OBJECTIVETo study metabonomic changes in plasma of tumor patients of phlegm-stasis syndrome by Chinese medicine and their in vivo metabolic mechanism.

METHODS1H nuclear magnetic resonance (NMR) based metabonomic analysis was performed on plasma samples from 356 tumor patients of the phlegm-stasis syndrome and 104 tumor patients of the non-phlegm-stasis syndrome, and 50 healthy subjects. The spectrogram integral results were analyzed by orthogonal partial least-squares discriminant analysis (OPLS-DA).

RESULTSCompared with healthy subjects, various amino acids including leucine, alanine, citrulline, tyrosine, histidine, arginine, methionine, isoleucine, valine, acetylcysteine, etc. in the plasma of patients of the phlegm-stasis syndrome were significantly lowered (P <0.05). Glucose, glycoprotein, glutamine, myo-inositol, lactic acid, choline, creatine also significantly decreased (P<0.05). But the plasma formic acid, acetone, acetic acid, acetoacetate, pyruvate, beta-hydroxy butyrate, carnitine, malonic acid, and unsaturated fatty acid, very low density lipoprotein cholesterol (VLDL-C), low density lipoprotein cholesterol (LDL-C) increased in tumor patients of the phlegm-stasis syndrome. Compared with tumor patients of non-phlegm-stasis syndrome, patients of the phlegm-stasis syndrome had obvious lower plasma contents of leucine, alanine, citrulline, tyrosine, histidine, soleucine, valine, glutamine, myo-inositol, scyllo-inositol, lactic acid, creatine (P <0. 05), higher plasma contents of acetone, acetoacetate, unsaturated fatty acid, VLDL-C, alpha-glucose, beta-glucose, glycoprotein, and so on (P <0. 05).

CONCLUSIONSTumor patients of the phlegm-stasis syndrome had strengthened in vivo fat metabolism and lowered various amino acids. The decreased antioxidation capacities resulted in aggravated cell membrane injuries. The in vivo metabolic disorder was more severe in tumor patients of the phlegm-stasis syndrome than in tumor patients of the non-phlegm-stasis syndrome.

Case-Control Studies ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Metabolomics ; Middle Aged ; Neoplasms ; diagnosis ; metabolism ; pathology ; Plasma ; metabolism

Objective To study metabonomics in the urine of rats of different genders by magnetic resonance (MR) with 2 normalization methods. Methods Different normalization methods such as mean-centering not scaling (Ctr) and unit variance scaling (UV) were used before orthogonal to partial least squares discriminant analysis(OPLS-DA). Distinguished metabolites in the urine of different gender rats were analyzed by calculating the correlation coefficients. Results The data normalized by Ctr before OPLS-DA analysis revealed high degree conception metabolites in the urine such as valine, alanine, acetate, ornithine, aminohippurate, phenylethylamine, cytosine, citrate, dimethylamine, allantoin, methylamine, fumarate and one unknown metabolite whose chemical shift was δ4.14. Data normalized by UV before OPLS-DA analysis revealed the above 12 high degree conception metabolites except citrate, and also low degree conception metabolites such as thiamine, creatinine, formate and one unknown metabolite whose chemical shift was δ2.92.Conclusion Unit variance scaling is a more effective normalization method in metabonomic analysis.

OBJECTIVETo explore in vivo metabolic changes in abnormal savda patients with different types of tumor.

METHODSA total of 142 abnormal savda patients with common cancer types were enrolled in this study, and 50 healthy volunteers were recruited as the control group. For each sample, the H Nuclear Magnetic Resonance (NMR) based metabonomic analysis was performed. The free attenuation signal was computed subsection integral. Data obtained were analyzed by the Orthogonal Partial Least-Squares Discriminant Analysis (OPLS-DA).

RESULTSCompared with the control group, leucine, isoleucine, valine, histidine, phenylalanine, tyrosine, alanine, creatine, lactic acid, inositol, alpha-and beta-glucose, unsaturated lipids, very low density lipoprotein (VLDL) significantly decreased (P <0.05), while glycoprotein and carnitine significantly increased (P <0. 05) in the abnormal Savda group.

CONCLUSIONAbnormal savda patients with different types of tumor had similar metabonomics changes.

