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Quantitative nuclear magnetic resonance (qNMR) technology has significant advantages in quantification due to its simple sample processing and high reproducibility. Two-dimensional qNMR analysis, which can solve the quantification problem of different components in complex systems, has gradually been applied in medicine, food, metabonomics, chemical engineering, and other fields. This paper reviews the analysis methods, influencing factors, experimental optimization, application fields, and other aspects of qNMR to promote its wide and effective application.
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"Omics" and bioinformatics have brought new ideas to the study of traditional Chinese medicine. This study used metabonomics and network pharmacology to investigate the pharmacodynamic basis and regulation of Qishen Yiqi dropping pill (QDP) improving cardiac energy metabolism in rats with heart failure (HF). 1H NMR metabonomics analysis showed that eight metabolites, including carnitine, glutamine, creatine, proline, homocitrulline, lactic acid, taurine and alanine appeared significant callback after QDP treatment for HF. The results indicate that QDP regulates the metabolism of carbohydrate, lipid, ATP and protein. The animal experiment was conducted in accordance with the regulations of the Ethics Committee for Experimental Animal Management and Animal Welfare of Institute of Materia Medica, Chinese Academy of Medical Sciences. A "drug-component-target-disease" network was established using network pharmacology, and the "component-target" sub-network related to the above energy metabolism processes was extracted by combining metabonomics results. Results revealed 79 chemical compounds and 47 potential targets of QDP involved in the regulation of energy metabolism, and identified key chemical components including ursolic acid, notoginsenoside G, ginsenoside-Rh1, and core targets such as INS, PPARG, and AKT1. The results also demonstrated the complex multi-target and multi-component relationship between QDP and HF from the perspective of energy metabolism. The molecular docking technique verified a strong interaction between some targets and chemical compounds, with affinities less than -5 kcal·mol-1. The results of this study provide useful information for the clinical application, development, and utilization of QDP.
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Studies have found that metformin is not only the preferred drug for lowering blood sugar, but also shows lipid-lowering and weight-loss effects. The purpose of this study was to use a hyperlipidemia hamster model to investigate the lipid-lowering effect of metformin and its effect on important metabolic pathways in lipid metabolism disorders. Fifty golden hamsters were divided into a control group, a model group, metformin high- and low-dose groups, and a simvastatin group. A high-fat diet was fed for 1 week to create the model, and then drug was administered for 11 weeks with the high-fat diet. Serum was taken for measurement of blood lipid and blood glucose at 2, 6, and 9 weeks after administration, and at weeks 3, 5, and 9 feces and urine were collected for 1H NMR metabolomics tests. After 11 weeks of intravenous injection of [U-13C6] glucose, serum was collected for a 13C NMR metabolic flux test. The results showed that the administration of metformin can significantly reduce blood lipids and glucose levels and can significantly affect metabolic pathways such as sugar metabolism, lipid metabolism, ketone metabolism, amino acid metabolism, and intestinal flora metabolism. The results of the metabolic flux analysis showed that the high-fat diet reduced the metabolism of tricarboxylic acids by 37.48%. After administration of low and high doses of metformin the metabolism of tricarboxylic acid increased by 98.14% and 143.10%, respectively. After administration of simvastatin tricarboxylic acid metabolism increased by 33.18%. The results indicate that metformin has a significant effect on promoting energy metabolism. This study used a combination of metabolomics and metabolic flow to explore the effect of metformin on lipid metabolism disorders and quantifies changes in the key pathway of energy metabolism-the tricarboxylic acid cycle. This study provides useful information for the study of the efficacy and mechanism of metformin, as well as a practical technical method for the screening of lipid-lowering drugs based on a hamster model.
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Heart failure is the end stage of many cardiovascular diseases. It seriously affects the safety and quality of life of nearly 40 million people worldwide. At present, the clinical and pathophysiological characteristics of some types of heart failure are unknown, and there is no effective diagnosis and treatment. In recent years, genomics, transcriptomics, epigenomics, proteomics, metabolomics and other omics technologies have been widely used in disease research, providing new opportunities for the prevention, diagnosis and treatment of diseases. These strategies have also brought hope for the reduction in heart failure mortality. Based on the current status of clinical treatment of heart failure, this article reviews the roles and potential applications of these various omics technologies and their opportunities in the study of the pathogenesis of heart failure, clinical diagnosis and treatment, and related drug pharmacodynamics and mechanism of action.
