Objective: The main pathological change of Parkinson’s disease (PD) is progressive degeneration and necrosis of dopaminergic neurons in the midbrain, forming a Lewy body in many of the remaining neurons. Studies have found that in transgenic Drosophila, mutations in the PTEN-inducible kinase 1 (PINK1) gene may cause indirect flight muscle defects in Drosophila, and mitochondrial structural dysfunction as well.
Methods: In this study, Wnt4 gene overexpression and knockdown were performed in PINK1 mutant PD transgenic Drosophila, and the protective effect of Wnt4 gene on PD transgenic Drosophila and its possible mechanism were explored. The Wnt4 gene was screened in the previous experiment; And by using the PD transgenic Drosophila model of the MHC-Gal4/UAS system, the PINK1 gene could be specifically activated in the Drosophila muscle tissue.
Results: In PINK1 mutation transgenic fruit flies, the Wnt4 gene to study its implication on PD transgenic fruit flies’ wing normality and flight ability. We found that overexpression of Wnt4 gene significantly reduced abnormality rate of PD transgenic Drosophila and improved its flight ability, and then, increased ATP concentration, enhanced mitochondrial membrane potential and normalized mitochondrial morphology were found. All of these findings suggested Wnt4 gene may have a protective effect on PD transgenic fruit flies. Furthermore, in Wnt4 gene overexpression PD transgenic Drosophila, down-regulation autophagy and apoptosis-related proteins Ref(2)P, Pro-Caspase3, and up-regulation of Beclin1, Atg8a, Bcl2 protein were confirmed by Western Blotting.
Conclusion: The results imply that the restoring of mitochondrial function though Wnt4 gene overexpression in the PINK1 mutant transgenic Drosophila may be related to autophagy and/or apoptosis. 相似文献
Increasing costs of research and development in the pharmaceutical industry has necessitated a growing interest in the early prediction of human pharmacokinetics of drug candidates. Of growing interest is the need to understand oral absorption, the most common route of small molecule drug administration. The fraction of dose absorbed (%Fa) is considered a critical yet challenging parameter to predict. A kinetic model has been developed and tested to provide an early prediction of the fraction dose absorbed in humans. Unlike the traditional plug-flow model, this model assumes first-order kinetics to estimate the amount of drug present in the stomach and small intestine as a function of time and calculates the amount of drug released and absorbed during the transit. Other variables can be included in calculation as a function of time to better mimic the physiological condition with this approach. Absorption efficiency is assigned along with %Fa to give a quantitative estimate of the limiting factor for oral absorption. The model was tested with literature and in-house compounds. It was found that this model gives a good prediction of human %Fa with a correction coefficient (R2) of 0.8 and greater between predicted and reported %Fa for all compounds. 相似文献
Aims: To investigate the value of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in a cohort of a community’s residents who were diagnosed as pre-diabetes, and to evaluate the association of VAT and SAT with insulin resistance.Methods: This study was based on cross-sectional analysis of data from 107 adults. VAT and SAT were assessed by computed tomography. Insulin resistance was defined by homeostasis model assessment of insulin resistance >2.69. The relationship of VAT and SAT with insulin resistance were examined by linear regression. Logistic regression was used to analyze the association of VAT and SAT with insulin resistance.Results: A total of 87 subjects had VAT ≥100?cm2. Thirty-six out of 107 (33.6%) subjects were detected to have insulin resistance, 71 were normal (66.4%), and all had insulin resistance with VAT ≥100?cm2. VAT (r?=?0.378, p?.001) and SAT (r?=?0.357, p?.001) were significantly and positively correlated with insulin resistance. In multiple regression analysis when VAT and SAT were simultaneously included after adjustment for age, gender, BMI, and WC, the association between VAT and insulin resistance was still maintained (p?=?.003), but that of SAT was lost.Conclusion: Pre-diabetic subjects with insulin resistance had elevated levels of VAT. VAT was more strongly associated with insulin resistance than SAT in Chinese subjects with pre-diabetes. 相似文献
Parasitology Research - In our previous study, we obtained a large number of differentially expressed genes (DEGs) between second-generation merozoites (MZ-2) and third-generation merozoites (MZ-3)... 相似文献
Inflammation Research - Efficient production of monocytic myeloid-derived suppressor cells (M-MDSCs) with stable immunosuppressive function is crucial for immunomodulatory cell therapy for many... 相似文献