Honokiol Exerts Antidepressant Effects in Rats Exposed to Chronic Unpredictable Mild Stress by Regulating Brain Derived Neurotrophic Factor Level and Hypothalamus-Pituitary-Adrenal Axis Activity.

Honokiol (HNK), the main active component of Magnolia officinalis, has shown a variety of pharmacological activities. In the present study, we measured the antidepressant-like effects of HNK in a rat model of chronic unpredictable mild stress (CUMS) and explored its possible mechanisms. The antidepressant-like effects of HNK were assessed in rats by an open field test (OFT), sucrose preference test (SPT) and forced swimming test (FST). Then, serum levels of corticotrophin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) and hippocampal brain-derived neurotrophic factor (BDNF) and glucocorticoid receptor α (GRα) levels were assessed to explore the possible mechanisms. We identified that HNK treatment (2, 4, and 8 mg/kg) alleviated the CUMS-induced behavioural deficits. Treatment with HNK also normalized the CUMS-induced hyperactivity of the limbic hypothalamic-pituitary-adrenal (HPA) axis, as indicated by reduced CRH, ACTH and CORT serum levels. In addition, HNK increased the expression of GRα (mRNA and protein) and BDNF (mRNA and protein) in the hippocampus. These data confirmed the antidepressant-like effects of HNK, which may be related to its normalizing the function of the HPA axis and increasing the BDNF level in the hippocampus.

Inhibition of phosphodiesterase-4 reverses the cognitive dysfunction and oxidative stress induced by Aß25-35 in rats.

Phosphodiesterase-4 (PDE4) inhibitors prevent the breakdown of the second messenger cAMP and have been demonstrated to improve learning in several animal models of cognition. In this study, we explored the antioxidative effects of rolipram in Alzheimer's disease (AD) by using bilateral Aß25-35 injection into the hippocampus of rats, which were used as an AD model. Rats received 3 intraperitoneal (i.p.) doses of rolipram (0.1, 0.5 and 1.25 mg/kg) daily after the injection of Aß25-35 for 25 days. Chronic administration of rolipram prevented the memory impairments induced by Aß25-35, as assessed using the passive avoidance test and the Morris water maze test. Furthermore, rolipram significantly reduced the oxidative stress induced by Aß25-35, as evidenced by the decrease in the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and restored the reduced GSH levels and superoxide dismutase (SOD) activity. Moreover, western blotting and real-time reverse transcription polymerase chain reaction (RT-PCR) analysis showed that rolipram remarkably upregulated thioredoxin (Trx) and inhibited the inducible nitric oxide synthase/nitric oxide (iNOS/NO) pathway in the hippocampus. These results demonstrated that rolipram improved the learning and memory abilities in an Aß25-35-induced AD rat model. The mechanism underlying these effects may be due to the noticeable antioxidative effects of rolipram.

Cognitive improvement of compound danshen in an Aß25-35 peptide-induced rat model of Alzheimer's disease.

BACKGROUND: Senile dementia mainly includes Alzheimer' s disease (AD) and vascular dementia (VD). AD is a progressive and irreversible neurodegenerative disorder that is accompanied with a great deal of social burden. The aim of this study was to investigate the effect of Compound Danshen (CDS) on learning and memory of alzheimer's disease (AD) rat model, as well as to explore the possible connection between CDS and the associated molecules of amyloid beta (Aß). METHODS: Rats were injected with Aß25-35 peptide intracerebroventricularly and CDS were subsequently administered once daily for 23 days. Rats' behavior was monitored using Morris water maze and passive avoidance. Real time PCR and Western blotting were used in determining amyloid precursor protein (APP), ß-site APP cleaved enzyme-1(BACE1), Presenilin-1 (PS1), Insulin-degrading enzyme (IDE) and neprilysin (NEP) in hippocampus. RESULTS: The AD model group presented with spatial learning and memory impairments. CDS and donepezil administration significantly ameliorated the Aß25-35 peptide-induced memory impairment in both Morris water maze (P < 0.05) and passive avoidance task (P < 0.01) compared to the AD model group. Real time PCR results suggested that CDS significantly decreased APP mRNA, PS1 mRNA and increased IDE and NEP mRNA levels. Western blotting analyses showed that CDS decreased the protein expression of APP and PS1 and increased IDE expression. CONCLUSION: CDS improved spatial learning and memory by down-regulating APP, PS1 levels and up-regulating IDE. In future, CDS may have significant therapeutic potential in the treatment of AD patients.

Hierarchical Nb@NbN core-shell-like nanocolumns for asymmetric supercapacitors.

Transition metal nitrides (TMNs) are promising electrode materials for supercapacitors because of their high electrical conductivity and chemical stability. The rational design and facile synthesis of TMNs electrode materials with a unique nanostructure are the key to develop high-performance supercapacitors. Herein, we propose a two-step, binder-free, and eco-friendly approach utilizing magnetron sputtering at an oblique angle deposition configuration to fabricate hierarchical Nb@NbN core-shell-like nanocolumns for supercapacitors. This distinctive heterostructure not only creates lattice defects, increases active surface area, facilitates ion diffusion and charge transfer, but also optimizes the electronic structure and enhances the conductivity. As a result, the hierarchical Nb@NbN core-shell-like nanocolumn electrodes exhibit a high areal capacitance of 53.3 mF cm-2 at 1 mA cm-2 and an excellent capacitance retention of 93.5 % after 20,000 cycles, outperforming pristine NbN and the majority of previously reported TMNs electrodes. Moreover, the assembled Nb@NbN nanocolumns//VN thin films asymmetric supercapacitor device can deliver a maximum energy density of 49.8 mWh cm-3 and power density of 82 W cm-3. This work presents a facile and environmentally friendly strategy for the synthesis of TMNs core-shell-like nanocolumns, and further demonstrates their promising potential for use in supercapacitors.

