De novo transcriptome assembly and metabolomic analysis of three tissue types in Cinnamomum cassia / 中草药·英文版

OBJECTIVE@#The barks, leaves, and branches of Cinnamomum cassia have been historically used as a traditional Chinese medicine, spice, and food preservative, in which phenylpropanoids are responsible compounds. However phenylpropanoid biosynthesis pathways are not clear in C. cassia. We elucidated the pathways by descriptive analyses of differentially expressed genes related to phenylpropanoid biosynthesis as well as to identify various phenylpropanoid metabolites.@*METHODS@#Chemical analysis, metabolome sequencing, and transcriptome sequencing were performed to investigate the molecular mechanisms underlying the difference of active components content in the barks, branches and leaves of C. cassia.@*RESULTS@#Metabolomic analysis revealed that small amounts of flavonoids, coumarine, and cinnamaldehyde accumulated in both leaves and branches. Transcriptome analysis showed that genes associated with phenylpropanoid and flavonoid biosynthesis were downregulated in the leaves and branches relative to the barks. The observed differences in essential oil content among the three tissues may be attributable to the differential expression of genes involved in the phenylpropanoid and flavonoid metabolic pathways.@*CONCLUSION@#This study identified the key genes in the phenylpropanoid pathway controling the flavonoid, coumarine, and cinnamaldehyde contents in the barks, branches and leaves by comparing the transcriptome and metabolome. These findings may be valuable in assessing phenylpropanoid and flavonoid metabolites and identifying specific candidate genes that are related to the synthesis of phenylpropanoids and flavonoids in C. cassia.

Targeted metabolomic analysis of phenylpropanoid metabolites in Astragalus membranaceus var. mongholicus in response to Fusarium solani infection / 药学学报

Root rot severely restricts the sustainable development of Astragalus membranaceus var. mongholicus (AMM) industry. Resistance breeding is an economical and environmentally safe way to manage the disease and its key lies in the obtaining of resistance indicators. This study aimed to quickly and accurately screen the resistance-related (RR) metabolites so as to provide reference for the screening of indicators of AMM breeding for resistance. LC-MS-based targeted metabolomics and real-time quantitative PCR technology were employed, in combination with multivariate statistical analysis, in analyzing the dynamic changes of phenylpropanoid metabolites in AMM in response to root rot pathogen Fusarium solani (FS) infection and identifying the differential metabolites. The LC-MS method established showed high sensitivity; each metabolite had a good linear relationship (R2 ≥ 0.968 9) in the corresponding linear range of the respective standard curve; the recoveries and the relative standard deviations (RSDs) (n = 6) ranged from 70% to 107% and from 1.2% to 9.9%, respectively. Obvious disturbances were observed in the changes of the targeted metabolites in AMM infected by FS. These metabolites, compared with the mock-inoculated (CK) group, showed different up or down regulation with time series. Calycosin-7-O-β-D-glucoside, ononin, calycosin and formononetin were identified as differential metabolites, and they all belong to flavonoids. The first three compounds were significantly negatively correlated (r ≤ -0.97, P < 0.05) with the content of FS in the root of AMM. As potential RR metabolites, they are helpful in obtaining promising resistance indicators for AMM against FS infection.

Advances in metabolomics of cholangiocarcinoma / 药学实践杂志

As a highly malignant tumor, the diagnosis of cholangiocarcinoma (CCA) is often late and the prognosis is poor for which the early symptoms are atypical and the lack of accurate biomarkers. Metabolomics is an emerging science that researches the alterations of all endogenous small molecule metabolites in an organism under the influence of pathological, physiological or genetic modification. The development and progress of CCA is closely related to metabolism. Metabolomic is characterized by global analysis, high throughput and reflects real-time alterations in biology system, providing a new avenue for biomarker screening and diseases diagnosis and treatment. The advances of metabolomics studies on CCA in the recent years were reviewed in this paper which could provide the reference for further research.

