This study aims to reveal the endogenous metabolic characteristics of acteoside in the young rat model of purinomycin aminonucleoside nephropathy(PAN) by non-targeted urine metabolomics and decipher the potential mechanism of action. Biochemical indicators in the urine of rats from each group were determined by an automatic biochemical analyzer. The potential biomarkers and related core metabolic pathways were identified by ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) combined with principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). MetaboAnalyst 5.0 was used to establish the receiver operating characteristic(ROC) curve for evaluating the clinical diagnostic performance of core metabolites. The results showed that acteoside significantly decreased urinary protein-to-creatinine ratio in PAN young rats. A total of 17 differential metabolites were screened out by non-targeted urine metabolomics in PAN young rats and they were involved in phenylalanine metabolism and phenylalanine, tyrosine and tryptophan biosynthesis. Thirtten differential metabolites were screened by acteoside intervention in PAN young rats, and they were involved in phenylalanine metabolism and arginine and proline metabolism. Among them, leucylproline and acetophenone were the differential metabolites that were significantly recovered after acteoside treatment. These pathways suggest that acteoside treats PAN in young rats by regulating amino acid metabolism. The area under the curve of two core biomarkers, leucylproline and acetophenone, were both greater than 0.9. In summary, acteoside may restore amino acid metabolism by regulating endogenous differential metabolites in PAN young rats, which will help to clarify the mechanism of acteoside in treating chronic glomerulonephritis in children. The characteristic biomarkers screened out have a high diagnostic value for evaluating the treatment of chronic glomerulonephritis in children with acteoside.
Humans ; Child ; Rats ; Animals ; Puromycin Aminonucleoside ; Metabolomics/methods* ; Biomarkers/urine* ; Chromatography, High Pressure Liquid/methods* ; Acetophenones ; Glomerulonephritis ; Phenylalanine ; Amino Acids

Adolescent ; Amino Acids ; urine ; Child ; Female ; Humans ; Kashin-Beck Disease ; urine ; Male ; Metabolomics

Diabetic nephropathy is one of the various complications of diabetes mellitus, affecting patients for lifetime. Earlier studies have revealed that genipin can not only improve diabetes, but also induce cytotoxicity. Therefore, it is not clear which effect of genipin on kidneys occurs, when it is used in the treatment of diabetes. In the present study, we performed nuclear magnetic resonance (NMR)-based metabolomics analysis of urine and kidney tissue samples obtained from diabetic rats to explore the change of endogenous metabolites associated with diabetes and concomitant kidney disease. Nine significant differential metabolites that were closely related to renal function were screened. They were mainly related to three metabolic pathways: synthesis and degradation of ketone bodies, glycine, serine and threonine metabolism, and butanoate metabolism, which are involved in methylamine metabolism, energy metabolism and amino acid metabolism. In addition, after the intervention of genipin, the metabolic levels of all the metabolites tended to be normal, indicating a protective effect of genipin on kidneys. Our results may be helpful for understanding the antidiabetic effect of genipin.
Amino Acids ; metabolism ; Animals ; Diabetes Mellitus, Experimental ; chemically induced ; drug therapy ; metabolism ; urine ; Energy Metabolism ; drug effects ; Hypoglycemic Agents ; pharmacology ; Iridoids ; pharmacology ; Kidney ; drug effects ; metabolism ; Male ; Metabolic Networks and Pathways ; drug effects ; Metabolome ; drug effects ; Metabolomics ; Methylamines ; metabolism ; Proton Magnetic Resonance Spectroscopy ; Rats ; Rats, Sprague-Dawley

External quality assessment (EQA) trials of conventional newborn screening tests for phenylketonuria, galactosemia, congenital adrenal hyperplasia, maple syrup urine disease, homocystinuria, and congenital hypothyroidism, as well as extended newborn screening tests using tandem mass spectrometry, were performed twice in 2016 and 2017. A total of 44 specimens in the form of dried blood spots were distributed in each trial to 16 laboratories. The response rate of these laboratories was 100%. The mean, standard deviation, coefficient of variation, median, and cut-offs were evaluated for each analyte in the newborn screening tests. EQA trials for the analyses of methylmalonic acid, vanillylmandelic acid, catecholamines, metanephrines, organic acids, and amino acids were also performed. A well-designed EQA program and continuous education would improve the performance of metabolite testing.
Adrenal Hyperplasia, Congenital ; Amino Acids ; Catecholamines ; Congenital Hypothyroidism ; Education ; Galactosemias ; Homocystinuria ; Humans ; Infant, Newborn ; Korea* ; Maple Syrup Urine Disease ; Mass Screening ; Methylmalonic Acid ; Phenylketonurias ; Tandem Mass Spectrometry ; Vanilmandelic Acid

