Metabolomics analysis to interpret changes in physiological and metabolic responses to chronic heat stress in Pekin ducks.

Heat stress (HS) is a major environmental threat that affects duck production in subtropical and tropical regions, especially in summer. This study aimed to evaluate the physiological and metabolic responses of Pekin ducks to chronic HS conditions via liquid chromatography-mass spectrometry (LC-MS) using a paired-fed (PF) experimental design. On the basis of equivalent feed intake (HS vs. PF), HS significantly reduced growth performance and the percentage of leg and breast muscles, however, markedly increased the percentage of abdominal fat and breast skin fat. Serum metabolomics results revealed that heat-stressed ducks showed enhanced glycolysis and pentose phosphate pathways, as demonstrated by higher glucose 6-phosphate and 6-phogluconic acid levels in the PF vs. HS comparison. HS decreased hepatic mRNA levels of mitochondrial fatty acid ß-oxidation-related genes (MCAD and SCAD) compared to the PF group, resulting in acetylcarnitine accumulation in serum. Moreover, HS elevated the concentrations of serum amino acids and mRNA levels of ubiquitination-related genes (MuRF1 and MAFbx) in the skeletal muscle and amino acid transporter-related genes (SLC1A1 and SLC7A1) and gluconeogenesis-related genes (PCK1 and PCase) in the liver compared to the PF group. When compared to the normal control group (NC), HS further decreased growth performance, but it elevated the abdominal fat rate. However, increased mRNA levels of ubiquitination-related genes and serum amino acid accumulation were not observed in the HS group compared to the NC group, implying that reduced feed intake masked the effect of HS on skeletal muscle breakdown and is a form of protection for the organism. These results suggest that chronic HS induces protein degradation in the skeletal muscle to provide amino acids for hepatic gluconeogenesis to provide sufficient energy, as Pekin ducks under HS conditions failed to efficiently oxidise fatty acids and ketones in the mitochondria, leading to poor growth performance and slaughter characteristics.

Evaluation of CD98 light chain-LAT1 as a potential marker of cancer stem-like cells in glioblastoma.

OBJECTIVE: Glioma stem cells (GSCs) are a minority population of glioma cells that regarded as the cause of tumor formation and recurrence. Identifying new molecular strategies targeting GSCs must be urgently developed to treat glioblastoma. In this study, one of CD98 light chain-L type amino acid transporter 1 (LAT1) was found as a potential GSC marker. LAT1 served as EAA transporter has been shown to be closely related with tumor invasion, metastasis, angiogenesis, and radiosensitivity. METHODS: LAT1+ and LAT1- glioma cells were sorted by flow cytometry. Cellular immunofluorescence, sphere-formation arrays, and in vitro limiting dilution experiments were used to identify cell stemness. Differentiated glioma stem cells were cultured, and the expressions of ß-tubulinIII, GFAP, and LAT1 were detected by Western blot. Nude mouse models were constructed to observe tumor formation and metastasis in nude mice. RESULTS: LAT1+ glioma cells were testified a small percentage of all cells and selected as the subsequent sorting marker. LAT1+ cells were separated from U87 and U251 cells could express high level of stem cell markers, and possessed GSC properties including self-renewal ability and multi-directional differentiation potential. But LAT1- cells did not have these characteristics. In addition, LAT1+ cells were able to generate tumors in vivo, tumor size of LAT1+ cells formed were much bigger than that of LAT1- cells. CONCLUSION: Our study, including molecular, cell, vitro and vivo experiments, has shown that LAT1+ cells possess GSC properties, and present for the first time that LAT1 can be used as a new marker for GSCs screening.

[Theophylline in the treatment of chronic obstructive pulmonary disease: a randomized, double-blind, placebo-controlled study].

OBJECTIVE: To observe the benefits and safety of low-dose, slow-release oral theophylline for long-term treatment of stable chronic obstructive pulmonary disease (COPD). METHODS: This was a randomized, parallel-group, double-blind, placebo-controlled trial. Slow-release theophylline (200 mg/d) twice daily or placebo (matching theophylline) was randomly given to 110 patients with stable COPD in the rural area of Shaoguan, Guangdong Province, for one year. Efficacy measures were spirometry and exacerbations, quality of life, dyspnea scores, satisfaction with treatments and adverse effects. Comparison of benefits was performed using superiority test. RESULTS: Of 110 patients, 85 (42 subjects in theophylline group and 43 subjects in placebo group) completed the study. An analysis for intention-to-treat (ITT) individuals showed that individuals with the treatment of theophylline experienced statistically fewer numbers [(0.8 +/- 1.2) times/year, (1.7 +/- 2.6) times/year, Z = -1.674, P = 0.047] and days of exacerbations [(4.6 +/- 7.9) d, (12.5 +/- 22.8) d, Z = -1.699, P = 0.045] in comparison to subjects receiving placebo, that patients receiving theophylline were less likely than the placebo group to experience moderate exacerbations [(0.4 +/- 1.0) times/year, (1.0 +/- 1.8) times/year, Z = -2.136, P = 0.017], and that more individuals satisfied with treatments in the theophylline group than the placebo group (n = 16, 3, Z = -2.198, P = 0.014), and that statistically greater improvement in pre-bronchodilators FEV(1) [(0.006 +/- 0.180) L, (-0.053 +/- 0.169) L, t = 1.789, P = 0.038] were found in the theophylline group in comparison to the placebo group. The similar results were observed in an analysis for per-protocol (PP) subjects. Statistical improvement on quality of life was observed in the PP subjects of theophylline group than in placebo group (-28 +/- 20, -20 +/- 23, F = 2.893, P = 0.047). Time to the first exacerbation in patients receiving theophylline was also delayed in comparison to placebo (365 d, 276 d, chi(2) = 3.880, P = 0.049). But no statistical difference was found between the two groups in post-bronchodilators FEV(1) in both ITT and PP subjects (t = -0.012, P = 0.495 and t = 0.040, P = 0.484 respectively). Drug-related adverse events (8.8%) such as insomnia, palpitation, stomach discomforts or stomachache, and headache were observed in the theophylline group. CONCLUSION: Slow-released oral theophylline (200 mg/d) may be beneficial and safe in long-term treatment of stable COPD in rural area.

[Study on the prevalence rate of chronic obstructive pulmonary disease in northern part of Guangdong province].

OBJECTIVE: To investigate the prevalence of chronic obstructive pulmonary disease (COPD) and its risk factors in population over 40 years old in northern part of Guangdong province. METHODS: Using uniform scheme, procedures and questionnaire, a cluster-randomized-sampling survey for the population aged over 40 years in a rural area of Shaoguan in the northern part of Guangdong province was performed. Spirometry was performed for every participant, followed by a bronchodilatation test when bronchial obstruction was present. RESULTS: There were 1468 cases with complete data from 1498 people aged >or= 40 years including 640 males, 828 females with an average age of 54.3 years old. The total prevalence of COPD was 12.0%. The prevalence of COPD in males was significantly higher than that in females (18.3% vs. 7.1%, P < 0.01). Only 80.7% of the patients with COPD presented one or more symptoms as cough, phlegm, or dyspnoea. Underdiagnosis of COPD would be quite serious. Only 26.1% of the cases was previously diagnosed to have chronic bronchitis, emphysema, or COPD. Smoking was an important risk factor to COPD and 78.4% of the patients with COPD were smokers. However, relation of biomass and COPD called for further investigation. CONCLUSION: Prevalence of COPD was much higher than expected in the northern part of Guangdong while smoking was an most important risk factor of COPD. Lung function test seemed to be of great importance to COPD diagnosis, especially in the earlier period of COPD.