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As a neurodegenerative disease, Alzheimer's disease (AD) seriously affects the health of older people. It is now known that changes in synapses occur first in the course of disease, perhaps even before the formation of Aβ plaques. Histone deacetylase (HDAC) can mediate the damage of Aβ oligomers to dendritic spines. Therefore, we examined the relationship between HDAC activity and synaptic defects by using an HDACI, BG45 in Human neuroblastoma SH-SY5Y cell line with stable overexpression of Swedish mutant APP (APPsw) and in APP/Ps1 transgenic mice during this study. The cells were treated with 15µM BG45 and the APP/Ps1 mice 30mg/kg BG45. We detected the level of synapse-related proteins, HDACs, tau phosphorylation and AMPA receptors by western bloting and immunohistochemistry. We also measured the expression of cytoskeletal proteins in the cell model. The mRNA level of GRIK2, SCN3B, SYNPR, Grm2, Grid2IP, GRIP1,GRIP2 were. to explore the effects of HDACi on regulating the synaptic proteins and AMPA receptors. Our studies demonstrated that the expression of HDAC1、HDAC2 and HDAC3 was increased, which was accompanied by the downregulation of the synapse-related proteins synaptophysin (SYP), postsynaptic dendritic protein (PSD-95) and spinophilin as early as 24 h after transfection with APPsw gene. BG45 upregulated the expression of synapse-related proteins and repaired cytoskeletal damage. In vivo, BG45 alleviated the apoptotic loss of hippocampal neurons, upregulated synapse-related proteins, reduced Aβ deposition and phosphorylation of tau and increased the level of the synapse-related genes GRIK2, SCN3B, SYNPR, Grm2, and Grid2IP. BG45 increased the expression of the AMPA receptor subunits GluA1, GluA2 and GluA3 on APPsw-transfected cells and increased GRIP1 and GRIP2 expression and AMPA receptor phosphorylation in vivo. These results suggest that HDACs are involved in the early process of synaptic defects of AD and that BG45 may rescue synaptic damage and loss of hippocampal neurons by specifically inhibiting HDAC1、HDAC2 and HDAC3, thereby modulating AMPA receptor transduction, increasing synapse-related gene expression and finally improving excitatory synapses. BG45 may be considered as a potential drug for the treatment of early AD for further study.

Methamphetamine (METH) leads to nervous system toxicity. Long-term exposure to METH results in damage to dopamine neurons in the ventral tegmental area (VTA), and depression-like behavior is a clinical symptom of this toxicity. The current study was designed to investigate whether the antioxidant tertiary butylhydroquinone (TBHQ) can alleviate neurotoxicity through both antioxidative stress and antiapoptotic signaling pathways in the VTA. Rats were randomly divided into a control group, a METH-treated group (METH group), and a METH+TBHQ-treated group (METH+TBHQ group). Intraperitoneal injections of METH at a dose of 10 mg/kg were administered to the rats in the METH and METH+TBHQ groups for one week, and METH was then administered at a dose that increased by 1 mg/kg per week until the sixth week, when the daily dosage reached 15 mg/kg. The rats in the METH+TBHQ group received 12.5 mg/kg TBHQ intragastrically. Chronic exposure to METH resulted in increased immobility times in the forced swimming test (FST) and tail suspension test (TST) and led to depression-like behavior. The production of reactive oxygen species (ROS) and apoptosis levels were increased in the VTA of animals in the METH-treated group. METH downregulated Nrf2, HO-1, PI3K, and AKT, key factors of oxidative stress, and the apoptosis signaling pathway. Moreover, METH increased the caspase-3 immunocontent. These changes were reversed by treatment with the antioxidant TBHQ. The results indicate that TBHQ can enhance Nrf2-induced antioxidative stress and PI3K-induced antiapoptotic effects, which can alleviate METH-induced ROS and apoptosis, and that the crosstalk between Nrf2 and PI3K/AKT is likely the key factor involved in the protective effect of TBHQ against METH-induced chronic nervous system toxicity.