Liujunzi decoction ameliorats cisplatin-induced anorexia via adjusting metabolic disorders in rats / 中国药理学与毒理学杂志

OBJECTIVE Cisplatin is a formidable chemotherapy agent widely applying in antineoplastic treatments, but its side effects often limit the clinical usage. Metabolic disorders are one of the side effects induced by cisplatin, which closely relate to the onset of chemotherapy-induced anorexia (CIA) in cancer patients but lacks effective controls. Liujunzi decoction (LJZD) is a traditional Chinese formula that has a promising effect in treating CIA. However, whether LJZD ameliorates CIA through adjusting cisplatin-induced metabolic disorders remain unknow. The present study evalu?ated the mechanism of cisplatin-induced metabolic disorders, and the effect of LJZD in ameliorating these disturbances. METHODS 42 male Sprague-Dawley (SD) rats (180-220 g) were randomly divided into 3 groups:normal control group (distilled water+saline), model group (distilled water+cisplatin), LJZD group (4.8 g·kg-1 Liujunzi decoction ingredients+cisplatin). Intragastrical administered each drug twice a day (7:00-19:00) since day 0 for 4 d, animals were intraperito?neal injected with cisplatin 6 mg·kg-11 h after administration while normal control groups were injected with same volume of saline. On day 3, each group was anesthetized with pentobarbital sodium 45 mg · kg-1 (ip), and blood samples were collected from aorta abdominalis. Then the samples were analyzed using an LC-ESI-MS/MS system. Significantly regu?lated metabolites between groups were determined by VIP≥1 and absolute Log2FC (fold change)≥1. Identified metabo?lites were mapped to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database using Metaboanalyst 5.0 (https://www.metaboanalyst.ca/). RESULTS A total of 133, 77 and 32 differential metabolites were filtrated in control vs model, control vs LJZD and model vs LJZD groups respectively. Comparing to control, the levels of hexadecanoic acid (Log2FC=6.3153), linoleic acid (Log2FC=5.3478), and 8, 11-icosadienoic acid (Log2FC=5.2342) significantly increased, and the levels of N-acetyl-L-tyrosine (Log2FC = -2.6283), cinnamic acid (Log2FC = -2.3381), N-acetylphenylalanine (Log2FC = -2.2501) significantly decreased in model group. The KEGG pathway enrichments of these metabolites indi?cated that, cisplatin-induced metabolic disorders by disturbing metabolism pathways such as linoleic acid metabolism, biosynthesis of unsaturated fatty acids, and phenylalanine metabolism, which suggested that the onset of CIA was partly associated with the metabolic disorders of linoleic acid, unsaturated fatty acids, and phenylalanine. Compared to control, treatment of LJZD significantly increased the levels of 4-hydroxytryptamine (Log2FC =12.0186), hexadecanoic acid (Log2FC = 5.7412), linoleic acid (Log2FC = 5.1877) and significantly decreased the levels of N-acetylmethionine (Log2FC=-1.7317), 2-aminoethanesulfinic acid (Log2FC=-1.6578), N-acetyl-L-tyrosine (Log2FC=-1.5355). And com?paring to the model group, 4-hydroxytryptamine (Log2FC = 12.0186), 7, 12-diketocholic acid (Log2FC = 2.0998), N-acetylneuraminic acid (Log2FC = 2.0560) markedly increased, and 3-hydroxy-3-methylpentane-1 (Log2FC = -1.9202), 5-dioic acid (Log2FC = -1.7166), N-isovaleroylglycine, hexanoyl glycine (Log2FC = -1.4958) markedly decreased in LJZD group. It was worth noting that, there were 23 differential metabolites filtrated both in control vs model and model vs LJZD groups, which were the key metabolites of LJZD in treating CIA. Among these 23 common metabolites, there were 16 metabolites excluding the control vs LJZD group, that was, LJZD had no effect in normal rats while being able to ameliorated cisplatin-induced metabolic disorders by regulating these 16 metabolites. Cisplatin-induced downregula?tion of 11 metabolites such as hydrocinnamic acid, (±)12(13)epoxy-9Z-octadecenoic acid, cinnamic acid were upregulated after LJZD treatment, and cisplatin-induced upregulation of imidazoleacetic acid, 2'-deoxycytidine-5'-monophosphate and other 5 metabolites were downregulated by LJZD. The KEGG pathway analysis indicated that the linoleic acid metabolism, histidine metabolism, and pyrimidine metabolism were the most enriched metabolic pathway. Thus, cisplatin-induced metabolic disturbances mainly by disturbing linoleic acid metabolism, histidine metabolism, and pyrimidine metabolism, and LJZD interacted with these metabolic pathways to reduce metabolic disorders and thus ameliorated CIA. CONCLUSION Cisplatin-induced anorexia was closely related to the metabolic disorders of linoleic acid metabo?lism, biosynthesis of unsaturated fatty acids, and phenylalanine metabolism. The mechanism of LJZD in ameliorating CIA was in concerned with the metabolic adjustments, relating to the regulation of linoleic acid metabolism, histidine metabolism, and pyrimidine metabolism.