Discriminant Analysis ; Humans ; Least-Squares Analysis ; Lipids ; blood ; Magnetic Resonance Spectroscopy ; Metabolome ; physiology ; Metabolomics ; Neoplasms ; metabolism

Objective To study the serum metabonomic changes in abnormal Savda rat model of type 2 diabetes mellitus (T2DM).Methods Sprague Dawley (SD) rats were subjected to abnormal Savda-producing conditions followed by induction of T2DM.Plasma samples were collected from each test group and analyzed by 1H nuclear magnetic resonance (NMR) spectroscopy.The spectral profiles were analyzed by multivariate analysis using orthogonal projection to latent structurs discriminant analysis (OPLS-DA).Results The content of glucose and lactic acid in plasma of the rats with abnormal Savda syndrome was decreased, while the contents of VLDL, LDL and carnitine increased obviously.For abnormal Savda rat model with T2DM, the concentration of amino acids (alanine, valine, isoleucine, leucine, tyrosine, glutamic acid, phenylalanine, methyl-histidine, glycine), and lactic acid, pyruvic acid, glycoprotein, citric acid, creatinine, β-hydroxybutyric acid, acetoacetic acid, acetic acid, acetate, creatine, carnitine, scyllo-inositol, VLDL, LDL were decreased, and glucose and taurine concentrations were increased significantly.Conclusions Protein metabolism, phenylalanine and tyrosine metabolic pathway, glycolytic pathway and the lipid metabolic pathway may be considered as biomarkers of abnormal Savda rat model of T2DM.

OBJECTIVETo investigate the plasma samples obtained from tumor patients using (1)H nuclear magnetic resonance (NMR) spectroscopy, and find the biochemical foundation of abnormal Savda described in traditional Uyghur medicine.

METHODSA total of 170 tumor patients with abnormal Savda syndrome who were confirmed clinically were enrolled in this study, and 50 healthy volunteers were set up as controls. The plasma (1)H NMR spectra were analyzed using the orthogonal projection to latent structure with discriminant analysis (OPLS-DA) method with unit variance scaling. The discriminative significance of the metabolites was determined using the Pearson's product-moment correlation coefficient.

RESULTSCompared with the healthy controls, the tumor patients with abnormal Savda syndrome had uniformly correlative low levels of leucine, isoleucine, valine, histidine, tyrosine, alanine, glutamine, creatine, inositol, α-glucose, and β-glucose (P<0.05), but had significantly high levels of formate, malonic acid, acetone, acetate, acetoacetate, pyruvate, β-hydroxy butyrate, carnitine and lipidtemns such as very low density lipoprotein, low density lipoprotein and unsaturated lipids (P<0.05).

CONCLUSIONTumor patients with abnormal Savda syndrome had similar metabolic changes and characteristics, which indicated a similar pathogenetic process and provides some biochemical basis for traditional Uyghur medicine theory.

Blood Chemical Analysis ; methods ; Case-Control Studies ; Disease ; etiology ; Humans ; Magnetic Resonance Spectroscopy ; methods ; Medicine, Chinese Traditional ; methods ; Metabolomics ; methods ; Models, Theoretical ; Neoplasms ; blood ; classification ; etiology ; metabolism ; Protons ; Syndrome

OBJECTIVETo analyze the metabonomic (1)H-MRS of plasma samples from patients with esophageal cancer and healthy controls applying different pattern recognition methods, and to explore the potential of application of (1)H-MR-based metabonomics in clinical research.

METHODS(1)H-MR was performed on plasma samples from 109 EC patients and 50 health controls to analyze the metabonomic variation between EC patients and healthy subjects and the corresponding (1)H-MRS were recorded on Varian Unity ANOVA 600 MHz to perform principal components analysis (PCA), partial least squares discriminant analysis (PLS-DA), orthogonal partial least squares discriminant analysis (OPLS-DA), respectively.

RESULTSOPLS-DA analysis could correctly separate almost all the plasma samples from EC patients and health controls, better than both the PCA and PLS-DA. The plasma levels of leucine, alanine, isoleucine, valine, glycoprotein, lactate, acetone, acetate, choline, isobutyrate, unsaturated lipid, VLDL, LDL, 1-methylhistidine were significantly decreased in EC patients (r total > 0.27, P < 0.05), while that of dimethylamine, α-glucose, β-glucose, citric acid increased in the EC patients (r total < -0.27, P < 0.05).

CONCLUSIONSThe analysis of metabonomic (1)H-MRS of plasma samples by OPLS-DA method can eliminate the influence of non-experimental factors and decrease the heterogeneity of samples. It is useful and of great potential for application in clinical diagnosis and research of esophageal cancer.

