fmoc-solid phase synthetic protocols and radiolabeled with 18F using NOTA-AlF chelation method.The nude mice models bearing low-metastatic potential HCC97L and high-metastatic potential HCCLM3 xenografts were established separately.The tumor-targeting characteristics of 18F-AlF-NOTA-G-TMTP1 were assessed by microPET/CT and biodistribution assay.Results NOTA-G-TMTP1 was labeled with 18F in one step with (25±6)％ labeling yield (n=5).The radiochemical purity of 18F-AlF-NOTA-G-TMTP1 was more than 95％ with a specific activity more than 11.1 GBq/μmol.The octanol/water partition coefficient (logP) for 18F-AlF-NOTA-G-TMTP1 was-3.166±0.022.The tumor to muscle ratios were 1.8± 0.4 and 4.7±0.2 at 35 min post injection for HCC97L and HCCLM3,respectively.The uptake of 18F-AlF-NOTA-G-TMTP1 in HCCLM3 tumor was inhibited (61.4％) by unlabeled G-TMTP1.Conclusion 18F-AlF-NOTA-G-TMTP1 has been successfully synthesized.It shows specific uptake by tumor induced by the high-metastatic potential hepatoma cells.

Objective:To investigate the effects of quercetin on metabolic profiles of portal blood plasma in rats. Method:Twenty five male Wistar rats were administered orally with 40 mg/kg bw quercetin. Portal blood was collected at 0,0.5h,1 h,2 h and 4 h after dosing respectively and analyzed by 1H NMR. The acquired data were subjected to partial least-squares discriminant analysis. Results:The identified biochemical effects associated with quercetin dosing included increased plasma concentrations of dimethyl sulfoxide,lactate,glucose,alanine,glutamate,succinate,?-hydroxybutyrate,acetone and decreased plasma concentrations of citrate and tyrosine. Conclusion:Quercetin may change the intestinal endogenous metabolism significantly in rats.

Objective To investigate the effect of geographical differences on human serum metabolic profiles .Methods A total of 169 serum samples were collected from healthy individuals from 9 provinces in China and divided into four groups according to the geographical location .The nuclear magnetic resonance ( NMR) data of these samples were segmentally inte-grated, normalized,and analyzed with multivariate statistical methods using SIMCA-P 10.0 software to investigate the differ-ence in serum metabolites between eastern and western populations or between northern and southern populations .Results There were differences in a variety of small molecule metabolites in serum between eastern and western populations or be -tween northern and southern,including glucose,lipoproteins,amino acids,ketones,creatine and choline.Conclusion The geographical differences in a variety of factors (temperature,precipitation,folk culture, living habits,etc) result in the differences in human serum metabolic profiles ,which can provide appropriate reference for epidemiological studies and nu -tritional metabonomics .

Objective To explore the effect on metabolism of glucose and lipids, potential toxicity mechanism and possible biomarker candidates by analyzing urine metabonome changes of rats after oral administration of polychlorinated biphenyl congeners( PCBs) and high fat diet alone or in combination.Methods Male SD rats were divided randomly into control group,high fat diet group, PCBs group and combination group of PCBs and high fat diet.Urine samples were collected after 6-week treatment, 1 H NMR spectra were performed and analyzed by principal component analysis ( PCA) . Results The PCA scores plot of urine 1 H NMR data showed that the combined group could be easily distinguished from the other three groups, suggesting great difference in metabolism.The loading plot of the PCA revealed significant increase in the levels of lactate, glucose, creatine, 2-hydroxy-isovaleric acid and reduction in the levels of citrate, succinate, taurine, hippurate and trimethylamine oxide ( TMAO) in the combined exposure group after six-week exposure.Conclusion The altered levels of metabolites induced by combined exposure of PCBs and high fat diet may be related to the injury to mitochondrial function, reduction of energy metabolism in tricarboxylic acid cycle (TAC).These effects possibly lead to perturbations in the metabolism of glucose, lipid and amino acids.The altered metabolites may be considered biomarker candidates of toxicity induced by exposure to PCBs and high fat diet.