Sputtered binder-free Cu3N electrode materials for high-performance quasi-solid-state asymmetric supercapacitors.

Developing high-efficiency electrode materials is of great importance in manufacturing supercapacitor devices with superior electrochemical performance. Herein, we for the first time report a binder-free method for controllable growth of Cu3N electrode materials via magnetron sputtering for supercapacitor applications. Benefiting from their unique polyhedral structure and good electrical conductivity, Cu3N electrodes can achieve an areal capacity of 90.7 mC cm-2 at 1 mA cm-2 and outstanding cycling stability with a capacity retention of 97.4% after 20 000 cycles. In particular, the assembled Cu3N//active carbon quasi-solid-state asymmetric supercapacitor can exhibit a maximum energy density of 13.2 µW h cm-2 and a power density of 4.8 mW cm-2 with an operating voltage of 1.6 V. These remarkable performances demonstrate the great potential of sputtered Cu3N electrode materials for future energy storage applications.

FFPM, a PDE4 inhibitor, reverses learning and memory deficits in APP/PS1 transgenic mice via cAMP/PKA/CREB signaling and anti-inflammatory effects.

Thus far, phosphodiesterase-4 (PDE4) inhibitors have not been approved for application in Alzheimer's disease (AD) in a clinical setting due to severe side effects, such as nausea and vomiting. In this study, we investigated the effect of FFPM, a novel PDE4 inhibitor, on learning and memory abilities, as well as the underlying mechanism in the APP/PS1 mouse model of AD. Pharmacokinetic studies have revealed that FFPM efficiently permeates into the brain, and reached peak values in plasma 2 h after orally dosing. A 3-week treatment with FFPM, at doses of 0.25 mg/kg and 0.5 mg/kg, significantly improved the learning and memory abilities of APP/PS1 transgenic mice in the Morris water maze and the Step-down passive avoidance task. Interestingly, we found that while rolipram (0.5 mg/kg) reduced the duration of the α2 adrenergic receptor-mediated anesthesia induced by xylazine/ketamine, FFPM (0.5 mg/kg) or the vehicle did not have an evident effect. FFPM increased the cAMP, PKA and CREB phosphorylation and BDNF levels, and reduced the NF-κB p65, iNOS, TNF-α and IL-1ß levels in the hippocampi of APP/PS1 trangenic mice, as observed by ELISA and Western blot analysis. Taken together, our data demonstrated that the reversal effect of FFPM on cognitive deficits in APP/PS1 transgenic mice might be related to stimulation of the cAMP/PKA/CREB/BDNF pathway and anti-inflammatory effects. Moreover, FFPM appears to have potential as an effective PDE4 inhibitor in AD treatment with little emetic potential.

C-Reactive Protein Induces Tau Hyperphosphorylation via GSK3ß Signaling Pathway in SH-SY5Y Cells.

Amyloid plaques and neurofibrillary tangles are the key pathological features of Alzheimer's disease (AD). Studies have shown that C-reactive protein (CRP) increases during inflammatory reactions and, therefore, has been associated with AD. However, there is no published report relating the impact of CRP to the regulation of tau phosphorylation. In the present study, we investigated the effects of CRP on the phosphorylation of tau protein in SH-SY5Y cells. Treatment of cells with CRP (5, 10, 20 µg/ml) resulted in neurotoxicity and apoptosis, as was observed by MTT assay and Hoechst staining, respectively. Western blot analysis showed that CRP, in a time- and concentration-dependent manner, induced the phosphorylation of tau at Ser202 and ser396 in SH-SY5Y cells. Phosphorylation of Akt (Ser473) and GSK3ß (Ser9) were decreased by CRP treatment, whereas phosphorylation of ERK and p38 were not affected. Pharmacological inhibition of GSK3ß reversed the effects induced by CRP, viz., cytotoxicity, apoptosis, and tau phosphorylation. Herein, we present a novel mechanism of cell death following CRP insult, which activates tau hyperphosphorylation by regulating GSK3ß activity. CRP could potentially be used as an important pathological factor for the therapeutic intervention of AD.

[Remote correlations between situation indicators of rice leaf roller during its immigration period in Jiangsu Province and sea surface temperature of west Pacific as well as their long-term prediction models].

The correlations between the situation indicators (peak time of ingoing, last length of peak period, and moth quantity in peak period) of rice leaf roller in Yixing, Yandu and Jingjiang of Jiangsu Province and the grid monthly sea surface temperature (SST) of west Pacific were analyzed by statistical method, and the correlation maps were produced by using GRADS software. The regions in which the SST was significantly correlated with the situation indicators were identified, and the SST at these regions, which was processed by optimization correlation technique, was used as the predictor to set up the long-term models for predicting the situation indicators of rice leaf roller during its immigration period in the three regions. The results showed that the immigration time of rice leaf roller in each of the regions was highly correlated with the SST in that region, and the duration of immigration peak was well correlated with the SST of west Pacific. The correlations between moth amount and SST were significant and stable, and showed some seasonality. Model calibrations indicated that the agreements between outputs from all models and observations were statistically significant (alpha = 0.01), and model validations demonstrated the applicability of the models developed in this study in predicting the situation indicators of rice leaf roller. These models were capable of predicting the possible occurrence situation of rice leaf roller one to two months in advance, being of significance in the prevention and control of rice leaf roller, suitable management of rice production, reduction of pesticide pollution, and protection of environment.