Untargeted Metabolomic Profiling of Liver and Serum in Mouse during Normal Aging / 中国医学科学院学报

Objective To obtain the metabolome profiles in liver and serum of mice during normal aging. Methods The liver and serum samples of ten 2-month-old mice and ten 18-month-old C57BL/6J mice under physiological conditions were collected.Metabolites were identified and quantified by liquid chromatography-tandem mass spectrometry.The overall assessment,differential screening,and functional analysis were performed with the filtered high-quality data. Results In the negative-ion mode and positive-ion mode,242 and 399 metabolites were identified in the liver and 265 and 230 in serum,respectively.The difference of metabolome between young and old mice was moderate.The upregulated metabolites identified in aging liver were related to the metabolism of riboflavin,glucose,and arachidonic acid,while the downregulated ones were associated with the metabolism of pyrimidine,purine,glycerophospholipid,glutathione,and nicotinamide.Altered metabolites in serum during aging were involved in a variety of nucleic acid metabolism-related pathways,such as pyrimidine metabolism,purine metabolism,one carbon pool by folate,and amino sugar and nucleotide sugar metabolism. Conclusions The metabolome profiles of mouse liver and serum both revealed dysregulated nucleic acid metabolism pathways during normal aging.This study provides metabolome data for further research on aging-associated mechanism and may support the discovery of intervention methods for aging.

Metabolic mechanism of Prunella vulgaris in treatment of ethanol-induced oxidative stress in rats based on metabonomics / 中国中药杂志

Prunella vulgaris(PV) is an edible and traditional medicinal herb which has a wide range application in fighting inflammation and oxidative stress, and protecting liver. Now it has been used to treat various types of liver diseases and has significant clinical efficacy. This study aims to investigate the effects of PV on ethanol-induced oxidative stress injury in rats and its metabolic mechanism. The rats were divided into control group, model group, PV group, and VC group. The liver protection of PV was identified by measuring pharmacological indexes such as antioxidant and anti-inflammatory activity. The metabolic mechanism of long-term ethanol exposure and the metabolic regulation mechanism of PV treatment were studied by LS-MS metabonomics. The pharmacological investigation indicated that ethanol could significantly decrease the contents of SOD, GSH-Px, CAT and other antioxidant enzymes in liver and increase the content of MDA. At the same time, PV could significantly reduce the contents of inflammatory factors(TNF-α, IL-6 and IL-1β) and liver function markers(ALT, AST, ALP) in serum. What's more, long-term ethanol exposure could significantly cause liver injury, while PV could protect liver. Metabolomics based on multiple statistical analyses showed that long-term ethanol exposure could cause significant metabolic disorder, and fatty acids, phospholipids, carnitines and sterols were the main biomarkers. Meanwhile, pathway analysis and enrichment analysis showed that the β oxidation of branched fatty acids was the main influencing pathway. Also, PV could improve metabolic disorder of liver injury induced by ethanol, and amino acids, fatty acids, and phospholi-pids were the main biomarkers in PV treatment. Metabolic pathway analysis showed that PV mainly regulated metabolic disorder of ethanol-induced liver injury through phenylalanine, tyrosine and tryptophan biosynthetic pathways. This study could provide a new perspective on the hepatoprotective effect of natural medicines, such as PV.

