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
Daily exposure to sunlight is known to affect the structure and function of the epidermal basement membrane (BM), as well as epidermal differentiation and epidermal barrier function. The aim of this study is to clarify whether the inhibition of BM‐degrading enzymes such as heparanase and matrix metalloproteinase 9 (MMP‐9) can improve the epidermal barrier function of facial skin, which is exposed to the sun on a daily basis. 1‐(2‐hydroxyethyl)‐2‐imidazolidinone (HEI) was synthesized as an inhibitor of both heparanase and MMP‐9. HEI inhibited not only the BM damage at the DEJ but also epidermal proliferation, differentiation, water contents and transepidermal water loss abnormalities resulting from ultraviolet B (UVB). This was determined in this study by the use of UVB‐induced human cultured skins as compared with the control without HEI. Moreover, topical application of HEI improved epidermal barrier function by increasing water content and decreasing transepidermal water loss in daily sun‐exposed facial skin as compared with non‐treated skins. These results suggest that the inhibition of both heparanase and MMP‐9 is an effective way to care for regularly sun‐exposed facial skin by protecting the BM from damage. 相似文献
Marginal rate-based analyses are widely used for the analysis of recurrent events in clinical trials. In many areas of application, the events are not instantaneous but rather signal the onset of a symptomatic episode representing a recurrent infection, respiratory exacerbation, or bout of acute depression. In rate-based analyses, it is unclear how to best handle the time during which individuals are experiencing symptoms and hence are not at risk. We derive the limiting value of the Nelson-Aalen estimator and estimators of the regression coefficients under a semiparametric rate-based model in terms of an underlying two-state process. We investigate the impact of the distribution of the episode durations, heterogeneity, and dependence on the asymptotic and finite sample properties of standard estimators. We also consider the impact of these features on power in trials designed to test intervention effects on rate functions. An application to a trial of individuals with herpes simplex virus is given for illustration. 相似文献
Introduction: In early childhood, wheezing due to lower respiratory tract illness is often associated with infection by commonly known respiratory viruses such as respiratory syncytial virus (RSV) and human rhinovirus (RV). How respiratory viral infections lead to wheeze and/or asthma is an area of active research.
Areas covered: This review provides an updated summary of the published information on the development of post-viral induced atopy and asthma and the mechanisms involved. We focus on the contribution of animal models in identifying pathways that may contribute to atopy and asthma following respiratory virus infection, different polymorphisms that have been associated with asthma development, and current options for disease management and potential future interventions.
Expert commentary: Currently there are no prophylactic therapies that prevent infants infected with respiratory viruses from developing asthma or atopy. Neither are there curative therapies for patients with asthma. Therefore, a better understanding of genetic factors and other associated biomarkers in respiratory viral induced pathogenesis is important for developing effective personalized therapies. 相似文献
ObjectiveFunctional processes in the brain are segregated in both the spatial and spectral domain. Motivated by findings reported at the cortical level in healthy participants we test the hypothesis in the basal ganglia of Parkinson’s disease patients that lower frequency beta band activity relates to motor circuits associated with the upper limb and higher beta frequencies with lower limb movements.MethodsWe recorded local field potentials (LFPs) from the subthalamic nucleus using segmented “directional” DBS leads, during which patients performed repetitive upper and lower limb movements. Movement-related spectral changes in the beta and gamma frequency-ranges and their spatial distributions were compared between limbs.ResultsWe found that the beta desynchronization during leg movements is characterised by a strikingly greater involvement of higher beta frequencies (24–31 Hz), regardless of whether this was contralateral or ipsilateral to the limb moved. The spatial distribution of limb-specific movement-related changes was evident at higher gamma frequencies.ConclusionLimb processing in the basal ganglia is differentially organised in the spectral and spatial domain and can be captured by directional DBS leads.SignificanceThese findings may help to refine the use of the subthalamic LFPs as a control signal for adaptive DBS and neuroprosthetic devices. 相似文献