Endoplasmic reticulum(ER)stress can be caused by disturbances in the function of the ER with the accumulation of misfolded proteins.The ER response is characterized by unfolded protein response(UPR)causing translational attenuation,induction of ER chaperones and degradation of misfolded proteins.In case of prolonged or aggravated ER stress,cellular signals leading to apoptosis are activated.ER stress has been suggested to be involved in human neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease,and amyotrophic lateral sclerosis,as well as other disorders.Here we will discuss the neurotoxic effect of ER stress in these three major neurodegenerative diseases,and highlight current knowledge in this field that may reveal novel insight into disease mechanisms and help to design better therapies for these disorders.

MMP-9 is one of the family of matrix metalloproteinases, which degrades extracellular matrix. MMP-9 is induced by many inflammatory factors, including IL-1?,IL-8 and TNF-?. Meanwhile, MMP-9 potentiates inflammatory factors by aminoterminal processing. The signal transduction by which inflammatory factors induce MMP-9 is also an important part in recent research. This review will give a summary in all these fields.

Objective: The experiment was undertaken to explore the blood-brain barrier permeability and the gene expression of matrix metalloproteinase-9 (MMP-9) in ischemic cerebra and the impact of Buyanghuanwu Decoction on them. Methods: The (middle cerebral artery occlusion, MCAO) rat model was used. At 1h, 3h, 24h, 48h, 5d after reperfusion. They were measured. Results: In treatment group, the BBB permeability and the MMP-9 gene expression decreased. Conclusion: Buyanghuanwu Decoction can protect the BBB by inhibiting the MMP-9 gene expression.

0 05). The forelimb functional tests demonstrated that, the number of food pellets eaten by PD rats with the contralateral side of 6 OHDA lesion (17 71?4 82) was significantly reduced compared with the controls (34 43?3 55)( P

AIM: To investigate the changes of neuronal glutamate transporter (EAAC1) at different ischemic times in the rat hippocampus in early stage. METHODS: Brain microinjection of EAAC1 antisense oligodeoxyneucleotide (EAAC1 antisense) was adopted and focal transient ischemia was produced by the filament method of middle cerebral artery occlusion (MCAO). Western blotting and TTC staining analysis were adopted for observing EAAC1 expression and infarction volume in ischemic region .The expression of EAAC1 mRNA and protein at different ischemic times in the rat ischemic hippocampus was assessed by RT-PCR and Western blotting analysis. RESULTS: Compared with EAAC1 sense group, the volume of brain ischemic infarction [(105.67?8.70) mm~3] was reduced after brain microinjection of EAAC1 antisense. Compared with the sham-operated control, EAAC1 mRNA was significantly higher at 6 h and at (24 h) in the hippocampal regions during ischemia, while protein expression was higher at 24 h only. EAAC1 mRNA and protein expression were unchanged at other ischemic times. CONCLUSION: EAAC1 is associated with ischemic injury and its expression is increased in the hippocampal regions after focal cerebral ischemia.

Background and purpose:In recent years, many studies have showed that elemene liposome is widely used in the treatment of digestive tract tumors, malignant pleural effusion and ascites. This study combined in vitro and in vivoexperiments to observe the inhibitory effect of elemene liposome on the growth of human gastric cancer and the HGC-27 cell line.Methods:In order to screen the optimum concentration of elemene liposome, machine vision automatic live cell observation analysis system (Cell-IQ) was applied to detect the best inhibitory effect on human gastric cancer cell line HGC-27, and the lfow cytometry was applied to further detect the apoptosis of HGC-27 treated with elemene liposome. The model of human gastric cancer peritoneal metastasis in nude mice was established to investigate the intervention of elemene liposome and cisplatin (DDP) on peritoneal cancer index (PCI). CD31 marker of tumor microvessel density (MVD) and the expression of vascular endothelial growth factor (VEGF) in tumor tissues were investigated to explore the mechanism underlying the inhibitory effect on peritoneal metastasis of HGC-27 cells in nude mice.Results:Cell-IQ analysis showed that the inhibitory effect of elemene liposome on HGC-27 presented in a positive concentration-dependent manner, which could not be further enhanced when the concentration exceeded 100 μg/mL with the best reaction time between 4 and 19 hours. Flow cytometry showed that the early apoptosis rate was 45% in the elemene liposome group and only 0.019% in the control group. The early apoptosis rate was signiifcantly higher in treatment group than that in control group (P<0.05). PCI was signiifcantly lower in the group treated with elemene liposome plus DDP than that in control group (P<0.05) in the peritoneal metastasis of gastric cancer nude mice model. The expression of CD31-MVD and VEGF was not signiifcantly different between the treated and control groups (P>0.05).Conclusion:Elemene liposome can inhibit human gastric cancer cells at the optimal concentration of 100 μg/mL with the best reaction time between 4-19 hours. Elemene liposome has a clear preventive effect on peritoneal metastasis of human gastric cancer in nude mice. Induction of apoptosis in gastric cancer cells may be the main mechanism underlying the inhibitory effect of elemene liposome on human gastric cancer cells.