Kashin-Beck disease (KBD) is an endemic degenerative osteoarthropathy of uncertain etiology. The aim of our study was to identify changes in C-telopeptide of type II collagen (CTX-II), pyridinoline (PYD), and deoxypyridinoline (DPD) among KBD patients. 54 KBD patients and 78 healthy controls were included this study. Urinary samples were collected and measured by ELISA. The median quantities of PYD, CTX-II, and DPD of KBD patients were 1107.73 ng/μmol.cre, 695.11 ng/μmol.cre, and 1342.34 pml/μmol.cre, while the median quantities of healthy controls were 805.59 ng/μmol.cre, 546.47 ng/μmol.cre, and 718.15 pml/μmol.cre, respectively. The differences between KBD patients and healthy controls were statistically significant (Z = 4.405, 3.653, and 3.724; P < 0.001). The higher levels of PYD, CTX-II, and DPD detected in KBD patients indicate that they could be used as biomarkers of KBD.
Adult ; Amino Acids ; urine ; Biomarkers ; urine ; China ; Collagen Type II ; urine ; Female ; Humans ; Kashin-Beck Disease ; diagnosis ; urine ; Male ; Middle Aged ; Peptide Fragments ; urine

Two external quality assessment (EQA) trials of conventional newborn screening tests for phenylketonuria, galactosemia, congenital adrenal hyperplasia, maple syrup urine disease, homocystinuria, and congenital hypothyroidism, as well as newborn screening tests using tandem mass spectrometry, were performed in 2015. A total of 44 specimens in the form of dried blood spots were distributed to 16 laboratories and the response rate of these laboratories was 100%. The mean, standard deviation, coefficient of variation, median, and cut-offs were evaluated for each analyte in the newborn screening tests. Two EQA trials for the analyses of methylmalonic acid, vanillylmandelic acid, catecholamines, metanephrines, organic acids, and amino acids were also performed. A well-designed EQA program and continuous education would improve the performance of biochemical genetics tests.
Adrenal Hyperplasia, Congenital ; Amino Acids ; Catecholamines ; Congenital Hypothyroidism ; Education ; Galactosemias ; Homocystinuria ; Humans ; Infant, Newborn ; Korea* ; Maple Syrup Urine Disease ; Mass Screening ; Methylmalonic Acid ; Molecular Biology* ; Phenylketonurias ; Tandem Mass Spectrometry ; Vanilmandelic Acid

Two trials of external quality assessment (EQA) of conventional newborn screening tests for phenylketonuria, galactosaemia, congenital adrenal hyperplasia, maple syrup urine disease, homocystinuria, and congenital hypothyroidism, as well as newborn screening tests were performed using tandem mass spectrometry in 2014. A total of 39 specimens in the form of dried blood spots were distributed to 16 laboratories and the response rate of these laboratories was 100%. Screening tests for phenylketonuria and congenital hypothyroidism did not meet the accepted performance criteria in some laboratories. The mean, standard deviation, coefficient of variation, median, and cut-offs were evaluated for each analyte in the newborn screening tests. Two trials of EQA for the analyses of methylmalonic acid, vanillylmandelic acid, catecholamines, metanephrines, organic acids, and amino acids were also performed. A well-designed EQA program and continuous education would improve the performance of biochemical genetic testing.
Adrenal Hyperplasia, Congenital ; Amino Acids ; Catecholamines ; Congenital Hypothyroidism ; Education ; Homocystinuria ; Humans ; Infant, Newborn ; Korea ; Maple Syrup Urine Disease ; Mass Screening ; Methylmalonic Acid ; Molecular Biology* ; Phenylketonurias ; Tandem Mass Spectrometry ; Vanilmandelic Acid

