Gold Nanorods with Spatial Separation of CeO2 Deposition for Plasmonic-Enhanced Antioxidant Stress and Photothermal Therapy of Alzheimer's Disease.

Activities of catalase (CAT) and superoxide dismutase (SOD) of ceria nanoparticles (CeO2 NPs) provide the possibility for their application in nervous system oxidative stress diseases including Alzheimer's disease (AD). The addition of hot electrons produced by a plasma photothermal effect can expand the photocatalytic activity of CeO2 to the near-infrared region (NIR), significantly improving its redox performance. Therefore, we coated both ends of gold nanorods (Au NRs) with CeO2 NPs, and photocatalysis and photothermal therapy in the NIR are introduced into the treatment of AD. Meanwhile, the spatially separate structure enhances the catalytic performance and photothermal conversion efficiency. In addition, the photothermal effect significantly improves the permeability of the blood-brain barrier (BBB) and overcomes the shortcomings of traditional anti-AD drugs. To further improve the therapeutic efficiency, Aß-targeted inhibitory peptides were modified on the middle surface of gold nanorods to synthesize KLVFF@Au-CeO2 (K-CAC) nanocomposites. We have verified their biocompatibility and therapeutic effectiveness at multiple levels in vitro and in vivo, which have a profound impact on the research and clinical transformation of nanotechnology in AD therapy.

Carbon nitride-based nanocaptor: An intelligent nanosystem with metal ions chelating effect for enhanced magnetic targeting phototherapy of Alzheimer's disease.

Metal ions imbalance, a well-established pathologic feature of alzheimer's disease (AD), ultimately results in the deposition of amyloid-ß peptide (Aß) proteins and Aß-induced neurotoxicity. Herein, to overcome these hurdles, an intelligent Aß nanocaptor with the capacity to chelate metal ions and targeted therapy is developed by anchoring carbon nitride (C3N4) nanodots to Fe3O4@mesoporous silica nanospheres, and decorated with benzothiazole aniline (BTA) (designated as B-FeCN). The C3N4 nanodots could effectively capture superfluous Cu2+ to suppress the formation of Cu2+-Aß complex thereby eliminating Aß aggregation. Simultaneously, the nanocaptor enables local low-temperature hyperthermia to promote the dissolution of preformed fiber precipitates, therefore, maximizing the therapeutic benefits. Owing to its favorable photothermal effect, the blood-brain barrier (BBB) permeability of the nanocaptor is noticeably ameliorated upon laser illumination, which conquers the limitations associated with traditional anti-AD drugs, as evidenced by in vivo and in vitro studies. Besides, leveraging on the magnetic properties of Fe3O4 core, the nanocaptor is magnetized to access to the targeted Aß regions under extrinsic magnetic field. BTA conjugation, which specifically binds to the ß2 position of the Aß fibers, executes specific targeting at Aß plaques, and synchronously endows the BTA-modified nanocaptor with fluorescent imaging property for sensitively detecting Aß aggregates. In view of these superiorities, nanocaptors combine metallostasis restoration and Aß targeted therapy can surmount the interference of copper ions, enhance BBB permeability and protect cells against Aß-induced neurotoxicity, which provides new avenues for developing neuroprotective nanosystems for the treatment of alzheimer's disease.

Osthole alleviates MPTP-induced Parkinson's disease mice by suppressing Notch signaling pathway.

Objectives: Parkinson's disease (PD) is an age-related neurodegenerative disease characterized by motor dysfunctions. Dopaminergic neuron loss, inflammation and oxidative stress responses play key roles in the pathogenisis of PD. Osthole (Ost), a natural coumarin derivative, isolated from various herbs such as Cnidium monnieri (L.), has anti-inflammatory, anti-apoptotic and anti-oxidative stress properties. However, whether it has effects on PD is unknown. Methods: In this study, mice were subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injection to induce PD symptoms, and treated with osthole. Stepping and cylinder tests were performed to determine their motor function. Immunohistochemical and immunofluorescence staining were performed to detect tyrosine hydroxylase (TH) and ionized calcium binding adaptor molecule 1 (Iba-1). The expression levels of inflammatory cytokines and oxidative stress factors were detected by qPCR and ELISA. Notch signaling pathway was investigated by western blot. Results: We found that injection of MPTP induced motor deficits in mice, enhanced the loss dopaminergic neurons and the activation of microglia, increased inflammatory and oxidative stress responses, and inhibited Notch signaling pathway. Osthole treatment suppressed theses MPTP-induced alterations. Conclusion: In conclusion, osthole attenuates PD symptoms by suppressing Notch signaling pathway.