Metabolomic study of Gardenia jasminoside var. radicans and geniposide on degranulation model of RBL-2H3 cells / 中草药

Objective: To study the intervention effect of Gardenia jasminoside var. radicans and its main effective component of geniposide on the degranulation model of RBL-2H3 cells based on metabolomics. Methods: The changed metabolite profile of RBL-2H3 cells was detected by UPLC-QTOF-MS; PCA (principal component analysis) and OPLS-DA (orthogonal partial least squares discriminant analysis) in SIMCA software were used to select the potential biomarkers. Meanwhile, the clustering and heat map analysis for those potential biomarker levels were carried out by MEV software. Result: A total of 54 and 46 relevant biomarkers of G. jasminoside var. radicans and geniposide were selected, of which 31 biomarkers enriched in five disturbed metabolite pathways, including glycine, aspartic acid and glutamate metabolism, glutathione metabolism, histamine metabolism, energy metabolism, and nicotinamide metabolism pathways. Conclusion: G. jasminoside var. radicans and geniposide exerts the inhibitory effect on the degranulation model of RBL-2H3 cells by regulating histamine metabolism, oxidative stress and energy metabolism, and geniposide was one of the main efficacious substance basis of G. jasminoside var. radicans.

Association between depression and metabolomic biomarkers of patients with amyotrophic lateral sclerosis / 西安交通大学学报(医学版)

Objective: To investigate the association between the incidence of depression and the levels of metabolomic indexes of patients with amyotrophic lateral sclerosis (ALS). Methods: We recruited 206 ALS patients admitted to The First Affiliated Hospital of Xi'an Jiaotong University between November 2013 and November 2018 using Hamilton Rating Scale for Depression (HRSD-17) to evaluate the degree of depression. Meanwhile, we also collected body mass index (BMI), creatinine, uric acid, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and other metabolic indexes of these patients. Correlation analysis and regression analysis were preformed between depression score and the metabolic indexes. Results: Univariate analysis showed that the proportion of women was higher in the depression group than in the non-depression group (55.2% vs. 35.4%, P=0.005). In the depression group, BMI (21.36±2.70 vs. 22.86±3.16, P=0.001), creatinine (47.04±10.26 vs. 52.18±10.70, P=0.001), uric acid (279.39±70.30 vs. 308.49±81.37, P=0.008), and triglyceride (4.12±0.76 vs. 4.38±0.83, P=0.024) were lower than those in the non-depression group. Spearman rank correlation analysis showed that depression score was negatively correlated with BMI (rs=-0.172, P=0.013), creatinine (rs=-0.241, P<0.001), uric acid (rs=-0.224, P=0.004), and total cholesterol (rs=-0.201, P=0.002). Multivariate Logistic regression analysis showed that female [OR=2.585, CI (1.400, 4.774), P=0.002], BMI [OR=0.853, CI (0.769, 0.947), P=0.003] and triglyceride [OR=0.669, CI (0.449, 0.999), P=0.049] were negatively correlated with depression in ALS patients. Further analysis showed that when BMI was low, the proportion of patients with depression increased significantly. Conclusion: Factors such as low BMI, low triglyceride and female may increase the risk of depression in ALS patients. More attention should be paid to these factors in clinical work and reasonable intervention should be given timely.