AIM:To investigate the integrative treatment of both coenzyme Q 10 ( CoQ10 ) and minocycline in the rats intranigrally intoxicated with 1-methyl-4-phenylpyridinium ( MPP+) .METHODS:The rat model of Parkinson disease ( PD) was established by intranigral microinjection of MPP +.The degree of microglial activation was measured by immuno-fluorescent density of OX-42 ( a microglia marker ) in the substantia nigra ( SN) .The number of viable dopaminergic neurons was determined by counting the tyrosine hydroxylase ( TH) positive neurons in the SN .The behavioral performances were re-vealed with the number of apomorphine-induced rotations , score of forelimb akinesia and vibrissae-elicited forelimb placing a-symmetry.RESULTS:Pretreatment with CoQ10 or intracerebroventricular (icv) posttreatment with minocycline alone pro-vided partial attenuation against MPP +-induced locomotor defects .Integrative therapy provided enhanced beneficial effects , and resulted in a significant attenuation of locomotor disability than any single therapy (all P<0.01).The results of immu-nohistological analysis showed that the TH positive neurons were maximally protected by integrative therapy compared with minocycline group and CoQ 10 group (P<0.01) .CONCLUSION:The integrative therapy of CoQ 10 combined with minocy-cline may offer additional therapeutic benefit to MPP +-induced hemiparkinson rat model .Such neuroprotective strategy of tar-geting different aspect of the neurodegenerative phenotypes may highlight a new therapeutic strategy for future management of PD.

AIM: To explore the effect of brain ischemia injury on cell proliferation and nestin expression in cortex and subependymal zone (SEZ). METHODS: Using a local brain ischemia model(MCAO), BrdU positive cells of cortex and subependymal zone (SEZ), also nestin positive cells, were observed by immunohistochemistry. RESULTS: BrdU and nestin positive cells in SEZ of MCAO rats were obviously increased. In cortex, only nestin positive cells were observed. CONCLUSION: Neural stem cells in SEZ and cortex were activated after brain ischemia, it may be related with neural recovery after brain ischemia injury.

OBJECTIVE: To investigate the potential protective role of Cistanche extracts on 1-methyl-4-phenylpyridinium ion (MPP(+))-induced Parkinson's disease (PD) cellular model, and to find out whether this effect is achieved through the regulation of growth arrest- and DNA damage-induced gene 153 (GADD153). METHODS: MPP(+))-induced cellular injury and the protective effect of Cistanche extracts on the SH-SY5Y cell line viability treated by MPP(+)) were investigated by using methyl thiazolyl tetrazolium (MTT) assay. The mRNA of GADD153 in SH-SY5Y cell line treated by MPP(+)) and Cistanche extracts were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). The protein level of GADD153 in SH-SY5Y was assessed by Western blotting. RESULTS: Cistanche extracts (100 mug/ml) increased the cell viability (P<0.01). And the mRNA of GADD153 in the Cistanche extracts pretreatment group was much less than that in the MPP(+)) group (P<0.01). The result of Western blotting showed that GADD153 had a lower level in the Cistanche extracts pretreatment group, compared with MPP(+)) group, especially in the 100 microg/ml group (P<0.01). CONCLUSION: Cistanche extracts pretreatment has a protective effect on the MPP(+))-treated SH-SY5Y cell line, and its down-regulation of GADD153 may contribute to the effect.

To investigate the protective effects of Naoshuantong, a compound traditional Chinese herbal medicine, on the main components of neurovascular unit in rats with cerebral ischemia/reperfusion injury.