Two types of cannabinoid receptors,named cannabinoid receptor 1(CB1) and cannabinoid receptor 2(CB2),have been cloned.CB2 receptors are expressed predominantly in the peripheral immune tissues,but accumulating evidence has revealed that CB2 receptors are also expressed in CNS.Previous studies showed that CB2 agonists can cure and suppress formation of inflammatory and neurophathic pain without central effects after chronic administration.Therefore,they will have good clinical applications in the treatment of pain and neurodegenerative diseases.In this paper,we will review the tissue distribution of CB2 in CNS and pharmacological characteristics of the CB2 agonists have been reviewed.

The homeostasis of extracellular glutamate concentration is critically regulated by glutamate transporters(GTs).Malfunction or decreased expression of GTs has been implicated in the pathogenesis of various nervous system diseases.And among the GTs,glutamate transporter 1(GLT-1)plays a critical role as "glutamate pump".Recent research also finds some GLT-1 variants which alternate C-terminal splicings.Altered expression of proteins encoded by splice variants of GLT-1 has been noted in a number of disease states.Maintaining a physiological range of extracellular glutamate through regulating GTs expression or function may improve some pathological conditions.Many drugs are reported that can regulate GTs.For example,ceftriaxone,phencyclidine,citicoline,riluzole,AKT,thrombosin can up-regulate the expression or function of glutamate transporters;etomidate,clozapine,aspartic acid analogs,endothelin can down-regulate the expression or function of glutamate transporters.In this paper,the drugs which effect GTs will be summarized in order to provide a new insight into the drug design and clinical treatment of neurological diseases.

Objective To investigate rats reared in social isolation as a model of behavioral symptoms of neurodevelop-mental psychiatric disorders including schizophrenia.Methods Male rat pups were housed in individual cages from post-weaning to adulthood.Locomotor activity detection, Morris water maze test and social interaction test were performed. Results Compared with controls, the social isolation-reared rats got more body mass, showed locomotor hyperactivity and increased social interaction, but significant spatial learning changes were not observed in Morris water maze test.Conclu-sion Exposing rats to social isolation can profoundly affect behavior in adulthood, which can be used to build animal mod-els of neurodevelopmental psychiatric disorders including schizophrenia.

Objective To evaluate the efficacy and safety of methylprednisolone in the treatment of children with nephrotic syndrome ,and to observe its adverse reaction .Methods 62 cases with primary nephrotic syndrome were randomly divided into the two groups .32 cases in the treatment group were given methylprednisolone combined with prednisone ,30 cases in the control group were given prednisone therapy .Adreno-corticotropic hormone ( ACTH) and cortisol (Cr) in serum were detected by radioimmunoassay (RIA);plasma albumin,urine protein,creatinine,ala-nine aminotransferase ( ALT) ,blood uric acid were measured by conventional laboratory methods;bone mineral densi-ty was measured by bone mineral density machine .Results The curative effect of complete remission and partial remission between the two groups had no significant difference (χ2 =1.56,P>0.05).After treatment for 10 months, the concentrations of ACTH and Cr between the two groups had no significant differences (t=5.45,P>0.05).After treatment,the contents of plasma albumin in the two groups were (36.5 ±5.5)g/L,(36.7 ±5.9)g/L),the contents of urinary protein in the two groups were (1.5 ±1.1)g/24h,(1.6 ±1.5)g/24h.Before treatment,those in the two groups were albumin (25.7 ±3.3)g/L,(26.3 ±3.5)g/L,urinary protein (5.5 ±3.0)g/24h,(5.8 ±3.5)g/24h, the differences were significant (t=11.45,12.15,all P<0.05);The time of urinary protein changed to negative in the treatment group was 6 days,which was significantly shorter than 8 days in the control group ( Log Rank=10.56, P<0.05);The incidence rate of adverse reactions in the treatment group was 40%(13 cases),which was significantly higher than 26.6%(8 cases) in the control group (χ2 =23.11,P<0.05).Conclusion The combined treatment can shorten the time of urinary protein changed to negative ,but during the treatment ,it may increase adverse reactions in children with primary nephrotic syndrome .

BackgroundCorneal graft reject is a major cause of corneal transplantation failure.Although many immune-suppressing drugs have been utilized to reduce the reject response,their adverse effects on organ and tissue are still insoluble.The tolerance induction of natural killer T (NKT) cells is currently under investigation.However,the study on the application of NKT cells in high risk corneal transplantation is seldom.ObjectiveThe present study was to explore the effects of α-GalCer-activated NKT cella on allografts survival after high-risk corneal transplantation surgery via retro-bubar injection.Methods The lymphocytes were picked up from the spleen of SPF Lewis rats and cultured in RPMI 1640 medium with 100 mg/L α-GalCer.After one week,NKT cells were sorted by the FACSVantage system as CD161+ TCR-α+ cell from the lymphocytes with the cell densities 5×106/ml.Ten SPF Fisher344 rats were used to prepare the donor corneas,and 20 Lewis rats served as recipients.The high risk corneal transplantation models were created by corneal suturing in 20 recipient rats.Penetrating keratoplasty (PKP) was performed in the model rats.0.1 ml NKT cells or the same volume of normal saline solution were retro-bubarly injected at the end of surgery respectively.The corneal allografts were observed and scored based on Holland criteria at the three-day interval under the slit lamp for 30 days.Two weeks after surgery,three rats from each group were sacrificed by excessive anesthesia method and the eyeballs were obtained for histopathological examination.The inflammatory cell infiltration ( CD4+ and CD8+ ) in grafts was evaluated by immunochemistry and flow cytometry.The use of the animals complied with the Statement of ARVO.ResultsThe mean survival time of the allografts was (7.90± 1.37) days in normal saline solution group and (14.70± 1.49) days in NKT cell group,showing a statistically significant difference between the two groups ( t =10.61,P =0.00 ).Two weeks after surgery,all the allografts showed the severe opacity with lots of new blood vessels and edema in normal saline solution group.However,the corneal grafts were clear in NKT cell group.Abundant CD4+ and CD8+T lymphocytes were seen in the allografts in normal saline solution group,but the inflammatory cells were obviously less in NKT cell group.The percentage of NKT cells in the spleen was (5.67±0.25)％ in NKT cell group and ( 1.21±0.19)％ in normal saline solution group ( t =8.43,P =0.00 ).Conclusionsα-GalCer-activated NKT cells can prolong the survival time of allografts in high-risk corneal transplantation.Retro-bubar injection of α-GalCer-activated NKT cells probably is a new approach to the prevention of the rejection of corneal transplantation.

