Effect of lncRNA WT1-AS regulating WT1 on oxidative stress injury and apoptosis of neurons in Alzheimer's disease via inhibition of the miR-375/SIX4 axis.

OBJECTIVE: To study the effect of lncRNA WT1-AS on oxidative stress injury (OSI) and apoptosis of neurons in Alzheimer's disease (AD) and its specific mechanisms related to the microRNA-375 (miR-375)/SIX4 axis and WT1 expression. RESULTS: After bioinformatic prediction, WT1-AS was found to be downregulated in Aß25-35treated SH-SY5Y cells, and WT1-AS overexpression inhibited WT1 expression. WT1 could target miR-375 to promote its expression. miR-375 bound to SIX4, and miR-375 overexpression inhibited SIX4 expression. WT1-AS inhibited OSI and apoptosis, while WT1 and miR-375 overexpression or SIX4 silencing reversed the WT1-AS effect on OSI and apoptosis. In vivo experiments revealed that WT1-AS improved learning/memory abilities and inhibited OSI and apoptosis in AD mice. CONCLUSION: Overexpression of WT1-AS can inhibit the miR-375/SIX4 axis, OSI and neuronal apoptosis in AD by inhibiting WT1 expression. METHODS: Related lncRNAs were identified, and miR-375 downstream targets were predicted. WT1-AS, WT1, miR-375 and SIX4 expression was detected in a cell model induced by Aß25-35. The binding of WT1 with miR-375 and that of miR-375 with SIX4 were further confirmed. Adenosine triphosphate (ATP), reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and lactate dehydrogenase (LDH) activities, and apoptosis levels were tested after mitochondrial membrane potential observation. Learning/memory abilities and neuronal apoptosis were tested in a mouse model.

SNCA Gene Polymorphism may Contribute to an Increased Risk of Alzheimer's Disease.

BACKGROUND: The purpose of this study is to elucidate the association between α-synuclein (SNCA) polymorphisms and the risk of Alzheimer's disease (AD). METHODS: The PCR-RFLP was applied to detect SNCA gene rs6532190, rs3775430, and rs10516846 polymorphisms in 98 AD patients and 105 healthy elderly. RESULTS: The GG frequency of rs10516846 was evidently increased in AD group than control group (P < 0.05). There was a significant difference in SNCA level between the AD and control groups (P < 0.01). In the AD group, the SNCA level in cerebrospinal fluid of GG (rs10516846) carriers was increased as compared with AA carriers (P < 0.05). The GG (rs10516846) frequency of the early-onset AD group is significantly higher than that of the late-onset AD group (P < 0.05). The frequency of rs3775430 GG was lower in the early-onset group than that in the late-onset group (0% vs. 16.7%). The SNCA level in cerebrospinal fluid of GG (rs10516846) carriers in the early-onset AD group is higher than that of AA carriers (P < 0.05). CONCLUSION: SNCA gene polymorphism may be associated with an increased risk of AD and GG genotype of rs10516846 and elevated SNCA level in CSF may increase the risk of early-onset AD.

ABCB1 gene C3435T polymorphism and drug resistance in epilepsy: evidence based on 8,604 subjects.

BACKGROUND: The present study aimed to assess the role of C3435T polymorphism in drug-resistance in epilepsy by a meta-analysis. MATERIAL AND METHODS: Databases were obtained from the Cochrane Library, MEDLINE, EMBASE, PubMed, Science Direct database, CNKI, and Wanfang up to October 2014. All the case-control association studies evaluating the role of ABCB1 C3435T in pharmacoresistance to anti-epileptic drug (AED) were identified. RevMan 5.0 software was utilized to perform quantitative analyses in an allele model (C vs. T) and a genotype model (CC vs. CT+TT). RESULTS: From the 189 potential studies, we included 28 articles for the meta-analysis, including 30 independent case-control studies involving 4124 drug-resistant epileptic patients and 4480 epileptic patients for whom drug treatment was effective. We excluded 164 studies because of duplication, lack of genotype data, and non-clinical research. We found that C3435T polymorphism was not significantly associated with drug resistance in epilepsy, either in allele model (C vs. T: OR=1.07; 95%CI: 0.95-1.19) or in genotype model (CC vs. CT+TT: OR=1.05; 95%CI: 0.89-1.24, P=0.55). Subgroup analyses suggested that in Caucasian populations there are significant differences between resistance group (NR) and control group (R) in both allele model (C vs. T: OR=1.09; 95%CI: 1.00-1.18, P=0.05) and genotype model (CC vs. CT+TT: OR=1.20; 95%CI: 1.04-1.40, P=0.01). However, we did not find this association in Asian populations. CONCLUSIONS: We conclude that the ABCB1 C3435T polymorphism may be a genetic marker for drug resistance in epilepsy in Caucasian populations.

Fluorocitrate induced the alterations of memory-related proteins and tau hyperphosphorylation in SD rats.