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The study was designed to explore the influence of high-fat diet on the metabolism profile of feces and intestinal contents of golden hamster to provide new information for the mechanism of drug action. Twelve golden hamsters fed with high-fat diet and twelve golden hamsters fed with normal diet were used as model group and control group, respectively. Serum samples were collected from the normal group and the model group at 2 weeks, 4 weeks and 8 weeks after the induction of high-fat diet. Serum biochemical parameters were measured in the control and model groups. The levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) levels in model group were higher than the control group. After 8 weeks, the feces and intestine contents were taken. The intestine was divided into four sections:jejunum, ileum, cecum and colon. The changes of endogenous metabolites in intestinal contents were analyzed by 1H NMR based metabolomics combined with multivariate statistical analysis to find the significant differences in metabolites. The metabolic profiles of hyperlipidemia model group and control group were significantly distinguished by the othorgonal partial least squares-discriminate analysis, (OPLS-DA). Compared with the control group, the endogenous metabolites in feces such as amino acids, fatty acids, tricarboxylic acid cycle intermediates and nucleotides related to intestinal microflora were changed significantly (PP<0.05). The data suggest that the intestinal microflora plays an important role in the development of hyperlipidemia in golden hamsters from the molecular level of metabolites. This result provides useful information for the clinical treatment of hyperlipidemia and development of hyperlipidemia drug.
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Aim To observe the effect of diabetes on carbon tetrachloride (CCl4)-induced rats chemical liv-er injury and liver fibrosis by establishing diabetes mer-ged with liver fibrosis rat model (double model). Methods High fat feeding combined with streptozoto-cin (STZ) was used to induce diabetes rat model,and liver fibrosis rat model was induced by CCl4. HE stai-ning was used to observe the rat liver pathological changes, and Western blot and q-PCR were used to detect liver fibrosis related factor genes α-SMA and Collagen Ⅰ expression. Results Compared with con-trol group, diabetes group, liver fibrosis group and double model group all had different levels of liver damage,especially double model group. Rat liver tis-sues of α-SMA and CollagenⅠexpression from differ-ent model groups also increased, especially those from double model group, and significant differences were detected compared to diabetes and liver fibrosis group. Conclusions Diabetes can cause liver damage and in-crease the occurrence and development of CCl4-in-duced rats liver fibrosis, and the mechanism may be related to the formation and/or degradation of extracel-lular matrix.
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NMR-based metabolomics technique has been applied to botanical studies in recent years. The plant metabolites are complicated and various, metabolomics method can detect the global metabolomic profile of the plant to track valuable metabolites, and provide information for the research of plant physiology, metabolic pathways and functional genes. This paper reviews the application of NMR-based metabolomics technique in medicinal plants, including the biosynthetic mechanism and production of secondary metabolites, the improvement of yield or quality of medicinal plants, the development of effective active ingredient, the identification of medicinal plant species, and the quality control of herbal medicine. In addition, the potential development of this technique in future is discussed.
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Objeetive As to the high incidence of arteriovenous fistula(AVF) stenosis,surgical operation will result in the exhaustion of vascular resources in patients,while percutaneous transluminal angioplasty(PTA) can maintain vascular resources for ostomy.However,there is still no clear definition between the choices of PTA and surgical resection.The aim of this study was to compare the efficacy of PTA and surgical resection followed by reconstruction for the treatment of arteriovenous fistula stenosis in order to find appropriate treatment.Methods Retrospective analysis had been done on 46 hemodialysis patients with arteriovenous fistula stenosis in Nanjing BenQ hospital from January 2015 to March 2017,which included 22 cases treated with PTA (PTA group) and 24 cases treated with surgical operation (operation group).Comparison was made in general clinical situation,patency rate at six months after surgery,over patency time and adverse reactions to surgery between the two groups.Results The number of stenoses in PTA group was bigger than that in operation group and the difference was of statistic significance (2.78±1.43 vs 1.67±0.71,P＜0.05).There was no significant difference in patency rate between the two groups (P =0.828).There were 57 venous stenoses in PTA group,among which 12 stenoses were anastomotic (21.05％) with 79.3％ average stenosis degree and 43 stenoses were at venous outflow tract of fistula (75.44％) with 84.26 average stenosis degree.In PTA group,3 patients had hematoma brachial puncture position and recovered by self-absorption without special treatment.In operation group,1 patient had mild blood oozing and recovered after treatment;4 patients recovered gradually from mild swelling on the back of the hand of the operation side.No difference was found in adverse reactions between two groups (P＞0.05).Conclusion PTA treatment is preferred for multiple stenoses(n ≥ 3),which ensures better preservation of vascular resources at a comparable patency rate.