Brain-derived neurotrophic factor (BDNF) plays an important role in promoting the growth, differentiation, survival and synaptic stability of neurons. Presently, the transplantation of neural stem cells (NSCs) is known to induce neural repair to some extent after injury or disease. In this study, to investigate whether NSCs genetically modified to encode the BDNF gene (BDNF/NSCs) would further enhance synaptogenesis, BDNF/NSCs or naive NSCs were directly engrafted into lesions in a rat model of traumatic brain injury (TBI). Immunohistochemistry, western blotting and RT-PCR were performed to detect synaptic proteins, BDNF-TrkB and its downstream signaling pathways, at 1, 2, 3 or 4 weeks after transplantation. Our results showed that BDNF significantly increased the expression levels of the TrkB receptor gene and the phosphorylation of the TrkB protein in the lesions. The expression levels of Ras, phosphorylated Erk1/2 and postsynaptic density protein-95 were elevated in the BDNF/NSCs-transplanted groups compared with those in the NSCs-transplanted groups throughout the experimental period. Moreover, the nuclear factor (erythroid-derived 2)-like 2/Thioredoxin (Nrf2/Trx) axis, which is a specific therapeutic target for the treatment of injury or cell death, was upregulated by BDNF overexpression. Therefore, we determined that the increased synaptic proteins level implicated in synaptogenesis might be associated with the activation of the MAPK/Erk1/2 signaling pathway and the upregulation of the antioxidant agent Trx modified by BDNF-TrkB following the BDNF/NSCs transplantation after TBI.

Diabetic encephalopathy (DE) has been defined as one of the major complications of diabetes, characterized by neurochemical and neurodegenerative changes. However, the molecular mechanism of DE are not fully elucidated at present. Here, the primary hippocampal neurons were cultured in vitro with high glucose (HG) to induce diabetes-like effects, and mice were given streptozotocin (STZ) to induce a model of type 1 diabetes mellitus (T1D) mice. The administration of sulforaphane (SF) were used to observe the protective effects on the hippocampal neurons. We found that the expression of glucose-regulated protein 78 (GRP78), a typical endoplasmic reticulum chaperone, showed a trend of increasing in the early phase but decreasing in the late phase of both HG-induced primary hippocampal neurons and T1D mice. However, SF suppressed the apoptosis induced by HG in vitro and in vivo through TUNEL assay and caspase-3 immunohistochemistry staining. Meanwhile, the administration of SF suppressed the upregulation of CHOP, Bax and p-JNK protein and the downregulation of Bcl-2 protein induced by HG in hippocampal neurons in vitro and in vivo. The caspase-12 gene was upregulated only at 4 weeks in T1D mice compared with control mice, and the upregulation was suppressed by SF. In addition, the combined administration of SF and PX12, which is an inhibitor of thioredoxin (Trx), eliminated the protective effects of SF. We conclude that HG induced the development of endoplasmic reticulum stress (ERS) in hippocampal neurons, eventually leading to the apoptosis of neurons. SF prevented the ERS and attenuates the hippocampal neuron apoptosis induced by HG both in vitro and in vivo. The underlying mechanism may be involved in the suppression of the CHOP-Bax/Bcl-2, JNK and caspase-12 signaling pathways by SF through the Trx-1 target protein.

We assessed the neuroprotective effects of Lycium barbarum Polysaccharides (LBP) on photoreceptor degeneration and the mechanisms involved in oxidative stress in light-exposed mouse retinas. Mice were given a gavage of LBP (150 mg/kg or 300 mg/kg) or phosphate buffered saline (PBS) for 7 days before exposure to light (5000 lx for 24 h). We found that LBP significantly improved the electroretinography (ERG) amplitudes of the a- and b-waves that had been attenuated by light exposure. In addition, changes caused by light exposure including photoreceptor cell loss, nuclear condensation, an increased number of mitochondria vacuoles, outer membrane disc swelling and cristae fractures were distinctly ameliorated by LBP. LBP treatment also significantly prevented the generation of reactive oxygen species (ROS) compared with PBS treatment. The levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and thioredoxin reductase (TrxR1) mRNA were decreased in PBS-treated mice compared with controls but increased remarkably in LBP-treated mice. The mRNA levels of the DNA repair gene Poly (ADP-ribose) polymerase (PARP14) was increased in PBS-treated mice but decreased significantly in the LBP-treated mice. Our findings indicate that pretreatment with LBP effectively protected photoreceptor cells against light-induced retinal damage probably through the up-regulation of the antioxidative genes Nrf2 and TrxR1, the elimination of oxygen free radicals, and the subsequent reduction in the mitochondrial reaction to oxidative stress and enhancement in antioxidant capacity. In addition, the decreased level of PARP14 mRNA in LBP-treated mice also indicated a protective effect of LBP on delaying photoreceptor in the light-damaged retina.

