Study on mechanism of combined administration of Coptidis Rhizoma and Rehmanniae Radix in treating type II diabetes mellitus / 中国中药杂志

To make a preliminary study on the mechanism of Coptidis Rhizoma(CR) and Rehmanniae Radix(RR) before and after the combined administration in treating type II diabetes mellitus. The type I diabetes animal model in rats was established by fat emulsion and intraperitoneal injection with streptozotocin, in order to compare the hpyerglycemic and hypolipidemic effects of CR, RR and their combined administration of different ratio. The urinary metabolic profiling in rats of Coptidis Rhizoma and Rehmanniae Radix before and after the combined administration was analyzed by using the gas chromatography-mass spectrometry. The differences among groups in metabolome were analyzed by the principal component analysis (PCA). The biochemical index results indicated that both CR and RR before and after the combined administration could lower high blood glucose, hypertriglyceride and high cholesterol. According to the analytical results of PCA of the rats' urine samples, the CR group was the most close to the normal group, with no significant difference in CR and RR group of different combination ratios. Twelve differentiated metabolites were identified to be related to type II diabetes. Compared with the normal group, the CR-treated group showed significant increase in seven differentiated metabolites. Among CR and RR drugs with different combination ratios, CR played a major role and thus acted as the monarch drug. Whereas RR served as the ministerial drug and assisted CR to show the efficacy. This study laid a foundation for the explanation of the combination mechanism of traditional Chinese medicines.

Recent advances in metabonomics / 中国医学科学院学报

Metabonomics (or metabolomics) aims at the comprehensive and quantitative analysis of the wide arrays of metabolites in biological samples. Metabonomics has been labeled as one of the new" -omics" joining genomics, transcriptomics, and proteomics as a science employed toward the understanding of global systems biology. It has been widely applied in many research areas including drug toxicology, biomarker discovery, functional genomics, and molecular pathology etc. The comprehensive analysis of the metabonome is particularly challenging due to the diverse chemical natures of metabolites. Metabonomics investigations require special approaches for sample preparation, data-rich analytical chemical measurements, and information mining. The outputs from a metabonomics study allow sample classification, biomarker discovery, and interpretation of the reasons for classification information. This review focuses on the currently new advances in various technical platforms of metabonomics and its applications in drug discovery and development, disease biomarker identification, plant and microbe related fields.

Assessment of therapeutic effect of losartan on diabetes mellitus with gas chromatography-based metabonomics / 中国医学科学院学报

<p><b>OBJECTIVE</b>To assess the therapeutic effect of losartan on type 2 diabetes mellitus (DM2) with gas chromatography (GC)-based metabonomics.</p><p><b>METHODS</b>DM2 patients were dosed with losartan (100 mg/d) and urines were collected at week 8 and 12. The biochemical criteria (blood pressure, urinary albumen, urinary 8-hydroxy-2'-deoxyguanosine and blood creatinine) were analyzed. Urine samples were derivatived and analyzed by GC. Multivariate metabonomics analysis was performed after peak alignment.</p><p><b>RESULTS</b>After 8-12 weeks, losartan showed little curative effect and no remarked changes of biochemical criteria were observed. However, metabonomics analysis revealed that some biomarkers such as glucitol and inositol changed.</p><p><b>CONCLUSION</b>GC-based metabonomics analysis enables the rapid identification of metabolic differences and provides information concerning therapeutic effect of losartan.</p>

Lung cancer diagnosis based on urinary modified nucleoside metabolic profiling / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the feasibility of modified urinary nucleosides metabolic profiling on lung cancer diagnoses.</p><p><b>METHODS</b>The modified urinary nucleosides metabolic profiling from 42 normal adults and 80 patients with lung cancer were determined by a coupled-column high performance liquid chromatography system. Partial least squares-discriminant analysis (PLS-DA) models were used to class differentiation between the lung cancer patients and controls and to discover potential biomarkers.</p><p><b>RESULT</b>The PLS-DA model results showed that there was a clear differentiation between normal adults and lung cancers patients, with the value of prediction (Q2) equals to 0.744.</p><p><b>CONCLUSION</b>Modified urinary nucleosides metabolic profiling method is useful for lung cancer diagnoses.</p>

Application of urinary nucleosides in the diagnosis and surgical monitoring of colorectal cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the value of urinary normal and modified nucleosides in diagnosis and surgical monitoring of colorectal cancer (CRC).</p><p><b>METHODS</b>Between October 2002 and July 2003, 52 consecutive patients with pathological confirmed CRC were included in this study. Spontaneous urine samples were collected 1 d before and 8 d after surgery and 14 kinds of urinary nucleosides in the samples were determined by reversed-phase high-performance liquid chromatography (RP-HPLC) method. Another 62 healthy volunteers were also enrolled as controls. The routine clinical tumor markers, including serum CEA, CA199, CA125 and AFP levels of CRC patients were evaluated by electrochemical-luminescence immunoassay simultaneously.</p><p><b>RESULTS</b>The mean levels of pseudouridine (Pseu), adenosine (A), cytidine (C), 1-methyladenosine (m1A), 1-methylinosine (m1I), 3-methyluridine + 5-methyluridine (mU), 2,2-methylguanosine (m22G), inosine (I), 1-methylguanosine (m1G), N4-acetylcytidine (ac4C), N6-methyladenosine (m6A) among 14 kinds of determined urinary nucleosides in CRC group were much higher than those of controls (P < 0.05). Based on principal component analysis, 76.9% of CRC patients were correctly identified, which was much higher than that of CEA (38.5%), CA199 (40.4%), CA125 (15.4%), and AFP (17.3%) (P < 0.01). ROC curve analysis of m1G, and Pseu showed good sensitivity-specificity profiles to CRC. Two classification equations, Y(normal) = -3.009 + 0.0272 x Pseu + 4.918 x m1G and Y(CRC) = -8.057 + 0.0667 x Pseu + 8.258 x m1G, were established by Bayes stepwise discriminate analysis for predicting carcinogenesis of CRC. The elevated levels of Pseu, C, U (uridine), m1A, m1I, m1G, ac4C, A, m22G dramatically decreased after curative resection of 40 cases of CRC. And our data also showed that the preoperative levels of Pseu, m1G, m1A and m22G were positively related with tumor size and the preoperative levels of m1A, m22G and ac4C were positively related with Duke's staging of CRC (P < 0.05).</p><p><b>CONCLUSIONS</b>Normal and modified urinary nucleosides may become additional tumor markers which are feasible in the clinical setting and will prove helpful in the diagnosis, management and follow-up of CRC, and Pseu and m1G may be more promising for clinical application.</p>

Metabonomics and its applications / 生物工程学报

The concept, characteristics and history of metabonomics are introduced. The techniques used in data acquisition and data analysis in metabonomics including their advantages and disadvantages are summarized. In data acquisition platform, NMR, GC/MS, LC/MS (/MS) are the prevalent techniques although at present, none of them is a perfect technique that could meet with the requirement of the metabonomics for measuring all metabolites. While in data analysis, the PCA, PLS and ANN are the major techniques. The researchers could select them according to the research destination. Recent advances and applications of metabonomics in disease diagnosis, drug toxicity evaluation, plant metabolomics and microbial metabolomics are reviewed. In addition, by giving the situation on the establishment of the related corporations, the conferences about metabonomics and proclamation of NIH roadmap the current boom of the metabonomics is reflected. It can be expected that with the development of the function genomics, metabonomics will play a major role in the discovery of the phynotype of the genome and searching for the disease diagnostic biomarkers, and it will also bring much benefit to the drug discovery, clinical diagnosis and nutrition science.