Cerebrospinal fluid-stem cell interactions may pave the path for cell-based therapy in neurological diseases.

Recent studies have suggested that the regulation of endogenous neural stem cells (NSCs) or transplanting of exogenous nerve cells are the newest and most promising methods for the treatment of dementia and other neurological diseases. The special location and limited number of endogenous NSCs, however, restrict their clinical application. The success in directional differentiation of exogenous stem cells from other tissue sources into neural cells has provided a novel source for NSCs. Study on the relative mechanisms is still at the preliminary stage. Currently the induction methods include: 1) cell growth factor induction; 2) chemical induction; 3) combined growth factor-chemical induction; or 4) other induction methods such as traumatic brain tissue homogenate, gene transfection, traditional Chinese medicine, and coculture induction. Cerebrospinal fluid (CSF), as a natural medium under physiological conditions, contains a variety of progrowth peptide factors that can promote the proliferation and differentiation of mesenchymal stromal cells (MSCs) into neural cells through the corresponding receptors on the cell surface. This suggests that CSF can not only nourish the nerve cells, but also become an effective and suitable inducer to increase the yield of NSCs. However, some other studies believed that CSF contained certain inhibitory components against the differentiation of primary stem cells into mature neural cells. Based on the above background, here we review the relative literature on the influence of the CSF on stem cells in order to provide a more comprehensive reference for the wide clinical application of NSCs in the future.

Serum 25-hydroxyvitamin D deficiency predicts long-term poor prognosis among ischemic stroke patients without hyperglycaemia.

BACKGROUND: It is unclear whether 25-hydroxyvitamin D [25(OH)D] has a protective effect on long-term prognosis of ischemic stroke and whether it is affected by blood glucose levels. We aim to examine the effect of serum vitamin D especially its deficiency on 1-year poor outcome of ischemic stroke patients in total patients and by blood glucose subgroups. METHODS: A total of 3041 ischemic patients from China Antihypertensive Trial in Acute Ischemic Stroke were included. The serum concentrations of 25(OH)D were measured at baseline. All subjects were followed up for death and vascular events at 1year after acute ischemic stroke. RESULTS: Among total ischemic stroke patients and those with hyperglycemia, 25(OH)D deficiency was not associated with the risk of vascular events and death. In the normoglycemic subgroup, 25(OH)D deficiency subjects had a significantly higher risk of poor prognosis compared with those with 25(OH)D≥20ng/ml. The hazard ratio (95% confidence interval) was 1.58(1.04-2.41) in the multivariable adjusted model (P for linear trend=0.02). CONCLUSION: Serum 25(OH)D deficiency may be merely an independent risk factor of 1-year poor prognosis in ischemic stroke patients without hyperglycemia. Future studies about improving long-term prognosis of ischemic stroke by vitamin D supplementation could be first applied to these patients.

EGb-761 Attenuates the Anti-proliferative Activity of Fluoride via DDK1 in PC-12 Cells.

EGb-761 is commonly used as a treatment for ischemic brain injury, neurodegenerative diseases and some types of tumors (Christen and Maixent, in Cell Mol Biol 48(6):601-611, 2002). However, it is unclear whether EGb-761 affects the proliferation of cells exposed to fluoride. In this study, the proliferation and apoptosis of PC-12 cells exposed to fluoride were investigated and EGb-761 was used to protect PC-12 cells against the effects of fluoride. We found that the canonical Wnt signaling pathway was involved in the anti-proliferation of PC-12 cells exposed to fluoride. Furthermore, the results also showed that EGb-761 could attenuate the anti-proliferative activity of fluoride via DDK1 in PC-12 cells. This study may provide a new method for protecting against the inhibition of cell proliferation induced by fluoride.