Nuclear factor erythroid-2 related factor 2 ( Nrf2 ) is an important nuclear transcription factor which protects cells a-gainst oxidative stress injury. Upon exposure to reactive oxygen species ( ROS) or electrophilic stress, Nrf2 can translocate into the nucleus, and then bind to the antioxidant response element ( ARE) , regulating the expression of several antioxidant enzymes and phase Ⅱ detoxifying enzymes which aimed at the detoxifica-tion and elimination of harmful exogenous chemicals, resulting in the facilitation of hepatoprotection. Oxidative stress is the com-mon pathogenesis of many liver diseases, while the Nrf2-ARE signaling pathway is extremely important in the prevention and progression of many liver diseases. Nrf2 has more recently been implicated as a new therapeutic target in treating liver diseases. Here, we focus on the most common liver diseases and the devel-opment of these conditions where activation of Nrf2 may alleviate disease progression, so as to provide reference for related re-search in the future.

The investigation on the chemical constituents of Anabasis aphylla L. was carried out by using various chromatographies, such as silica gel, Sephadex LH-20 and RP-C18 column chromatography. Further detailed investigation on the fraction of the ethanol extract of Anabasis aphylla L. yielded one new compound p-acetyl-phenol 1-O-beta-D-xylopyranosyl-(1-->2)-beta-D-glucopyranoside (1), together with five known compounds: piceine (2), isorhamnetin (3), quercetin (4), rutin (5) and isorhamnetin-3-rutinoside (6). Their structures were elucidated by spectral analysis such as NMR and MS. Among these compounds, compounds 2-6 were isolated from this plant for the first time.

This study investigates whether kappa-opioid receptor and ORL1 receptor may interact to form a heterodimer. In immunofluorescence and co-immunoprecipitation experiments, differentially epitope-tagged receptors, colocalization and heterodimerization of kappa-opioid receptor and ORL1 receptor were used and examined in primary culturing rat neurons, Chinese hamster ovary (CHO) or human embryonic kidney 293 (HEK293) cells. The results show that fluorescence of both kappa-opioid receptor and ORL1 receptor were overlapping in primary culturing hippocampal and cortical neurons. Similarly in co-expressing CHO or HEK293 cells, HA-KOR and Myc-ORL1 were almost exclusively confined to the membranes, revealing extensive colocalization. When Flag-KOR and Myc-ORL1 were co-expressing in CHO cells, heterodimerization was identified to have the ability to co-immunoprecipitate ORL1-receptors with kappa-opioid receptor and vice versa. In the current study, further evidence was provided for the direct interaction of two subtypes of opioid receptors, kappa-opioid receptor and ORL1-receptor, to form the heterodimerization. The finding represents the novel pharmacological mechanism for modulation of opioid receptor function as well as diversity of G protein-coupled receptors.

Objective To detect the inhibiting effects of ionizing radiation combined with inhibitors or inducer of autophagy and apoptosis on MCF7 cell line,and to provide the evidence for human breast cancer therapy radiation.Methods MCF7 cells were exposed to X-rays and randomly divided into 4 groups,including 0 Gy,4 Gy,4 Gy+rapamycin,4 Gy+3-MA,and 4 Gy+z-VAD-fmk groups,including 0 Gy,4 Gy,4 Gy+rapamycin,4 Gy+3-MA,and 4 Gy+z-VAD-fmk groups,respectively.The growth doubling time was calculated by MTT method.The specific protein expressions of LC3 autophagy and beclinl were detected by using Western blot and the difference of Drotein contents wasLC3 autophagy and beclinl were detected by using Western blot and the difference of Drotein contents was compared.The percentage of apoptosis of MCF7 cells was measured by flow cytometry (FCM).Resuits The growth doubling time of MCF7 cells in 4 Gy group wag longer than that in O Gy group(t=4.41,P

Aim To investigate the relationship between neuronal nicotinic acetylcholine receptor and the amnesia and hypnosis induced by enflurane in mice.Methods Animal models were established by Intraperitoneal injecting of enflurane(2.2 ml?kg-1 and 0.4 ml?kg-1).Artificial cerebrospinal fluid or different dose of nicotine were intracerebroventricular injected,then sleeping time in the analeptic test was recorded;and the step down latency and error times in the step down test;step through latency and error times in the step through test.For the independent activity test,recorded the independent activity times of mice treated with enflurane(0.4 ml?kg-1) in 5 min.Results Compared with control group,intracerebroventricular nicotine decreased sleeping time in the analeptic test,increased step down latency and step through latency in both step down test and step through test.Furthermore,the error times were decreased in both tests.All the outcomes were significant and the influence was dose-dependent.There was no significant difference for the independent activity times of mice treated with 0.4 ml?kg-1 enflurane by ip injection.Conclusion All the evidence suggested that neuronal nicotinic receptor is one of important targets for the hypnotic and amnestic effect of enflurane in mice.