Interventional effects of Zushima Tablets on lipid metabolomic disorder of rheumatoid arthritis in rats based on UPLC-Q-Exactive Orbitrap MS / 中草药

Objective To explore the changed trend of endogenous lipid metabolites in rats with rheumatoid arthritis during different disease periods and the regulation of Zushima Tablets on differential metabolites based on UPLC-Q-Exactive Orbitrap MS. Methods The collagen-induced arthritis (CIA) rats were established using bovine type II collagen. The serum samples were collected before (0 d) and 14, 21, and 36 d after model construction from control, model, and Zushima Tablets groups [0.6 g/(kg•d)], respectively. The lipids were extracted and identified by bioinformatics analysis to find the lipid differential metabolites. Results It was obviously observed that lipid metabolism disordered in CIA rats compared with the control group. The content of three acylcarnitines was increased significantly while the level of TG showed a downward trend in the CIA model group when the TG carbon chain was shorter than 58 carbon atoms. To the opposite, the content of TG substances with atomic number greater than fifty-eight in the model group was significantly higher than that of the control group. Zushima tablet obviously regulated the metabolism levels of a phosphatidylserine, a ceramide, two acylcarnitines, four phosphatidylcholines, and four triglycerides. Conclusion This study demonstrated that rheumatoid arthritis caused the disorder of lipid metabolism while Zushima Tablets had regulatory effects on some lipid metabolites.

Metabolomic analysis of healthy human urine following administration of glimepiride using a liquid chromatography-tandem mass spectrometry

Glimepiride, a third generation sulfonylurea, is an antihyperglycemic agent widely used to treat type 2 diabetes mellitus. In this study, an untargeted urinary metabolomic analysis was performed to identify endogenous metabolites affected by glimepiride administration. Urine samples of twelve healthy male volunteers were collected before and after administration of 2 mg glimepiride. These samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and then subjected to multivariate data analysis including principal component analysis and orthogonal partial least squares discriminant analysis. Through this metabolomic profiling, we identified several endogenous metabolites such as adenosine 3′, 5′-cyclic monophosphate (cAMP), quercetin, tyramine, and urocanic acid, which exhibit significant metabolomic changes between pre- and posturine samples. Among these, cAMP, which is known to be related to insulin secretion, was the most significantly altered metabolite following glimepiride administration. In addition, the pathway analysis showed that purine, tyrosine, and histidine metabolism was affected by pharmacological responses to glimepiride. Together, the results suggest that the pharmacometabolomic approach, based on LC-MS/MS, is useful in understanding the alterations in biochemical pathways associated with glimepiride action.

Distinguishing Tendon and Ligament Fibroblasts Based on ¹H Nuclear Magnetic Resonance Spectroscopy

Tendon and ligament (T/L) have been known to be obviously different from each other in tissue level. However, due to the overlapping gene markers, distinction in cellular level has not been clearly verified yet. Recently, the use of nuclear magnetic resonance (NMR) spectroscopy has shown the potential to detect biological markers in cellular level. Therefore, in this study we applied a non-invasive technique based on NMR spectroscopy to establish biomarkers to distinguish between T/L fibroblasts. In addition the cellular morphologies and gene expression patterns were also investigated for comparison through optical microscopy and real-time polymerase chain reaction (PCR). No difference was observed from morphology and real-time PCR results, either as expected. However, we found clear differences in their metabolomic spectra using ¹H NMR spectroscopy. The calculated integral values of fatty acids (with chemical shifts at ~0.9, 1.26, 1.59, 2.05, 2.25, and 2.81 ppm), lactate (~1.33 ppm), and leucine (~2.72 ppm) were significantly different between the two types of fibroblasts. To be specific tendon group exhibited higher level of the metabolite than ligament group. In conclusion, in-cell metabolomic evaluation by NMR technique used in this study is believed to provide a promising tool in distinguishing cell types, especially T/L cells, which cannot be classified by conventional biological assays.

