Serum metabolomics of chronic obstructive pulmonary disease with lung-Qi deficiency syndrome / 中国中药杂志

The present study analyzed the potential biomarkers of chronic obstructive pulmonary disease(COPD) with lung-Qi deficiency syndrome by non-targeted metabolomics and explored the biological basis of this syndrome. Blood samples of 96 COPD patients with lung-Qi deficiency syndrome(COPD with lung-Qi deficiency syndrome group) and 106 healthy people(healthy control group) were collected, and the metabolic profiles of both groups were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Multivariate statistical analysis and differential metabolite screening were carried out by using Progenesis QI and Simca-P. Metabolic pathways were constructed through the MetaboAnalyst. Seven potential biomarkers, such as L-cystathionine, protoporphyrinogen Ⅸ, and citalopram aldehyde, were identified. Compared with the results in the healthy control group, the content of citalopram aldehyde, N1-methyl-2-pyridone-5-carboxamide, and 11β,17β-dihydroxy-4-androsten-3-one was significantly up-regulated, while that of the other four compounds such as L-cystathionine, dihydrotestosterone, protoporphyrinogen Ⅸ, and D-urobilinogen was down-regulated. These potential biomarkers involved six metabolic pathways, including cysteine and methionine metabolism, porphyrin and chlorophyll metabolism, drug metabolism of cytochrome P450, steroid hormone biosynthesis, glycine, serine, and threonine metabolism, and nicotinate and nicotinamide meta-bolism. This study is expected to provide a certain scientific basis for the research on traditional Chinese medicine syndrome of COPD with lung-Qi deficiency syndrome from the molecular biology level.

Beneficial Role of Hydrogen Sulfide in Renal Ischemia Reperfusion Injury in Rats

PURPOSE: Hydrogen sulfide (H2S) is an endogenous gaseous molecule with important physiological roles. It is synthesized from cysteine by cystathionine γ-lyase (CGL) and cystathionine β-synthase (CBS). The present study examined the benefits of exogenous H2S on renal ischemia reperfusion (IR) injury, as well as the effects of CGL or CBS inhibition. Furthermore, we elucidated the mechanism underlying the action of H2S in the kidneys. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were randomly assigned to five groups: a sham, renal IR control, sodium hydrosulfide (NaHS) treatment, H2S donor, and CGL or CBS inhibitor administration group. Levels of blood urea nitrogen (BUN), serum creatinine (Cr), renal tissue malondialdehyde (MDA), and superoxide dismutase (SOD) were estimated. Histological changes, apoptosis, and expression of mitogen-activated protein kinase (MAPK) family members (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38) were also evaluated. RESULTS: NaHS attenuated serum BUN and Cr levels, as well as histological damage caused by renal IR injury. Administration of NaHS also reduced oxidative stress as evident from decreased MDA, preserved SOD, and reduced apoptotic cells. Additionally, NaHS prevented renal IR-induced MAPK phosphorylation. The CGL or CBS group showed increased MAPK family activity; however, there was no significant difference in the IR control group. CONCLUSION: Exogenous H2S can mitigate IR injury-led renal damage. The proposed beneficial effect of H2S is, in part, because of the anti-oxidative stress associated with modulation of the MAPK signaling pathways.

Age-Related Changes in Sulfur Amino Acid Metabolism in Male C57BL/6 Mice

Alterations in sulfur amino acid metabolism are associated with an increased risk of a number of common late-life diseases, which raises the possibility that metabolism of sulfur amino acids may change with age. The present study was conducted to understand the age-related changes in hepatic metabolism of sulfur amino acids in 2-, 6-, 18- and 30-month-old male C57BL/6 mice. For this purpose, metabolite profiling of sulfur amino acids from methionine to taurine or glutathione (GSH) was performed. The levels of sulfur amino acids and their metabolites were not significantly different among 2-, 6- and 18-month-old mice, except for plasma GSH and hepatic homocysteine. Plasma total GSH and hepatic total homocysteine levels were significantly higher in 2-month-old mice than those in the other age groups. In contrast, 30-month-old mice exhibited increased hepatic methionine and cysteine, compared with all other groups, but decreased hepatic S-adenosylmethionine (SAM), S-adenosylhomocysteine and homocysteine, relative to 2-month-old mice. No differences in hepatic reduced GSH, GSH disulfide, or taurine were observed. The hepatic changes in homocysteine and cysteine may be attributed to upregulation of cystathionine β-synthase and down-regulation of γ-glutamylcysteine ligase in the aged mice. The elevation of hepatic cysteine levels may be involved in the maintenance of hepatic GSH levels. The opposite changes of methionine and SAM suggest that the regulatory role of SAM in hepatic sulfur amino acid metabolism may be impaired in 30-month-old mice.