Adult ; Aged ; Blood Chemical Analysis ; China ; ethnology ; Discriminant Analysis ; Esophageal Neoplasms ; blood ; Female ; Humans ; Least-Squares Analysis ; Magnetic Resonance Spectroscopy ; Male ; Metabolomics ; Middle Aged ; Plasma ; metabolism ; Principal Component Analysis

OBJECTIVE: To investigate gender variability in the metabolic serum and urinary profile of healthy Han population in Xinjiang. METHODS: Serum and urinary samples from 92 healthy Han people in Xinjiang were tested by magnetic resonance based metabonomics and pattern recognition analysis performed with orthogonal partial least-squares discriminant analysis (OPLS-DA). The quality of the model was described by parameter R(2)X, R(2)Y, and Q(2). RESULTS: The serum in males had higher levels of very low density lipoprotein, low density lipoprotein, unsaturated lipids, creatinine and acetone than in females, whereas females had higher levels of citrate, choline, glucose and amino acids (including isoleucine, leucine, valine, alanine, citrulline, lysine, methionine, glutamate, phenylalanine, threonine, tyrosine, 1-methyl histidine and glycine) than in males. The urine of males had higher levels of formate, malonic acid, taurine, creatinine than that of females, while females had higher levels of hippurate, γ-aminobutyric acid, succinate, citrate and glutamate than males. The model parameters of serum were R(2)X=0.64, R(2)Y=0.70, and Q(2)=0.67, and those of urine were R(2)X=0.17, R(2)Y=0.70, and Q(2)=0.44. CONCLUSION The blood and urine from Han population in Xinjiang contain a variety of gender related metabolites, which plays an important role in the research of clinical metabonomics.
Amino Acids ; blood ; urine ; Blood Chemical Analysis ; China ; ethnology ; Citric Acid ; blood ; urine ; Creatinine ; blood ; urine ; Female ; Humans ; Lipids ; blood ; urine ; Lipoproteins ; blood ; urine ; Magnetic Resonance Spectroscopy ; Male ; Metabolome ; Metabolomics ; methods ; Sex Factors ; Urinalysis

OBJECTIVETo investigate the metabonomic variation between patients with esophageal cancer (EC) and healthy controls, and to analyze the variation between patients with EC.

METHODSH-MR and orthogonal partial least-squares discriminant analysis (OPLS-DA) was performed on 108 plasma specimens from EC patients and 50 health controls, and the metabonomic variation between patients with EC and healthy controls analyzed.

RESULTSOPLS-DA analysis might correctly separate all plasma specimens from health controls and patients with EC, leucine (0.0043 +/- 0.0006, 0.0040 +/- 0.0006), alanine (0.0039 +/- 0.0007, 0.0033 +/- 0.0006), isoleucine (0.0067 +/- 0.0010, 0.0063 +/- 0.0009), valine (0.0037 +/- 0.0005, 0.0035 +/- 0.0006), glycoprotein (0.0123 +/- 0.0043, 0.0102 +/- 0.0022), lactate (0.0342 +/- 0.0113, 0.0258 +/- 0.0085), acetone (0.0027 +/- 0.0023, 0.0017 +/- 0.0008), acetate (0.0007 +/- 0.0001, 0.0006 +/- 0.0001), choline (0.0035 +/- 0.0006, 0.0029 +/- 0.0007), isobutyrate (0.0020 +/- 0.0004, 0.0018 +/- 0.0003), unsaturated lipid (0.0072 +/- 0.0013, 0.0059 +/- 0.0018), VLDL (0.1209 +/- 0.0589, 0.0879 +/- 0.0269), LDL (0.0885 +/- 0.0328, 0.0785 +/- 0.0288), 1-methylhistidine (0.0005 +/- 0.0001, 0.0004 +/- 0.0005) decreased in EC patient' s plasma with statistical significance (r total > 0.27, P < 0.05), dimethylamine (0.0004 +/- 0.0001, 0.0005 +/- 0.0001), alpha-glucose (0.0079 +/- 0.0013, 0.0081 +/- 0.0016), 3-glucose (0.0139 +/- 0.0024, 0.0142 +/- 0.0029), citric acid (0.0044 +/- 0.0008, 0.0106 +/- 0.0058) increase in the EC patient's plasma (r total < -0.27, P < 0.05). There were clear variation between Han and Kazak patients, alanine (0.0031 +/- 0.0005,0.0029 +/- 0.0004), glutamine (0.0010 +/- 0.0001, 0.0009 +/- 0.0001), tyrosine (0.0009 +/- 0.0001, 0.0008 +/- 0.0001), 1-methylhistidine (0.0005 +/- 0.0001, 0.0004 +/- 0.0001) increased in the Han patients (r > 0.35, P> 0.05), carnitine (0.0028 +/- 0.0006) was higher in Kazak patients than in Han patients (0.0025 +/- 0.0004), which had statistical significance (r = - 0.40, P < 0.05). Unsaturated lipid (0.0059 +/- 0.0018, 0.0047 +/- 0.0011), isoleucine (0.0062 +/- 0.0011, 0.0058 +/- 0.0007), alanine (0. 0032 +/- 0.0007, 0.0028 +/- 0.0004), glycoprotein (0.0096 +/- 0.0019, 0.0086 +/- 0.0011), glutamine (0.0011 +/- 0.0001, 0.0009 +/- 0.0001), tyrosine (0.0009 +/- 0.0001, 0.0008 +/- 0.0001), 1-methylhistidine (0.0005 +/- 0.0001, 0.0004 +/- 0.0001) were increased in Uygur patients as compared with Kazak patients, having statistical significance (r > 0.33, P < 0.05), carnitine (0.0027 +/- 0.0005) was higher in Kazak patients than in Uygur patients (0.0025 +/- 0.0004) (r = - 0.36, P < 0.05).