Metabolomic profiling reveals distinct patterns of tricarboxylic acid disorders in blood stasis syndrome associated with coronary heart disease / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the underlying metabolomic profifiling of coronary heart disease (CHD) with blood stasis syndrome (BSS).</p><p><b>METHODS</b>CHD model was induced by a nameroid constrictor in Chinese miniature swine. Fifteen miniature swine were randomly divided into a model group (n=9) and a control group (n=6), respectively according to arandom number table. After 4 weeks, plasma hemorheology was detected by automatic hemorheological analyzer, indices including hematocrit, plasma viscosity, blood viscosity, rigidity index and erythrocyte sedimentation rate; cardiac function was assessed by echocardiograph to detect left ventricular end-systolic diameter (LVED), left ventricular end-diastolic diameter (LVEDd), ejection fraction (EF), fractional shortening (FS) and other indicators. Gas chromatography coupled with mass spectrometry (GC-MS) and bioinformatics were applied to analyze spectra of CHD plasma with BSS.</p><p><b>RESULTS</b>The results of hemorheology analysis showed signifificant changes in viscosity, with low shear whole blood viscosity being lower and plasma viscosity higher in the model group compared with the control group. Moreover, whole blood reduction viscosity at high shear rate and whole blood reduction viscosity at low shear rate increased signifificantly (P <0.05). The echocardiograph results demonstrated that cardiac EF and FS showed signifificant difference (P <0.05), with EF values being decreased to 50% or less. The GC-MS data showed that principal component analysis can clearly separate the animals with BSS from those in the control group. The enriched Kyoto Encyclopedia of Genes and Genomes biological pathways results suggested that the patterns involved were associated with dysfunction of energy metabolism including glucose and lipid disorders, especially in glycolysis/gluconeogenesis, galactose metabolism and adenosine-triphosphate-binding cassette transporters.</p><p><b>CONCLUSIONS</b>Glucose metabolism and lipid metabolism disorders were the major contributors to the syndrome classifification of CHD with BSS.</p>

Analysis on endogenous metabolites in cecal tissue of CUMS-induced depression rats after Xiaoyao San intervention by GC-MS metabolomics / 中草药

Objective: To investigate the changes of endogenous metabolites in cecal tissue of CUMS-induced depression rat model interfered by Xiaoyao San via GC-MS metabolomics. Methods: Chronic unpredictable mild stress (CUMS) rat model was used and Xiaoyao San and fluoxetine hydrochloride (fluoxetine) treatment were intervention drug. The endogenous metabolites were analyzed and identified by NIST 05 database or authentic standards. The final data were introduced into SIMCA-P 13.0 software package for multivariate analysis. Results: The CUMS rat model was successfully duplicated, the metabolites of alanine, serine, and glutamic acid were reduced at fluoxetine group and Xiaoyao San group, and palmitic acid and stearic acid were increased in fluoxetine group in cecal tissue of rats after drug intervention, compared with model group with significant difference (P < 0.01 or 0.05). Conclusion: The endogenous metabolites were changed by Xiaoyao San intervention significantly in cecal tissue of CUMS rats, which provides a basis for further study of the mechanism of Xiaoyao San treatment of depression.

Comparison on chemical constituents between Paeoniae Alba Radix and Paeoniae Rubra Radix using NMR based metabolomic approach / 中草药

Objective: To compare the chemical constituents of Paeoniae Alba Radix and Paeoniae Rubra Radix, and to provide a basis for quality evaluation. Methods: NMR-based metabolomic approach combined with multivariate statistical analysis was used to investigate the differential metabolites between Paeoniae Alba Radix and Paeoniae Rubra Radix. Results: Thirty-two metabolites were identified in the 1H-NMR spectra, and the multivariate statistical analysis showed that Paeoniae Alba Radix and Paeoniae Rubra Radix could be separated clearly. Paeoniae Alba Radix contained more arginine, threonine, acetic acid, aspartic acid, glutamine, GABA, citric acid, succinate, lactate, albiflorin, 6-O-galloyl albiflorin, 1, 2, 3, 4, 6-pentagalloyglucose, and gallic acid, while Paeoniae Rubra Radix contained more alanine, α-glucose, sucrose, paeoniflorin, catechin, β-sitosterol, fatty acid, and paeonol. In addition, the Pearson correlations between differential metabolites of Paeoniae Alba Radix and Paeoniae Rubra Radix also showed apparent differences. Conclusion: The results reveal the chemical differences between Paeoniae Alba Radix and Paeoniae Rubra Radix in a holistic way, and provide a scientific basis for assessing the quality of Paeoniae Alba Radix and Paeoniae Rubra Radix, as well as the correlations between the chemical constituents and pharmacological efficacy.

