OBJECTIVETo study the association of ORMDL3 single nucleotide polymorphisms (SNP) with lysophosphatidylcholine (LysoPC) and apolipoprotein B (apoB) levels.

METHODSA total of 300 children diagnosed with bronchial asthma between January 2010 and December 2012 were selected for the asthma group, and 298 children diagnosed with upper respiratory tract infection in the same period were selected for the control group. Serum LysoPC and apoB levels were measured using enzyme-linked immunosorbent assay. Genotype analysis was performed using the TaqMan probe.

RESULTSLysoPC and apoB levels were significantly higher in the asthma group than in the control group (P<0.01). Among children with various genotypes of ORMDL3 gene at locus rs12603332, the asthma group had significantly higher LysoPC and apoB levels than the control group (P<0.01). Among the children with asthma, those with CC genotype had significantly higher LysoPC and apoB levels than those with CT and TT genotypes (P<0.01).

CONCLUSIONSLysoPC and apoB may intervene in the pathological process of asthma. Pro-inflammatory gene ORMDL3 SNP rs12603332 may be associated with high LysoPC and apoB levels, which leads to the occurrence of childhood asthma.

Apolipoproteins B ; blood ; Asthma ; blood ; genetics ; Child ; Child, Preschool ; Female ; Humans ; Lysophosphatidylcholines ; blood ; Male ; Membrane Proteins ; genetics ; Polymorphism, Single Nucleotide

This study was to report the effect of Tangshen Formula on phospholipids metabolism in diabetic nephropathy patients. A normal phase-HPLC-TOF/MS method was used in this study for the determination of seven species of phospholipids in human plasma. Then, the concentration changes of potential phospholipids biomarkers were discussed in diabetic nephropathy phase III and phase IV patients among different groups, including before and 3, 6 months after administration of Tangshen Formula. Significant increases of PE750, PI885, PC792, PC826, PC830, PC854 and PC802 levels were observed 6 months after administration of Tangshen Formula and conventional western medicine, as well as a decrease of LPC540 level, when compared with those before medication. Concentrations of all the potential phospholipids biomarkers showed a tendency towards normal levels; however, both the improvement degree and onset time of these compounds were not same. Additionally, Tangshen Formula treatment based on conventional western medicine treatment was more efficient in adjusting the levels of these compounds when compared with western medicine treatment alone, especially for the phase IV patients. These results indicated that Tangshen Formula was capable in regulating and improving phospholipids metabolism in diabetic nephropathy patients, which may be related with the direct or indirect inhibition of protein kinase C pathway and the corresponding reduction of phospholipase A2 activity. Therefore, Tangshen Formula may be used as an effective drug for diabetic nephropathy therapy, at least as an adjunctive therapeutic drug.
Diabetic Nephropathies ; blood ; metabolism ; Double-Blind Method ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Glycerophospholipids ; blood ; Humans ; Lysophosphatidylcholines ; blood ; Phospholipases A2 ; metabolism ; Phospholipids ; blood ; classification ; Plants, Medicinal ; chemistry ; Protein Kinase C ; metabolism ; Signal Transduction ; Sphingomyelins ; blood

BACKGROUND: Metformin is an effective oral antihyperglycaemic agent for type 2 diabetes mellitus, with a variety of metabolic effects. In addition to controlling blood glucose level, it has been appeared to decrease the long-period complications of diabetes, including macrovascular disease. Few reports have addressed the metabolite profiling of metformin. The study was to evaluate if targeted metabolic profiling approach is sensitive enough to predict the therapeutic effects of metformin after a single oral dose. METHODS: A randomized, open-label, single-dose study was conducted in twenty eight healthy Korean male volunteers. To determine the concentrations of endogenous metabolites in their pre-dose and post-dose plasma samples, blood samples were collected before and at 2 and 6 h after a single oral dose of 500 mg metformin. Both Modular P/Modular D analyzer and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)-based metabolic profiling was performed. RESULTS: We quantified pre-dose and post-dose creatinine, blood urea nitrogen (BUN), lactic acid, 7 amino acids (lysine, glutamic acid, alanine, valine, leucine, phenylalanine, tryptophan), and 5 lysophosphatidylcholines (14:0, 16:0, 17:0, 18:0, and 18:1) using autoanalyser and UPLC-MS/MS. The postdose levels of alanine, lactic acid, glutamic acid, lysine, valine, leucine, phenylalanine, tryptophan, and lysoPC (18:1) were slightly decreased with statistical significance, but there is no clinical significance. CONCLUSION: In order to explore the potential endogenous metabolites associated with the therapeutic effects of metformin, further study including non-targeted (global) metabolite profiling is needed.
Alanine ; Amino Acids ; Blood Glucose ; Blood Urea Nitrogen ; Chromatography, Liquid ; Creatinine ; Diabetes Mellitus, Type 2 ; Glutamic Acid ; Humans ; Lactic Acid ; Leucine ; Lysine ; Lysophosphatidylcholines ; Male ; Metformin ; Phenylalanine ; Plasma ; Tandem Mass Spectrometry ; Tryptophan ; Valine