CONCLUSIONThe results indicate that 1H-MR spectra of plasma analyzed by OPLS-DA statistical methods might completely separate the EC patients from health controls. The metabonomic approach should be helpful in screening of EC patients.

Adult ; Aged ; Case-Control Studies ; China ; epidemiology ; ethnology ; Esophageal Neoplasms ; blood ; epidemiology ; ethnology ; Female ; Humans ; Least-Squares Analysis ; Magnetic Resonance Spectroscopy ; Male ; Metabolomics ; Middle Aged ; Plasma ; metabolism

Objective To evaluate and discuss the changes of biomarkers of abnormal Savda syndrome rat model in Uyghur traditional medicine by external feature observation and urine metabolomics assessment. Methods The abnormal Savda syndrome rat model was established according to the theory of Uyghur traditional medicine. Its external characteristics such as hair, tongue, sleep, feces, emotion and weight growth rate were observed and scored, and their urine was detected and analyzed by proton nuclear magnetic resonance(1H-NMR)spectroscopy. Results Compared with the healthy control group,there were significant changes in the external features in the abnormal Savda syndrome rat model group,including dry and hard stools,reduced urine output and darker color,dry fur,dark purple tongue with ecchymosis, and decreased weight growth rate. Moreover,23 urinary metabolites were significantly reduced,including propionate,lactic acid, pyruvic acid, acetic acid, alanine, acetamide, glycoprotein, acetone, methyl guanidine, sarcosine, ornithine, glycine, creatine, creatinine, aminoanhydride, β-galactose, urocanate, tyrosine, phenylalanine, hippuric acid, aminohippuric acid,formic acid and lysine. However,urea,citric acid,allantoin and α-ketoglutaric acid were significantly increased. Conclusions During the development process of Savda syndrome, there are not only abnormal changes in external appearance in the model rats, but also evident changes of many internal metabolic pathways. The obvious abnormalities of the urine metabolites may be related to the biological mechanisms of abnormal Savda syndrome.

OBJECTIVE: To determine the plasma amino acid metabolism of "same symptom for different diseases" in different cancer patients in Uyghur medicine. METHODS: Plasma amino acid concentration was tested by high-performance liquid chromatography (HPLC) in cancer patients with different symptom, and the spectral profiles were subjected to a t-test for statistical significance. RESULTS: Compared with the healthy group, lung cancer, cervical cancer, breast cancer and gastric cancer patients with abnormal Savda had lower concentration of plasma amino acids except some amino acids. Lung cancer patients with abnormal Savda had higher concentration of plasma phenylalanine, serine, cystine, valine, isoleucine, leucine and aspartic acid than Unsavda patients (P<0.05). Cervical cancer patients with abnormal Savda had low concentration of plasma arginine, but higher concentration of plasma cystine than Unsavda patients (P<0.05). Breast cancer patients with abnormal Savda had higher concentration of plasma leucine, serine, taurine, cystine, tyrosine, valine, isoleucine and asparagine than Unsavda patients (P<0.05). Gastric cancer patients with abnormal Savda had high concentration of plasma cystine but lower concentration of plasma phenylalanine, threonine and arginine than Unsavda patients (P<0.05). CONCLUSION Different tumor patients with abnormal Savda have common characteristics and significant differences.
Amino Acids ; blood ; Arginine ; Aspartic Acid ; Chromatography, High Pressure Liquid ; Cystine ; Humans ; Isoleucine ; Leucine ; Medicine, Chinese Traditional ; Neoplasms ; blood ; Serine ; Tyrosine ; Valine