Strengthening the combination of science and technology finance is an important means to implement innovation driven development strategy.Since 2011, the Ministry of science and technology in conjunction with the eight ministries, the Ministry of finance, people's Bank of China and other selected 16 Beijing Zhongguancun, Chengdu hi tech Zone, Shanghai, Wuhan and other areas, to actively promote the combination of technology and finance pilot work, explore the new mechanism of scientific and technological resources and financial resources docking, and made significant progress.This paper attempts to sum up the experience of the pilot areas of scientific and technological financial innovation, in order to provide a good reference for the further development of Inner Mongolia's science and technology finance. Science and technology finance is an important part of the national science and technology innovation system and the financial system. It is the close combination of the "first productivity" and "the first impetus".In order to realize the strategy of "independent innovation country", in recent years, our country vigorously promote the development of science and technology finance.In October 2011, the Ministry of science and technology, the Ministry of Finance and other eight ministries jointly developed a number of Guiding Opinions on promoting the combination of technology and finance to accelerate the implementation of independent innovation strategy;At the same time, the Ministry of science and technology in conjunction with the "three" joint determination of sixteen regions of Beijing, Zhongguancun Chengdu high tech Zone to carry out pilot technology and financial integration, financial innovation of science and technology ushered in a new opportunity.The pilot areas in the promotion of science and technology in the financial sector, overall planning, system construction, financial services model and product innovation has many new breakthroughs, in the nationwide promotion of technology and Finance Based on the accumulated the rich experience in the demonstration.To conform to the national policy, combined with the autonomous region in the long-term science and technology development plan, Inner Mongolia has actively carried out the combination of technology and finance,After several years of efforts, in the construction of technology financial services system has achieved certain results First, the domestic pilot areas of scientific and technological financial development experience summary. (a) Pay attention to the innovation of science and technology financial policy The development of science and technology financial innovation depends on the regulation and guidance of government policy.In recent years, the pilot areas in under the guidance of the policy document of the national programme, attaches great importance to local policies and regulations of construction and innovation, mainly involved in the field include fiscal guidance (entrepreneurial venture investment fund, angel investment guide fund), risk compensation mechanism construction technology interest payments on loans and credit risk compensation, science and technology insurance subsidies, small and medium enterprises credit guarantee fund, financial institutions, the innovation of the forms of (technology banking or Commercial Bank branch of science and technology, science and technology of small loan companies, financing guarantee institutions), service system (Science and technology management, combination of technology and Finance, financial service platform of science and technology, Regional OTC market) etc.. 5th International Conference on Social Science, Education and Humanities Research (SSEHR 2016) © 2016. The authors Published by Atlantis Press 1291 (b) Pay attention to the innovation of science and technology finance development model As the basis of scientific and technological innovation, the degree of development of financial markets, the layout of the emerging industries and geographical and cultural differences in the environment,Financial development in science and technology could not apply a fixed model, in view of the reality of the situation, many pilot areas have innovation explore apply to local financial and technological development, and achieved good results, provides referential sample for other parts of the country.The following are some of the more typical models:(1) Zhongguancun Beijing model.The research gold cooperation mechanism innovation is the biggest feature, research cooperation mechanism refers to the new industry and universities and research institutions + enterprise R & D + financial institutions,the purpose is through resource integration,to set up all kinds of cooperation alliance, play alliance members each in terms of resource, technology, brand, capital and other advantages innovative mechanisms for cooperation, expand areas of cooperation and ultimately promote the Zhongguancun Science and Technology Park financial services innovation system construction.(2) the development model of Shanghai Zhangjiang hi tech park, a base, a center, a product, five pilot " (c) Pay attention to the innovation of the financial system of science and technology Science and technology financial system mainly includes two aspects: the financial system and the market science and technology financial system.The financial system is mainly embodied in the way of financial investment in science and technology innovation, science and technology, science and technology insurance credit compensation and reward subsidies and policy financing guarantee system innovation etc..Market of science and technology innovation in the financial system cover all non public finance of science and technology in the financial sector, including multiple areas of the development of bank credit system innovation, new technology of financial institutions and the multi-level capital market system innovation.System is an important guarantee for the smooth development of science and technology finance, all over the country attaches great importance to the innovation and construction of the financial system of science and technology, innovation and innovation. (d) Focus on the construction of science and technology financial services center Throughout the financial services technology center of the organizational structure, functions, business content, operation mechanism from the point of view, the financial service center of science can be summarized for financing, guarantees, insurance, assessment, consulting, legal, finance, training and other functions as one of the integrated service platform.It guides as government funds , the effective integration of all kinds of scientific and technological projects and enterprises, such as all kinds of elements of science and technology and financial capital, financial capital, and other capital elements, innovative financial products and tools, effectively alleviate the investment and financing information asymmetry of contradiction, financing needs of the different stages of the development of small and medium sized enterprises of science and technology, providing a one-stop, personalized financial services, achieve science and technology, the financial resources to gather together sharing and efficient docking. Two, Inner Mongolia science and technology financial development present situation and problem analysis. (a) Inner Mongolia science and technology finance development present situation 1. the preliminary establishment of the working mechanism of the combination of science and technology and Finance With the state of science and technology and the continuous progress of the financial work, the Inner Mongolia science and technology financial work has been launched, the introduction of a number of special policies, and establish a government related departments of the work mechanism.In December 2011, the autonomous region science and technology department in conjunction with the Department of finance, "a line of three Bureau jointly issued" to promote the Inner Mongolia Autonomous Region Science and technology financial work combined with the certain opinions ", put forward the combination of technology and financial goals, main task and specific safeguard measures.Subsequently, the Inner Mongolia Autonomous Region Science and