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Objective To establish a method for determination of accessories lactose by HPLC-RID.Methods Boston Green Amino-NH2 column (250 mm× 4.6 mm,5 μm) was used.The mobile phase was acetonitrile-water (70:30).The flow rate was 1.0 mL/min.The column temperature was 45 ℃,the detector temperature was 40 ℃ and the injection volume was 10 μL.Results Lactose showed good linearity in the range of 0.2-5.0 mg/mL (r≥0.999 8).The detection limit was 0.06 mg/mL.The average recovery was 99.6％ and the relative standard deviation was 0.7％.Conlusion The method is specific,convenient,fast and accurate,which can be used for determination of accessories lactose.
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Objective To establish a method for determination of accessories lactose by HPLC-RID.Methods Boston Green Amino-NH2 column (250 mm× 4.6 mm,5 μm) was used.The mobile phase was acetonitrile-water (70:30).The flow rate was 1.0 mL/min.The column temperature was 45 ℃,the detector temperature was 40 ℃ and the injection volume was 10 μL.Results Lactose showed good linearity in the range of 0.2-5.0 mg/mL (r≥0.999 8).The detection limit was 0.06 mg/mL.The average recovery was 99.6％ and the relative standard deviation was 0.7％.Conlusion The method is specific,convenient,fast and accurate,which can be used for determination of accessories lactose.
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OBJECTIVE: To investigate the inhibitory effects of caffeic acid phenethyl ester (CAPE) on LPS-induced inflammatory responses in BV-2 microglial cells and its mechanism.
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Nuclear magnetic resonance (NMR) spectroscopy can be used to both identify and quantify chemicals from complex mixtures. Over the last several decades, significant technical and experimental advances have made quantitative nuclear magnetic resonance (qNMR) a valuable analytical tool for quantitative measurements of a wide variety of samples. This particular approach is now being exploited to characterize the metabolomes of many different biological samples and is called quantitative metabolomics or targeted metabolic profiling. In this review, some of the strengths, limitations of NMR-based quantitative metabolomics will be discussed as well as the practical considerations necessary for acquisition with an emphasis on their use for bioanalysis. Recent examples of the application of this particular approach to metabolomics studies will be also presented.
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Magnetic Resonance Spectroscopy , Metabolome , Metabolomics , MethodsABSTRACT
2', 3', 5'-Tri-O-acetyl-N6-(3-hydroxylaniline)adenosine (WS070117) is a derivative compound of natural product cordycepin. It has significant lipids regulating activity and low toxicity which has been proved by in vitro and in vivo experiments. In this study, 1H NMR-based metabolomics was used to investigate the dose-related effects of WS070117 on hyperlipidemia of high-fat-fed hamsters. The hyperlipidemic hamsters were administrated with six different doses of WS070117, including 3, 12, 50, 100, 200 and 400 mg x kg(-1) x d(-1). 1H NMR spectra of hamster serum were visually and statistically analyzed using two multivariate analyses: principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). As a result, WS070117-treated groups showed dose-related regulation of metabolites associated with lipid metabolism, choline metabolism and glucose metabolism. The dose of 3 mg x kg(-1) x d(-1) of WS070117 only exhibited a little lipids regulating activity. However, the doses of 12 and 50 mg x kg(-1) x d(-1) of WS070117 both regulated the contents of metabolites to reverse significantly toward normal levels. When the dose of WS070117 reached 100 mg x kg(-1) x d(-1), it was more effective than positive control drugs. The work suggested that NMR-based metabolomics might be a valuable approach to evaluate dose-related effects of lipids regulating compounds.
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Animals , Cricetinae , Adenosine , Pharmacology , Hyperlipidemias , Metabolism , Least-Squares Analysis , Lipid Metabolism , Magnetic Resonance Spectroscopy , Metabolomics , Multivariate Analysis , Principal Component AnalysisABSTRACT
The application of HPLC-NMR-MS hyphenated technique in the structural identification of trace substances from complex mixtures and the identification of endogenous and exogenous substances in the establishment process of metabolic profiling have become effective analytical tools in pharmaceutical chemistry, pharmacological and pharmacokinetic studies of active substances from natural products. Metabolomics method based on NMR technology can accurately portray metabolic phenotypes with the characteristics of diseases and a variety of disease-related pathways, and it can greatly enrich and supplement the traditional disease evaluation methods. So it can be used for pharmacological studies of active substances from natural products, such as toxicological studies, the dose optimization, active substances screening and pharmacodynamic evaluation. Hyphenated technique associated with metabolomics method based on NMR technology will accelerate the speed of the discovery of active substances from natural products, and improve the efficiency of their pharmacological evaluation.