BACKGROUND: Metformin is an effective oral antihyperglycaemic agent for type 2 diabetes mellitus, with a variety of metabolic effects. In addition to controlling blood glucose level, it has been appeared to decrease the long-period complications of diabetes, including macrovascular disease. Few reports have addressed the metabolite profiling of metformin. The study was to evaluate if targeted metabolic profiling approach is sensitive enough to predict the therapeutic effects of metformin after a single oral dose. METHODS: A randomized, open-label, single-dose study was conducted in twenty eight healthy Korean male volunteers. To determine the concentrations of endogenous metabolites in their pre-dose and post-dose plasma samples, blood samples were collected before and at 2 and 6 h after a single oral dose of 500 mg metformin. Both Modular P/Modular D analyzer and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)-based metabolic profiling was performed. RESULTS: We quantified pre-dose and post-dose creatinine, blood urea nitrogen (BUN), lactic acid, 7 amino acids (lysine, glutamic acid, alanine, valine, leucine, phenylalanine, tryptophan), and 5 lysophosphatidylcholines (14:0, 16:0, 17:0, 18:0, and 18:1) using autoanalyser and UPLC-MS/MS. The postdose levels of alanine, lactic acid, glutamic acid, lysine, valine, leucine, phenylalanine, tryptophan, and lysoPC (18:1) were slightly decreased with statistical significance, but there is no clinical significance. CONCLUSION: In order to explore the potential endogenous metabolites associated with the therapeutic effects of metformin, further study including non-targeted (global) metabolite profiling is needed.
Alanine ; Amino Acids ; Blood Glucose ; Blood Urea Nitrogen ; Chromatography, Liquid ; Creatinine ; Diabetes Mellitus, Type 2 ; Glutamic Acid ; Humans ; Lactic Acid ; Leucine ; Lysine ; Lysophosphatidylcholines ; Male ; Metformin ; Phenylalanine ; Plasma ; Tandem Mass Spectrometry ; Tryptophan ; Valine

A UPLC-MS/MS method based on metabonomic skills was developed to study the serum metabolic changes of rats after acute liver injury induced by CCl4 and to evaluate the action mechanism of Si-Ni-San. The integrated data were exported for principal components analysis (PCA) by using SIMCA-P software, in order to find the potential biomarkers. It showed that clear separation of healthy control group, model group, silymarin group, Si-Ni-San group was achieved by using the PCA method. Nine significantly changed metabolites were identified as potential biomarkers of acute liver injury. Compared with the health control group, the model group rats showed higher levels of phenylalanine, tryptophan and GCDCA together with lower levels of LPC 16 : 0, LPC 18 : 0, LPC 18 : 1, LPC 16 : 1, LPC 20 : 4 and LPC 22 : 6. These changes of serum metabolites suggested that the disorders of amino acid metabolism, lipid metabolism, bile acid biosynthesis and anti-oxidative damage were related to acute liver injury induced by CCl4. Si-Ni-San might have the anti-liver injury effect on all these four metabolic pathways.
Animals ; Carbon Tetrachloride Poisoning ; Chemical and Drug Induced Liver Injury ; blood ; etiology ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Glycodeoxycholic Acid ; blood ; Lysophosphatidylcholines ; blood ; Male ; Metabolomics ; Phenylalanine ; blood ; Plants, Medicinal ; chemistry ; Principal Component Analysis ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; Tryptophan ; blood

Although oxidized low-density lipoprotein (LDL) and lysophosphatidylcholine (LPC) have been proposed as important mediators of the atherosclerosis, the long-term contribution to the risk of cardiovascular disease (CVD) in hemodialysis patients has not been evaluated. This study investigated the relation between oxidized LDL and LPC levels with long term risk of CVD. Plasma oxidized LDL and LPC levels were determined in 69 Korean hemodialysis patients as a prospective observational study for 5 yr. During the observation period, 18 cardiovascular events (26.1%) occurred including 6 deaths among the hemodialysis patients. The low LPC level group (< or = 254 microM/L, median value) had much more increased risk of CVD compared to the high LPC level group (> 254 microM/L) (P = 0.01). However, serum levels of oxidized LDL were not significantly different between groups with and without CVD. In adjusted Cox analysis, previous CVD, (hazard ratio [HR], 5.68; 95% confidence interval [CI], 1.94-16.63, P = 0.002) and low LPC level (HR, 3.45; 95% CI, 1.04-11.42, P = 0.04) were significant independent risk factors for development of CVD. It is suggested that low LPC, but not oxidized LDL, is associated with increased risk of CVD among a group of Korean hemodialysis patients.
Adult ; Aged ; Asian Continental Ancestry Group ; Cardiovascular Diseases/*diagnosis/etiology/mortality ; Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; Kidney Failure, Chronic/blood/complications/diagnosis ; Lipoproteins, LDL/*blood ; Lysophosphatidylcholines/*blood ; Male ; Middle Aged ; Proportional Hazards Models ; Prospective Studies ; Renal Dialysis ; Republic of Korea ; Risk Factors