Caveolin-1 is the major component protein of caveolae and associated with a lot of cellular events such as endocytosis, cholesterol homeostasis, signal transduction, and tumorigenesis. The majority of results suggest that caveolin-1 might not only act as a tumor suppressor gene but also a promoting metastasis gene. In this study, the divergent expression and roles of caveolin-1 were investigated in mouse hepatocarcinoma cell lines Hca-F, Hca-P, and Hepa1-6, which have high, low, and no metastatic potential in the lymph nodes, as compared with normal mouse liver cell line IAR-20. The results showed that expression of caveolin-1 mRNA and protein along with the amount of caveolae number in Hca-F cells was higher than that in Hca-P cells, but was not detectable in Hepa1-6 cells. When caveolin-1 expression in Hca-F cells was down-regulated by RNAi approach, Hca-F cells proliferation rate in vitro declined and the expression of lymphangiogenic factor VEGFA in Hca-F decreased as well. Furthermore, in vivo implantation assay indicated that reduction of caveolin-1 expression in Hca-F prevented the lymphatic metastasis tumor burden of Hca-F cells in 615 mice. These results suggest that caveolin-1 facilities the lymphatic metastasis ability of mouse hepatocarcinoma cells via regulation tumor cell growth and VEGFA expression.

Cytoskeletal proteins are involved in neuronal survival. Brain-derived neurotrophic factor can increase expression of cytoskeletal proteins during regeneration after axonal injury. However, the effect of neural stem cells genetically modified by brain-derived neurotrophic factor transplantation on neuronal survival in the injury site still remains unclear. To examine this, we established a rat model of traumatic brain injury by controlled cortical impact. At 72 hours after injury, 2 × 107 cells/mL neural stem cells overexpressing brain-derived neurotrophic factor or naive neural stem cells (3 mL) were injected into the injured cortex. At 1–3 weeks after transplantation, expression of neurofilament 200, microtubule-associated protein 2, actin, calmodulin, and beta-catenin were remarkably increased in the injury sites. These findings confirm that brain-derived neurotrophic factor-transfected neural stem cells contribute to neuronal survival, growth, and differentiation in the injury sites. The underlying mechanisms may be associated with increased expression of cytoskeletal proteins and the Wnt/β-catenin signaling pathway.