Effect of Coptidis Rhizoma processed with ginger juice on its property based on metabonomics / 中草药

Objective: To explore the difference of hot and cold property of Coptidis Rhizoma (CR) before and after being processed with ginger juice. Methods: To feed rats for 29 d with the decoction of un-processed CR (UPCR) and ginger juice-processed CR (GPCR), the rats' blood was collected at different administration time, the data by HPLC-MS/MS analysis were processed with PCA to determine the metabolites difference between the treatment groups. Results: On the day 29, the metabolic status of endogenous substances in rats' blood showed the biggest difference between the UPCR and GPCR groups. Through checking the endogenous biomarkers of the rats in each group, the content of markers related to amino acid energy metabolism of rats in the GPCR group was higher than that in the UPCR group, indicating the energy metabolism of the GPCR was stronger than that of the UPCR, which showed the differences in cold and hot property between the two drugs. Conclusion: The results show that the differences in potency of the UPCR and GPCR can be reflected by rats' different biological effects. The results are consistent with the traditional processing theory in Chinese materia medica that the cold property of CR could be moderated to be colder by processing with assistant materials with hot property (ginger juice). The work indicates that the metabonomic method is a valuable tool in the research of processing effect on properties of Chinese medicinal substances. The results are helpful to clarify the mechanism of processing CR with ginger juice in the future.

Metabolic response to exogenous ethanol in yeast: An in vivo statistical total correlation NMR spectroscopy approach.

In vivo NMR spectroscopy, together with selectively 13C-labelled substrates and ‘statistical total correlation spectroscopy’ analysis (STOCSY), are valuable tools to collect and interpret the metabolic responses of a living organism to external stimuli. In this study, we applied this approach to evaluate the effects of increasing concentration of exogenous ethanol on the Saccharomyces cerevisiae fermentative metabolism. We show that the STOCSY analysis correctly identifies the different types of correlations among the enriched metabolites involved in the fermentation, and that these correlations are quite stable even in presence of a stressing factor such as the exogenous ethanol.

Visualization of Multivariate Metabolomic Data / 中草药·英文版

Objective Although principal components analysis profiles greatly facilitate the visualization and interpretation of the multivariate data,the quantitative concepts in both scores plot and loading plot are rather obscure.This article introduced three profiles that assisted the better understanding of metabolomic data.Methods The discriminatory profile,heat map,and statistic profile were developed to visualize the multivariate data obtained from high-throughput GC-TOF-MS analysis.Results The discriminatory profile and heat map obviously showed the discriminatory metabolites between the two groups,while the statistic profile showed the potential markers of statistic significance.Conclusion The three types of profiles greatly facilitate our understanding of the metabolomic data and the identification of the potential markers.

Network models in the study of metabolism

The systematic study of the genetic fingerprint (genomics) and the biochemistry (metabolites) that goes with a specific cellular process requires the characterization of all the small molecules that form the profile of metabolites and the associated genes. The metabolome represents the collection of all the metabolites during certain process in an organism. The transcriptome represents the gene expression profile, all the messengers RNA in a defined condition. Then to understand the whole process, the studies of metabolites must be accompanied with studies of the gene expression, hence the metabolome must be accompanied by the transcriptome, so we can identify genes and metabolites whose synthesis is induced by a specific process, an infection or stress. Studies of metabolomics generate an enormous amount of data, then they need mathematical and computational tools to establish the correlations between the biochemical and genetic data, and to build up networks that represent the complex metabolic interactions that occur in each case, using tools like Graph and Networks Theory to elucidate the emergent properties inherent to the complex interactions of the metabolic maps. This paper describes the major mathematical tools that can be used for these studies, with emphasis on a semi-qualitative proposal known as the kinetic structural model.