Anti-oxidative stress and cognitive improvement of a semi-synthetic isoorientin-based GSK-3ß inhibitor in rat pheochromocytoma cell PC12 and scopolamine-induced AD model mice via AKT/GSK-3ß/Nrf2 pathway.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive deficits. Although the pathogenesis of AD is unclear, oxidative stress has been implicated to play a dominant role in its development. The flavonoid isoorientin (ISO) and its synthetic derivatives TFGF-18 selectively inhibit glycogen synthase kinase-3ß (GSK-3ß), a potential target of AD treatment. PURPOSE: To investigate the neuroprotective effect of TFGF-18 against oxidative stress via the GSK-3ß pathway in hydrogen peroxide (H2O2)-induced rat pheochromocytoma PC12 cells in vitro and scopolamine (SCOP)-induced AD mice in vivo. METHOD: The oxidative stress of PC12 cells was induced by H2O2 (600 µM) and the effects of TFGF-18 (2 and 8 µM) or ISO (12.5 and 50 µM) were observed. The AD mouse model was induced by SCOP (3 mg/kg), and the effects of TFGF-18 (2 and 8 mg/kg), ISO (50 mg/kg), and donepezil (DNP) (3 mg/kg) were observed. DNP, a currently accepted drug for AD was used as a positive control. The neuronal cell damages were analyzed by flow cytometry, LDH assay, JC-1 assay and Nissl staining. The oxidative stress was evaluated by the detection of MDA, SOD, GPx and ROS. The level of ACh, and the activity of AChE, ChAT were detected by the assay kit. The expressions of Bax, Bcl-2, caspase3, cleaved-caspase3, p-AKT (Thr308), AKT, p-GSK-3ß (Ser9), GSK-3ß, Nrf2, and HO-1, as well as p-CREB (Ser133), CREB, and BDNF were analyzed by western blotting. Morris water maze test was performed to analyze learning and memory ability. RESULTS: TFGF-18 inhibited neuronal damage and the expressions of Bax caspase3 and cleaved-caspase3, and increased the expression of Bcl-2 in vitro and in vivo. The level of MDA and ROS were decreased while the activities of SOD and GPx were increased by TFGF-18. Moreover, TFGF-18 increased the p-AKT, p-GSK-3ß (Ser9), Nrf2, HO-1, p-CREB, and BDNF expression reduced by H2O2 and SCOP. Meanwhile, MK2206, an AKT inhibitor, reversed the effect of TFGF-18 on the AKT/GSK-3ß pathway. In addition, the cholinergic system (ACh， ChAT, and AChE) disorders were retrained and the learning and memory impairments were prevented by TFGF-18 in SCOP-induced AD mice. CONCLUSIONS: TFGF-18 protects against neuronal cell damage and cognitive impairment by inhibiting oxidative stress via AKT/GSK-3ß/Nrf2 pathway.

LncRNA MSC-AS1 Promotes Colorectal Cancer Progression by Regulating miR-325/TRIM14 Axis.

BACKGROUND: LncRNA MSC-AS1 has been reported to be a tumor promoter in hepatocellular carcinoma. However, the function of MSC-AS1 in colorectal cancer (CRC) has not been elucidated. It is designed to study the expression level of MSC-AS1 and investigate its biological effect on the progression of CRC. METHODS: The expression patterns of MSC-AS1, miR-325, and TRIM14 were explored by RT-qPCR in CRC tissues and cells. The protein expression of TRIM14 was tested by Western blot assay. The association between MSC-AS1 expression and clinicopathological data was analyzed by chi-squared test. CCK-8 assay, colony formation, and Transwell assay were used to investigate the effect of MSC-AS1 on cell growth, invasion, and migration in CRC cells. The correlations among MSC-AS1, miR-325, and TRIM14 were analyzed by Pearson's correlation coefficient analysis. RESULTS: We found that MSC-AS1 and TRIM14 were upregulated in CRC tissues, while miR-325 was downregulated in CRC tissues. Functional experiments demonstrated that MSC-AS1 knockdown inhibited cell proliferation, migration, and invasion abilities in CRC cells. Additionally, miR-325 was proved to be a target miRNA of MSC-AS1, and TRIM14 might be a downstream gene of miR-325. Besides that, MSC-AS1 counteracted the inhibitory effect of miR-325 on the cell progression and TRIM14 expression. CONCLUSION: Our results indicated that MSC-AS1 facilitated CRC progression by sponging miR-325 to upregulate TRIM14 expression. We suggested that MSC-AS1 might be a potential lncRNA-target for CRC therapy.

Step angles to reduce the north-finding error caused by rate random walk with fiber optic gyroscope.

We study the relationship between the step angles and the accuracy of north finding with fiber optic gyroscopes. A north-finding method with optimized step angles is proposed to reduce the errors caused by rate random walk (RRW). Based on this method, the errors caused by both angle random walk and RRW are reduced by increasing the number of positions. For when the number of positions is even, we proposed a north-finding method with symmetric step angles that can reduce the error caused by RRW and is not affected by the azimuth angles. Experimental results show that, compared with the traditional north-finding method, the proposed methods with the optimized step angles and the symmetric step angles can reduce the north-finding errors by 67.5% and 62.5%, respectively. The method with symmetric step angles is not affected by the azimuth angles and can offer consistent high accuracy for any azimuth angles.

Enhanced multiposition method to suppress the north finding error caused by bias drift with fiber optic gyroscopes.

We present an enhanced multiposition method (EMM) to suppress the north finding error caused by bias drift with fiber optic gyroscopes (FOGs). The new proposal is a static method to find the true north, and it employs a differential strategy and a rotation scheme of increasing step angle. Using the noise model of Allan variance, we analyze the north finding errors caused by angle random walk (ARW), rate random walk (RRW), and rate ramp (RR) theoretically, where RRW and RR are two main noise sources of bias drift, and ARW is the rate white noise. Theoretical analysis indicates that, in the traditional multiposition method (TMM), as the position number increases, the error caused by ARW decreases while that by bias drift increases. Therefore, the suppressions of ARW and bias drift are conflicted with each other. The north finding accuracy is limited by bias drift. In contrast, in EMM, both errors caused by ARW and bias drift will decrease as the position number increases. Experimental results with two specific FOGs verify our theoretical analysis. In our experiments, we study the effect of position number and step angle on the north finding accuracy. Utilizing the proposed EMM, for FOG-1, the north finding error has been reduced by 76.60%, and for FOG-2, a 36.33% reduction has been achieved. Our proposal provides a more effective and stable way to find true north, and it can also be applied to other rate gyroscopes.

Method for suppressing the bias drift of interferometric all-fiber optic gyroscopes.

We propose a simple and, to our knowledge, novel method for suppressing the bias drift of interferometric all-fiber optic gyroscopes (I-FOGs) and for self-calibrating the bias of I-FOGs to zero. Using a square wave to reverse the polarity of the sinusoidal voltage on a piezoelectric (PZT) modulator periodically, and calculating the output signal of a demodulator circuit in-phase with the square wave by a digital signal processor (DSP), we successfully reduce the bias drift of I-FOGs. Experimental results show that, at room temperature, the proposed method dramatically reduces the bias instability of an I-FOG from 0.201 deg/h to 0.102 deg/h. With this method, the I-FOGs no longer need zero calibration.