Long-term abuse of alcohol results in chronic alcoholic myopathy which is associated with increased oxidative stress. Ginkgo biloba extract (EGB) is widely used as a therapeutic agent to treat certain cardiovascular and neurological disorders. Although EGB is known to possess antioxidant functions and potent cytoprotective effects, its protective mechanism on alcohol-induced oxidative damage in C2C12 myoblasts remains unclear. In this study, we investigated the cytoprotective mechanisms of EGB against alcohol-derived oxidative stress in mouse C2C12 myoblasts. Challenge with alcohol (100mM) caused an increase in intracellular reactive oxygen species in mouse C2C12 myoblasts, which was not alleviated by treatment with EGB. These results indicate that EGB does not seem to act as an ROS scavenger in this experimental model. Additionally, EGB produced activation of ERK and JNK [two major mitogen-activated protein kinases (MAPKs)], an increase in the nuclear level of nuclear factor erythroid-2-related factor 2 (Nrf2) and upregulation of heme oxygenase-1 (HO-1, a stress-responsive protein with antioxidant function). Pretreatment with inhibitors of MAPKs PD98059 (a specific inhibitor of ERK), SP600125 (a specific inhibitor of JNK) abolished both EGB-induced Nrf2 nuclear translocation and HO-1 up-regulation. We conclude that EGB confers cytoprotective effects from oxidative stress induced by alcohol in mouse C2C12 myoblasts depend on transcriptional upregulation of HO-1 by EGB via the MAPKs/Nrf2 pathway.

This study evaluated the effects of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) on injured gastrocnemius, soleus and plantaris muscles, induced by alcohol in rats. A total of 60 male Sprague-Dawley rats (2.5 months old, 200 ± 20 g) were divided into 6 groups: i) untreated skeletal muscle and analyzed 2 weeks later (A1 group, 5 rats); ii) untreated skeletal muscle and analyzed 6 weeks later (A2 group, 5 rats); iii) untreated skeletal muscle and analyzed 12 weeks later (A3 group, 5 rats); iv) injured skeletal muscle and analyzed 2 weeks later (B1 group, 15 rats); v) injured skeletal muscle and analyzed 6 weeks later (B2 group, 15 rats); and vi) injured skeletal muscle and analyzed 12 weeks later (B3 group, 15 rats). The injured and uninjured muscles were observed by light microscopy and polarization microscopy. The MMP activity was evaluated through zymography, and messenger RNA (mRNA) of MMP-9 and of MMP-2 were assessed by RT-PCR. The expression of MMP-9 was assessed by Western blot analysis. The plantaris and gastrocnemius muscles in the rats subjected to alcohol ingestion were found to have a high expression of MMP-9, but not of MMP-2. Picrosirius red staining was used to assess whether increased fibrosis in the skeletal muscle was associated with alcohol exposure in rats. The study indicated that alcohol may be involved in the skeletal muscle interstitial fibrosis in our model of alcohol-exposed rats through increased MMP-9 expression, and that this increased expression may aggravate the development of prolonged alcohol muscle injury.

RIMs (Rab3-interacting molecules) are synaptic proteins essential for neural transmission and plasticity. RIM1alpha has been implicated in membrane trafficking and regulation of secretory vesicle exocytosis in eukaryotic cells. Little information is as yet available on RIM3gamma. In the present study, we investigated the cellular expression, subcellular distribution, and possible functions of RIM3gamma in the rat CNS. Rim3gamma cDNA was subcloned and the protein expressed in vitro for the generation and purification of a rabbit anti-RIM3gamma polyclonal antibody. In situ hybridization histochemistry, immunohistochemistry, and immunoelectron microscopy were performed to map expression of the mRNA and protein in the rat CNS. Our results indicated widespread distribution of RIM3gamma in diverse CNS neuronal cell types. The mRNA was found mainly in the cell bodies, whereas the protein immunoreactivity was localized chiefly to neuronal dendrites and to the postsynaptic densities as visualized under the light and electron microscope. This postsynaptic placement of RIM3gamma is distinct from the presynaptic localization of RIM1alpha but may contribute to regulating synaptic transmission and plasticity. The identification of RIM3gamma as a postsynaptic protein has functional implications for CNS synapse functions.