Astrocytes provide structural, metabolic and trophic supports for neurons. However, there are no direct evidences whether astrocytes involve in the regulation of synaptic proteins expression and tau phosphorylation until now. Here, we injected 1 nmol fluorocitrate (FC), which preferentially taken up by astrocytes and results in reversible inhibition of the astrocytic tricarboxylic acid cycle, into the left lateral ventricle of the brain in the SD rats for 1h, and found that FC treatment decreased several memory-related proteins levels, such as AMPA receptor GluR1/2, postsynaptic density protein 93/95, Arc and phosphorylated cAMP response element binding proteins, while increased synaptophysin and synapsin I levels in the hippocampus. FC treatment also increased the levels of phosphorylated tau at multiple Alzheimer-related phosphorylation sites, as well as activation of glycogen synthase kinase-3ß and inactivation of protein phosphatase-2A. Similar effects were also observed in the primary hippocampal neurons, which were cultured with the conditioned media from FC-treatment primary astrocytes. Our data suggest that astrocytes regulate neuronal tau phosphorylation and several synaptic proteins expression.

Fiber Bragg grating-based plane strain monitoring of aerostat envelope structures.

A theoretical analysis of fiber Bragg grating (FBG)-based plane strain monitoring of aerostat envelope structures is presented. Plane strain analysis of FBG-based aerostat envelope structures is much more complex than the case along the axis of the optical fiber because the effect of transverse stress on the FBG should be taken into consideration. To achieve accurate strain measurement of the aerostat envelope, a theoretical model is set up by using two perpendicular fibers in the monitoring. An analytical formula that evaluates the relationship between the strain measured by FBG sensors and the real one in the aerostat envelope is established. On the other hand, the real strain of aerostat envelope strain is affected by two unknown parameters, axial transfer rate K(L) and the radial transfer rate K(R). An equation is derived to calculate the axial transfer rate K(L). Then, the finite element method results show that K(R) is a very small value, but it cannot be ignored in accurate measurement. This paper would lay a theoretical groundwork for the research and design of FBG sensors in the structural health monitoring of aerostat envelope structures.

Analysis of strain transfer of six-layer surface-bonded fiber Bragg gratings.

A theoretical analysis of strain transfer of six-layer surface-bonded fiber Bragg gratings (FBGs) subjected to uniform axial stress is presented. The proposed six-layer structure consists of optical fiber, protective coating, adhesive layer, substrate layer, outer adhesive layer, and host material, which is different from the four-layer case of common acknowledgement. A theoretical formula of strain transfer rate from host material to optical fiber is established to provide an accurate theoretical prediction. On the basis of the theoretical analysis, influence parameters of the middle layers that affect the average strain transfer rate of the six-layer surface-bonded FBG are discussed. After the parametric study, a selection scheme of sensor parameters for numerical validation, which makes the average strain transfer rate approach unity, is determined. Good agreement is observed between numerical results and theoretical predictions. In the end, the six-layer model is extended to the general situation of multiple substrate layers, which lays a theoretical groundwork for the research and design of surface-bonded FBGs with substrate layers in the future.

Robust guaranteed cost control for singular Markovian jump systems with time-varying delay.

This paper is concerned with the guaranteed cost control for continuous-time singular Markovian jump systems with time-varying delay. Without using the free weighting matrices method, a delay-range-dependent condition is derived in terms of strict linear matrix inequality (LMI), which guarantees that the singular system is regular, impulse free and mean-square exponentially stable with an H(∞) performance. Based on this, the existence condition of the guaranteed cost state feedback controller is proposed. A numerical example is given to illustrate the effectiveness and less conservatism of the proposed design method.

Injection of bradykinin or cyclosporine A to hippocampus induces Alzheimer-like phosphorylation of Tau and abnormal behavior in rats.

OBJECTIVE: To reconstitute an Alzheimer's disease model by administering bradykinin (BK) or cyclosporine A (CSA) to the rat hippocampus. METHODS: BK or CSA was administered to the rat hippocampus using a stereotaxic apparatus. The behavior of the rats was observed with an electronic attack jump platform. The phosphorylation of Tau protein was examined through immunohistochemical assay. RESULTS: Behavior studies showed that an obvious disturbance in learning and memory was seen in BK injected rats.No obvious dysfunction was observed in CSA injected rats. The results obtained by immunohistochemical assay indicated that the staining of M4, 12E8, paired helical filament-1 (PHF-1) and calcium/calmodulin-dependent protein kinase II (CaMKII) was stronger, and that of Tau-1 was weaker in BK injected rats compared with the control group. We also found that the binding of M4 and PHF-1 but not 12E8 to Tau was significantly increased in CSA injected rats. As for BK injection, binding of Tau-1 to Tau was decreased after CSA injection. CONCLUSION: To our knowledge, this is the first data showing in vivo that the activation of CaMKII induces both Alzheimer-like Tau phosphorylation and behavioral disturbances.