ABSTRACT
Background@#At the therapeutic doses, diclofenac sodium (DFS) has few toxic side effects on mammals. On the other hand, DFS exhibits potent toxicity against birds and the mechanisms remain ambiguous. @*Objectives@#This paper was designed to probe the toxicity of DFS exposure on the hepatic proteome of broiler chickens. @*Methods@#Twenty 30-day-old broiler chickens were randomized evenly into two groups (n = 10).DFS was administered orally at 10 mg/kg body weight in group A, while the chickens in group B were perfused with saline as a control. Histopathological observations, serum biochemical examinations, and quantitative real-time polymerase chain reaction were performed to assess the liver injury induced by DFS. Proteomics analysis of the liver samples was conducted using isobaric tags for relative and absolute quantification (iTRAQ) technology. @*Results@#Ultimately, 201 differentially expressed proteins (DEPs) were obtained, of which 47 were up regulated, and 154 were down regulated. The Gene Ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to screen target DEPs associated with DFS hepatotoxicity. The regulatory relationships between DEPs and signaling pathways were embodied via a protein-protein interaction network. The results showed that the DEPs enriched in multiple pathways, which might be related to the hepatotoxicity of DFS, were “protein processing in endoplasmic reticulum,” “retinol metabolism,” and “glycine, serine, and threonine metabolism.” @*Conclusions@#The hepatotoxicity of DFS on broiler chickens might be achieved by inducing the apoptosis of hepatocytes and affecting the metabolism of retinol and purine. The present study could provide molecular insights into the hepatotoxicity of DFS on broiler chickens.
ABSTRACT
AIM: To promote the Clinical Data Inter-change Standards Consortium (CDISC) standard in clinical trials and promote the standardization of clinical trial data. METHODS: To combine the implementation guide of Analysis Data Model (ADaM) and common problems of actual data, and to introduce the application of analytical data model ADaM in the safety of bioequivalence trails of generic drugs. RESULTS: For different types of clinical trial data, according to various situations that may occur, a safety analysis data set that meets the standards was generated. CONCLUSION: Under the background of the continuous development of generic drugs in China and the low degree of standardization of clinical trial data, the use of CDISC standards in clinical research can promote the standardization of clinical trial data, and can also shorten the time of statistical analysis and accelerate the process of drug development.
ABSTRACT
Objective To detect serum oxytocin and highly sensitive C-reactive protein (hs-CRP) levels in obese and type 2 diabetes mellitus(T2DM) subjects and investigate the relationships between serum oxytocin levels and hs-CRP, glycolipid metabolism, insulin resistance and pancreas β cell function. Methods A total of 176 subjects were enrolled in the study, including 88 patients with newly-diagnosed type 2 diabetes ( T2DM) and 88 subjects with normal glucose tolerance(NGT). NGT and T2DM groups were further divided each into normal weight (NW) and obese(OB) subgroups. Obesity was defined as body mass index(BMI)≥25 kg/ m2 according to the WHO-Western Pacific Region diagnostic criteria (2000). 75g oral glucose tolerance test ( OGTT) was performed in all subjects. Fasting plasma glucose ( FPG), 2 h postprandial plasma glucose (2hPG), fasting insulin ( FINS), 2h postprandial serum insulin(2hINS), HbA1C and lipids were also determined. Insulin resistance and pancreas β-cell function were determined by homeostasis model assessment ( HOMA-IR, HOMA-β). Highly sensitive C-reactive protein(hs-CRP) level was determined by chemiluminescence immunoassay and fasting serum oxytocin level was determined by ELISA. Results Serum oxytocin level was lower in T2DM group than that in NGT group(P<0. 01), while serum hs-CRP level was higher in T2DM group than that in NGT group(P<0. 01). The level of serum oxytocin in subjects with obesity was also lower than that in subjects with NW in both NGT and T2DM groups [7. 16(6. 45-8. 82) vs 7. 98(7. 03-9. 17) ng/ L and 9. 23(8. 16-10. 36) vs 9. 86(8. 77-12. 06) ng/ L, P<0. 05]. The level of serum hs-CRP in subjects with obesity was higher than that in subjects with NW in both NGT and T2DM groups [0. 99(0. 25-1. 97) vs 0. 54(0. 19-0. 91) mg/ L and 3. 47(1. 63-6. 20) vs 1. 65(0. 81-3. 81) mg/ L, P<0. 05]. Serum oxytocin level was negatively correlated with hs-CRP, BMI, WC, WHR, HbA1C , FPG, 2hPG, FINS, 2hINS, total cholesterol, triglycerides, LDL-C and HOMA-IR, while was positively correlated with HOMA-β(P<0. 05). Subjects within the upper serum hs-CRP tertile had lower level of oxytocin when compared to subjects in the middle or lower serum hs-CRP tertiles(P<0. 05 ). Conclusion Serum oxytocin level was decreased in subjects with type 2 diabetes as well as with obesity. Serum oxytocin level was closely correlated with inflammation, glycolipid metabolism, insulin resistance, and pancreas β cell function. It may play an important role in the pathogenesis of obesity and T2DM.