Previous studies showed that nitricoxide synthase (NOS) and oxidative stress can induce skeletal muscle atrophy in the muscular dystrophy and inclusion-body myopathy. There is a correlation between NOS and oxidative stress. However, it is not clear, whether there are some changes of the NOS activity in prolonged alcoholic myopathy (PAM), and whether NOS activity has relation to amyotrophy of PAM. We established experimental alcoholic myopathy model of rats by prolonged alcohol intake. We found that there is a reduction in GSH-px (P0.05) and an increase of SOD (P0.05), MDA (P0.05) and iNOS (P0.05) in the plantaris of the experimental group by spectrophotometer. In the soleus of the experimental group, except for MDA showed an increase (P0.05), the other enzymes showed no obvious difference (P0.05). The immunohistochemistry results showed that there was obvious expression of iNOS in the cytoplasm of plantaris in the experimental group and there was no expression of iNOS in the control group. There was a decrease of nNOS expression on the membranes of the plantaris cells in the experimental group by immunofluorescence. Meanwhile, we found the expression of nNOS in some cytoplasm. Our results suggested that NOS might be an important factor during the development of PAM. We could infer that there are some disturbances with regard to output and scavenging of free radical in PAM. Alcohol can induce the oxidative stress reaction and further result in imbalance of the oxidant-antioxidant status in the organism.

CXC chemokine recepter-4 (CXCR4) and its ligand, stromal cell-derived factor-1alpha (SDF-1alpha) have been implicated in the organ-specific metastasis of several malignancies. Hca-F and its syngeneic cell line Hca-P are mouse hepatocarcinoma cell lines with high and low potential of lymphatic metastasis, respectively. Previous studies showed that the secretion of matrix metalloproteinases (MMPs) associated with the metastatic ability of Hca-F and Hca-P cell line depending on the lymph node environment. However, the mechanism of this process has remained unclear. This study investigated the roles of CXCR4 on Hca-F cell and SDF-1alpha of lymph node in lymphatic metastasis. The RT-PCR and Flow cytometry analysis results show that Hca-F cells express higher level CXCR4 mRNA and cell-surface CXCR4 protein, as compared with Hca-P cells. Treatment of recombinant SDF-1alpha proteins induced greater amount of calcium-flux in Hca-F cells than that in Hca-P cells, demonstrating higher functional CXCR4 expression on Hca-F cells than that on Hca-P cells. Furthermore, both the cell-free extratcs of lymph node and recombinant SDF-1alpha proteins induced secretions of active MMP-9 and MMP-2 from Hca-F cells in vitro. But those secretions were significantly reduced by blockade of cell surface CXCR4 with rabbit anti-mouse CXCR4 polyclonal antibody (pAb) and neutralization of SDF-1alpha in lymph node extracts with rabbit anti-mouse SDF-1alpha pAb as well. These results suggest that the CXCR4/SDF-1alpha system mediates active MMP-9 and MMP-2 secretion from Hca-F and Hca-P cells, which facilitates lymphogenous metastasis of those cells consequently.

In the process of screening cell-type-specific genes, we identified juxtanodin (JN), an oligodendroglial protein featuring a putative C-terminal actin-binding domain. At the cellular level, JN in the rat CNS colocalized with 2′,3′-cyclic nucleotide-3′-phosphodiesterase (CNPase), a cytoskeleton-related oligodendroglial protein. In the myelin sheath, JN was found mainly in the abaxon and the lateral few terminal loops. Its apposition to the myelinated axon, through the latter, defined an axonal subregion, herewith termed juxtanode, at the Ranvier node-paranode junction. During forebrain ontogenesis, JN expression paralleled that of MBPs but lagged behind CNPase. Juxtanodin transfection promoted arborization of cultured OLN-93 cells and augmented endogenous CNPase expression and transport to the process arbors of cultured primary oligodendrocyte precursors. These results reveal JN as a cytoskeleton-related oligodendroglial protein that delineates the juxtanode and might serve oligodendrocyte motility, differentiation, or myelin-axon signaling. Functionally, JN may be involved in CNS myelination and/or specialization of the node of Ranvier.