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Biological Products , Chemistry , Pharmacology , Chemistry, Pharmaceutical , Chromatography, High Pressure Liquid , Combinatorial Chemistry Techniques , Magnetic Resonance Spectroscopy , Mass Spectrometry , Metabolomics , Methods , Molecular StructureABSTRACT
To obtain a better understanding of the progression of atherosclerosis and identify potential biomarkers, proton nuclear magnetic resonance spectroscopy (1H NMR)-based metabonomics was used to study the metabolic changes in the plasma of hamster fed with a high-fat/cholesterol diet. Plasma samples were collected at different time points during the progression of atherosclerosis and individual proton NMR spectra were visually and statistically assessed using multivariate analyses. NMR results for all samples showed a time-dependent development from physiological to pathophysiological status during atherosclerosis. Analysis of the identified biomarkers of atherosclerosis suggests that lipid and amino acid metabolisms are significantly disturbed, together with inflammation, oxidative stress, following cholesterol overloading. The results enriched our understanding of the mechanism of atherosclerosis and demonstrated the effectiveness of the NMR-based metabonomics approach to study such a complex disease.
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Animals , Male , Amino Acids , Blood , Biomarkers , Metabolism , Cholesterol , Blood , Coronary Artery Disease , Blood , Metabolism , Disease Models, Animal , Disease Progression , Lipids , Blood , Magnetic Resonance Spectroscopy , Mesocricetus , Metabolome , Metabolomics , Oxidative Stress , Principal Component Analysis , Random AllocationABSTRACT
<p><b>OBJECTIVE</b>To investigate the prevalence and distributing feature of chronic heart failure (CHF) in adult population of Xinjiang.</p><p><b>METHODS</b>Four-stage random sampling method was used to analyze the prevalence and distributing feature of self-reported congestive heart failure among different nationalities in adult (35 years and over) population of Xinjiang. Sampling was collected from 6 localities (Urumqi, Kelamayi, Fukang, Turfan Basin, Hetian, Yili Hazakh).</p><p><b>RESULTS</b>A total of 8459 adults were surveyed. The prevalence of CHF was 1.26% in this cohort. The prevalence of CHF was 0.89%, 1.11% and 2.14%(*) in Han, Uygur and Hazakh population, respectively ((*)P < 0.05 vs. Han and Uygur). The risk of CHF was higher in the males than in the females (1.61% vs. 0.93%, u = 2.79, P < 0.05). The prevalence of CHF increased in proportion with aging and was 0.29%, 0.60%, 1.32%, 2.55% and 4.10% in 35 - 44, 45 - 54, 55 - 64, 65 - 74, 75 years and over age groups, respectively. Common complications of CHF were hypertension (63.55%), coronary heart disease (42.99%), diabetes (18.69%), valvular heart disease (5.61%) and atrial fibrillation (4.67%).</p><p><b>CONCLUSION</b>The prevalence of CHF in Xinjiang was higher than the average level in China (0.9%) and was the highest in the Hazakh population.</p>
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Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Asian People , China , Epidemiology , Chronic Disease , Heart Failure , Epidemiology , PrevalenceABSTRACT
Objective To investigate the relationship between stroke and ankle-brachial index (ABI), pulse wave velocity (PWV) in Han, Uighur, and Kazakh populations of Xinjiang. Methods Data was from the investigation of cardiovascular risk survey (CRS) program among different nationalities in Xinjiang from October 2007 to March 2010. A total of 14 618 samples aged over 35 with complete data dimension were surveyed. Results ( 1 ) There were 633 patients with stroke, including 258 Hans (4.48%), 247 Uighurs (5.18%), and 128 Kazakhs (3.13%). The incidence of stroke was significant different in the three ethnic groups (P＜0.001). (2)Compared to the Han population, the incidence of stroke was higher ( OR= 1.304) in Uighur but lower (OR=0.794) in Kazakh. (3) PWV was significant different between stroke and non-stroke patients. After adjustment for age, body mass index, systolic blood pressure, triglyceride, total cholesterol and other risk factors, the difference remained significant, indicating that PWV (OR=1.001, P＜0.001) might associate with the occurrence of stroke. Conclusion The results of this study showed that the incidence of stroke was significantly different in the three ethnic groups. PWV might associate with the occurrence of stroke.