BACKGROUND/AIMS: Proton pump inhibitors (PPIs) act by irreversibly binding to the H+-K+-ATPase of the proton pump in parietal cells and may possibly affect the vacuolar H+-ATPase in osteoclasts. METHODS: We investigated the effect of 8 weeks of PPI treatment on the parameters of bone turnover and compared PPI with revaprazan, which acts by reversibly binding to H+-K+-ATPase in proton pumps. This study was a parallel randomized controlled trial. For 8 weeks, either a PPI or revaprazan was randomly assigned to patients with gastric ulcers. The parameters of bone turnover were measured at the beginning of and after the 8-week treatment period. RESULTS: Twenty-six patients (PPI, n=13; revaprazan, n=13) completed the intention-to-treat analysis. After the 8-week treatment period, serum calcium and urine deoxypyridinoline (DPD) were increased in the PPI group (serum calcium, p=0.046; urine DPD, p=0.046) but not in the revaprazan group. According to multivariate linear regression analysis, age > or =60 years was an independent predictor for the changes in serum calcium and urine DPD. CONCLUSIONS: In elderly patients, administering a PPI for 8 weeks altered bone parameters. Our study suggested that PPIs might directly alter bone metabolism via the vacuolar H+-ATPase in osteoclasts.
Aged ; Amino Acids/drug effects/urine ; Bone Remodeling/*drug effects ; Bone and Bones/*metabolism ; Calcium/blood ; Female ; Humans ; Intention to Treat Analysis ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; Osteoclasts/*metabolism ; Prospective Studies ; Proton Pump Inhibitors/*pharmacology ; Pyrimidinones/*pharmacology ; Tetrahydroisoquinolines/*pharmacology

To investigate the effect of naringenin on ovariectomy-induced postmenopausal osteoporosis comprehensively and systemically, thirty-two virgin Sprague-Dawley rats about 3-month-old were used and randomly divided into 4 groups: sham control group (Sham), OVX control group (OVX), naringenin treatment group and 17β-estradiol (E2) treatment group. After 12 weeks treatment with different drugs, 24 h urine were collected, organs were weighed and the organ indies were computed. Uterine pathological changes were observed by making paraffin section. Biochemical parameters and bone turnover markers: serum osteocalcin (BGP) and urine deoxypyridinoline (DPD) were analyzed with automatic biochemical analyzer or ELISA assay. Bone mineral density (BMD) and bone mineral content (BMC) were analyzed by DEXA, bone biomechanical properties was measured by three point bending test and the trabecular bone microarchitecture was evaluated by Micro CT. From the results, we can see that: the gaining of weight and the increasing of bone turnover markers such as serum BGP and urinary DPD could be inhibited by naringenin. The treatment could also enhance the bone strength and prevent the deterioration of trabecular microarchitecture, increase the bone volume, trabecular number and thickness, and decrease the trabecular space. The effects mentioned above were not accompanied with stimulating effects on uterus. Long-term using of naringenin had no obvious influence on other organs and the liver and kidney functions. The study suggests that naringenin had obvious antiosteoporotic effect on ovariectomized rats and it had the potential value for the treatment of postmenopausal osteoporosis.
Amino Acids ; urine ; Animals ; Bone Density ; Disease Models, Animal ; Estradiol ; pharmacology ; Estrogen Antagonists ; pharmacology ; Female ; Flavanones ; pharmacology ; Osteocalcin ; blood ; Osteoporosis ; drug therapy ; Ovariectomy ; Rats ; Rats, Sprague-Dawley ; Uterus ; pathology

Two trials of external quality assessment (EQA) of conventional newborn screening tests for phenylketonuria, galactosaemia, congenital adrenal hyperplasia, maple syrup urine disease, homocystinuria, and congenital hypothyroidism, as well as of newborn screening tests using tandem mass spectrometry were performed in 2013. A total of 32 specimens in the form of dried blood spots were distributed to 16 laboratories and the response rate of these laboratories was 100%. Total T4, free T4, 17-hydroxyprogesterone, leucine, isoleucine, galactose, methionine, alanine, C8/C2, C8/C10, and C5-OH did not meet the accepted performance criteria. The mean, standard deviation, coefficient of variation, median, and cut-offs were evaluated for each analyte in the newborn screening tests. Two trials of EQA for the analyses of methylmalonic acid, vanillylmandelic acid, very long fatty acids, organic acids, and amino acids were also performed. A well-designed EQA program and continuous education would improve the performance of biochemical genetic tests.
17-alpha-Hydroxyprogesterone ; Adrenal Hyperplasia, Congenital ; Alanine ; Amino Acids ; Congenital Hypothyroidism ; Education ; Fatty Acids ; Galactose ; Homocystinuria ; Humans ; Infant, Newborn ; Isoleucine ; Korea ; Leucine ; Maple Syrup Urine Disease ; Mass Screening ; Methionine ; Methylmalonic Acid ; Molecular Biology* ; Phenylketonurias ; Tandem Mass Spectrometry ; Vanilmandelic Acid