The analog of Ginkgo biloba extract 761 is a protective factor of cognitive impairment induced by chronic fluorosis.

Ginkgo biloba extract EGb761 is widely used to treat patients with learning and memory impairment in Alzheimer's disease and Parkinson's disease in China. However, it is not yet clear whether the analog of EGb761 (EGb) has a protective effect on the learning and memory damage induced by chronic fluorosis. In this study, 30 Wistar rats were randomly divided into three groups: a control group, a sodium fluoride (NaF) + EGb group, and a NaF group. The rats were administered 0.5 ml water containing NaF (100 mg/l) and EGb (120 mg/kg) per day via gavage. After 3 months, the rats' capacity for learning and memory was tested using a Y-maze. Damage to hippocampal neurons was evaluated by histological examination of the CA3 area. Superoxide dismutase (SOD) activity and the levels of glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured. Furthermore, the expression levels of Bcl-2 and Bax and the levels of cleaved Caspase3 in the hippocampus were evaluated by RT-PCR and Western blotting. The results showed that EGb could improve learning and memory abilities, enhance the activities of SOD and GSH-Px, attenuate the level of MDA, upregulate the ratio of Bcl-2/Bax, and downregulate the level of cleaved Caspase3.

[Effects of electroacupuncture plus oxygenmedicine on the expression of Bcl-2 and Bax proteins in the hippocampal CA 1 area in rats with global cerebral ischemia/reperfusion injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) plus oxygenmedicine (OM) on the expression of Bcl-2 and Bax in the hippocampal CA 1 area in cerebral ischemia/reperfusion injury (CI/RI) rats. METHODS: Thirty SD rats were randomized into sham-operation, model, EA, OM, EA+OM groups (n=6 /group). CI/RI model was established by using modified Pulsinelli 4 vessel occlusion and reperfusion. EA (100 Hz, 3.5 mA) was applied to "Baihui" (GV 20) and "Zusanli" (ST 36) 30 min, once daily for 4 days. Rats of OM and EA+ OM groups were put into a box filled with oxygen and atomized herbal medicines containing Bingpian (Borneolum), Shexiang (Moschus), Huangjing (Rhizoma Polygonati), Shouwu (Radix Polygoni Multiflori), etc. for 30 min, once daily for 4 days. Bcl-2 and Bax expression of the hippocampal CA 1 area was detected by immunohistochemistry. RESULTS: Compared with sham group, the numbers of Bcl-2 immunoreaction (IR) and Bax IR positive cells, and the immunoactivity of Bcl-2 IR and Bax IR positive products in the hippocampal CA 1 area were increased significantly in model group (P < 0.05, P < 0.01). In comparison with model group, the number of Bcl-2 IR positive cells and Bcl-2 immunoactivity in EA, OM and EA+OM groups increased considerably (P < 0.01), while Bax IR positive cell numbers and Bax immunoactivity in EA, OM and OM+ EA groups decreased significantly (P < 0.01). The effects of EA+ OM were significantly superior to those of EA and OM groups in upregulating Bcl-2 IR positive cell number and Bcl-2 immunoactivity and downregulating Bax IR positive cell number and Bax immunoactivity (P < 0.01). No significant differences were found between EA and OM groups in the abovemen-EA and OM and EA+OM can effectively regulate the expression of Bcl-2 and Bax in tioned indexes (P > 0.05). CONCLUSION: EA and OM and EA + OM can effectively regulate the expression of Bcl-2 and Bax in the hippocampal CA 1 area in CI/RI rats, and the effects of EA+OM are significantly superior to those of simple EA and simple OM, which may contribute to their effect in improving cerebral ischemia.