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<p><b>OBJECTIVE</b>To analyze the relationship between P-glycoprotein function in peripheral blood cells and primary multidrug resistance in breast carcinoma.</p><p><b>METHODS</b>P-gp function was investigated by flow cytometry in NK cells of 16 breast cancer patients treated with anthracyclines and taxanes. Among all the patients, 8 were in chemotherapy-sensitive group and 8 in chemotherapy-resistant group. P-gp function was determined by rhodamine 123 (Rh123)-ejection test. Mathematical model was established by a regression of the fluorescence-time curve. The efflux rate constants of the chemotherapy-sensitive and -resistant groups were compared.</p><p><b>RESULTS</b>There was no significant difference of Rh123 accumulation, retention or efflux between the two groups. The mathematical model of F(t) = F(0) · e(-kt) was established. K was the efflux rate constant, which was significantly different between the chemotherapy-sensitive and -resistant groups (P = 0.025). When k > 3.9 was used as diagnostic criterium for primary resistance, the sensitivity, specificity and accuracy were 75.0%, 100% and 87.5%, respectively.</p><p><b>CONCLUSION</b>P-glycoprotein function in peripheral blood cells is associated with primary multidrug resistance in breast carcinoma. The efflux rate constant may be a good predictor for chemotherapy sensitivity.</p>
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Adult , Aged , Female , Humans , Middle Aged , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Blood , Anthracyclines , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Breast Neoplasms , Drug Therapy , Metabolism , Pathology , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Killer Cells, Natural , Metabolism , Retrospective Studies , Rhodamine 123 , Metabolism , TaxoidsABSTRACT
<p><b>OBJECTIVE</b>To investigate the association between the polymorphisms and haplotypes of prostacyclin synthase gene with MI in Uigur patients in Xinjiang.</p><p><b>METHODS</b>210 patients with MI and 206 healthy control subjects were genotyped for 3 SNPs of the human prostacyclin synthase gene by polymerase chain reaction and restriction fragment length polymorphism.</p><p><b>RESULTS</b>The genotype distributions of the control group and MI group were in the Hardy-Weinberg equilibrium (both P > 0.05). The frequency of CC of rs5629 in MI group was significantly higher than that in controls (71.42% vs. 61.65%, P = 0.035). The frequency of A-C-T haplotype was significantly higher in the control group than that in the MI patients (4.01% vs. 0.60%, P = 0.001). The frequency of C-T-T haplotype was significantly higher in the MI patients than that in the controls (7.40% vs. 3.31%, P = 0.011). Logistic regression analysis showed that, after adjusting hypertension, hyperlipemia and smoking, the CC genotype of rs5629 (P = 0.021, OR = 1.665, 95%CI: 1.024 - 2.156) and the C-T-T haplotype (P = 0.011, OR = 1.876, 95%CI: 1.410 - 3.171) was the independent risk factors for MI.</p><p><b>CONCLUSION</b>The CC genotype of rs5629 and the C-T-T haplotype of prostacyclin synthase gene are associated with MI but the A-C-T haplotype of prostacyclin synthase gene might be a protective factor of MI in Uigur population of Xinjiang.</p>
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Aged , Female , Humans , Male , Middle Aged , Asian People , Genetics , Cytochrome P-450 Enzyme System , Genetics , Gene Frequency , Genotype , Haplotypes , Intramolecular Oxidoreductases , Genetics , Myocardial Infarction , Ethnology , Genetics , Polymorphism, Single NucleotideABSTRACT
Objective The aim of this study was to assess the association between human CYP4F2 gene and myocardial infarction (MI),using a haplotype-based case-control study. A separate analysis on gender was also carried out. Methods There were 250 MI patients and 250 control subjects genotyped for 5 SNPs of the human CYP4F2 gene (rs3093105, rs3093135, rs1558139, rs2108622, rs3093200). Data were assessed on 3 separate groups: the total subjects, men and women. Results For men, G allele was significantly higher in the MI patients than in the control subjects and the overall distribution of the haplotypes was significantly different between the MI patients and the control subjects (P=0.002). Also in men, the frequency of T-C-G haplotype was significantly higher for MI patients than for control subjects (P=0.002), and the frequency of T-C-A haplotype was significantly lower for M1 patients than for control subjects (P=0.003). Conclusion Data from the present results indicated that MI was associated with G allele of rs2108622 in men, suggesting that T-C-G haplotype might serve as genetic marker for MI in men.