DNA damage in homocystinuria: 8-oxo-, 8-dihydro-2'-deoxyguanosine levels in cystathionine-ß-synthase deficient patients and the in vitro protective effect of N-acetyl­L­cysteine

Introduction: Homocysteine (Hcy) tissue accumulation occurs in a metabolic disease characterized biochemically by cystathionine ß-synthase (CBS) deficiency and clinically by mental retardation, vascular problems, and skeletal abnormalities. Previous studies indicate the occurrence of DNA damage secondary to hyperhomocysteinemia and it was observed that DNA damage occurs in leukocytes from CBS-deficient patients. This study aimed to investigate whether an oxidative mechanism could be involved in DNA damage previously found and investigated the in vitro effect of N-acety-L-cysteine (NAC) on DNA damage caused by high Hcy levels. Methods: We evaluated a biomarker of oxidative DNA damage in the urine of CBS­deficient patients, as well as the in vitro effect of NAC on DNA damage caused by high levels of Hcy. Moreover, a biomarker of lipid oxidative damage was also measured in urine of CBS deficient patients. Results: There was an increase in parameters of DNA (8-oxo-7,8-dihydro-2'- deoxyguanosine) and lipid (15-F2t-isoprostanes levels) oxidative damage in CBS-deficient patients when compared to controls. In addition, a significant positive correlation was found between 15-F2t-isoprostanes levels and total Hcy concentrations. Besides, an in vitro protective effect of NAC at concentrations of 1 and 5 mM was observed on DNA damage caused by Hcy 50 µM and 200 µM. Additionally, we showed a decrease in sulfhydryl content in plasma from CBS-deficient patients when compared to controls. Discussion: These results demonstrated that DNA damage occurs by an oxidative mechanism in CBS deficiency together with lipid oxidative damage, highlighting the NAC beneficial action upon DNA oxidative process, contributing with a new treatment perspective of the patients affected by classic homocystinuria.

Classical hemocystinuria in two Filipino patients

Classical hemocystinuria is an inborn error of metabolism caused by a deficiency of cystathionine beta-synthase that converts hemocysteine to cystathionine. This then leads to elevation of hemocysteine which results in abnormalities of the eyes, skeleton, central nervous system and vascular hemocystinuria. Patient 1 presented with lens dislocation and mental retardation while Patient 2 presented with thromboembolism, mental retardation and lens dislocation. The elevated plasma hemocysteine and methionine levels lead to the diagnosis of hemocystinuria.

A Case of Cystathioninuria with Delayed Development

Cystathionine is well-known intermediate in the metabolism of methionine. It is cleaved to cysteine and homoserine by gamma-cystathionase. This enzyme utilize pyridoxal 5'-phosphate as coenzyme. gamma-cystathionase deficiency leads to persistent excretion of large amount of cystathionine in urine, as well as to accumulation of cystathionine in body tissues and fluids. It is inherited as an autosomal recessive trait and shows wide variety of clinical manifestations. No clinical abnormality seems to be specifically associated with gamma-cystathionase deficiency. The majority of patients responded to high dose administration of pyridoxine. We report the first case of cystathioninuric patient in Korea, 19 months of female with developmental delay. In brain MRI, there was generalized mild brain atrophy. There were several times of brief paroxysmal generalized polyspike and wave discharges in electroencephalography(EEG). In amino acid analysis of urine, there was elevated level of cystathionine. She was treated with high dose of pyridoxine. In follow up analysis of urinary amino acid, the cystathionine level was markedly decreased to normal range, and EEG was normalized. Her development shows improvement.

A Case of Homocystinuria with Ectopia Lentis

Homocystinuria is an inborn error on the pathway of the methionine metabolism. It is mainly caused by a cystathionine B-synthase deficiency in the brain or liver. Homocystinuria is biochemically characterized by: 1) an increase of the homocystine and methionine concentration in the plasma; and 2) a decrease of the cystine with an increased excretion of homocystine in the urine. The clinical manifestations of this autosomal recessive disorder include: ectopoia lentis, skeletal abnormalities, high incidence of thromboembolism and high frequency of mental retardation. We have been experiencing a case of a 10 year old female patient who has suffered from homocystinuria. She has undergone mental retardation, poor vision caused by ocular complications and Marfanoid feautures.

Uma causa rara de osteoporose: homocistinúria / A rare cause of osteoporosis: homocystinuria

Os autores apresentam uma rara causa de osteoporose - a homocistinúria. O paciente apresentavva osteoporose generalizada, fratura espontânea e graves complicaçöes vasculares. Säo revistos a patogenia e o quadro clínico a apontadas as sugestöes terapêuticas