Aim To observe the anti-tumor activity and the mechanism of heparan sulfate proteoglycan(HSPG) on C3H mice transplanted tumors.Methods Tumor model was established and randomly divided into five groups.HSPG groups(5,10,50 mg?kg-1),positive group and control group,intraperitoneal injection was performed once a day for 22 days and the volume of tumors was measured.Mice were treated on 24th day,then tumor weight was examined,thymus index,and spleen index were calculated,the apoptosis was determined by TdT-mediated Dutp nick end labeling(TUNEL) assay in situ,the expression of vascular endothelial growth factor(VEGF) was detected by immunohistochemistry.Results The tumor volume in HSPG groups was reduced without the decrease of thymus index,spleen index.TUNEL assay in situ showed numerous heavy blue apoptosis cells in the HSPG groups significantly higher than in control groups.The tumors in HSPG groups showed significantly lower VEGF expression than those in control group.Conclusion HSPG had significant anti-tumor effects on C3H mice transplantable breast cancer.The mechanisms may be associated with the effects of inducing tumor cell apoptosis and inhibiting the VEGF expression.

Objectives To explore the brain white matter integrity among the patients with buprenorphine tables,scopolamine and promethazine solution(BSP) dependence after abstinence.Methods BSP-dependent patients( n=16)and age/eduction-matched healthy control subjects ( n=18) were assessed by diffusion tensor imaging (DTI) after 3 days,1 month and 2 months of abstinence.White matter (WM) integrity was measured with DTI as fractional anisotropy ( FA),an index of intravoxel orientational coherence of white matter fibers.Results Compared with health controls,FA values were significantly lower in frontal,parietal,temporal and corpus callosum in the BSP addicts after 3-day withdrawal (P＜0.001,uncorrected).Increased FA values in left superior frontal cortex,right medial frontal gyms and fight inferior parietal gyrus were found in BSP users after 2 months of abstinence (P ＜0.001,uncorrected).However,no significant difference was found between these BSP addicts after 1-month abstince.Compared with health controls,BSP dependent subjects still exhibited significantly lower FA in the corpus callosum,frontal,parietal and temporal WM after 2-month withdrawal (P ＜ 0.001,uncorrected ).Conclusion The abnormalities showed less recovery in BSP dependent individuals with abstinence in white matter that suggests that rehabilitation time should be further prolonged for BSP addicts and emphasis cognitive-behavioral therapy to assist BSP abusers rebuild social functions.

Objective To explore what brain regions are modulated by heroin addiction and withdrawal.MethodsWe used functional magnetic resonance imaging to investigate the brain function in 15 heroin-dependent patients 3 days (acute) and 1 month (protracted) after heroin abstinence.Sixteen normal controls were included.Results The blood oxygen level-dependent signal in the orbitofrontal cortex of the brain of heroin-dependent patients was significantly elevated 3 days after the withdrawal.Hyperfunction of the orbitofrontal cortex declined 1 month after the withdrawal.Conclusion Heroin-dependent subjects at both 3 days and 1 month abstinence have persistent abnormalities in the brain function.Although some tangible beneficial effects are noted following 1month of detoxification,possible permanent damage to the brain caused by heroin use is suggested.

Objective To examine white matter integrity in heroin-dependent patients and matched normal controls with diffusion tensor imaging (DTI).Methods The fractional anisotropy was compared between 15 heroin-dependent patients and 15 controls.Results We found the fractional anisotropy was significantly decreased in specific brain regions of the heroin-dependent patients (P ＜ 0.001 uncorrected),including the frontal gyrus,the parietal lobule,the insula,and the corpus callosum.Conclusion The presence of microstructural abnormality is found in the white matter of several brain regions of heroin-dependent patients.

Objective To investigate whether the 5-hydroxytryptamine 2A receptor (5-HT2A)gene T102 C polymorphism is associated with the severity symptoms and negative symptoms in the first episode Chinese Han nationality patients with schizophrenia. Methods Altogether 201 first episode Chinese Han nationality patients with schizophrenia were enrolled in this study. Genotyping of 5-HT2A gene T102 C polymorphism was performed by PCR-RFLP technique. The positive and negative Symptom Scale ( PANSS ) was used for the evaluation of the severity of psychotic symptoms before any drug treat-ment. Results 5-HT2A receptor 102-T/T genotype was significantly associated with both the PANSS total and negative symptom subscale baseline scores before the treatment, but not with the positive and general psychopathology subscales. Conclusion 5-HT2A T102 C functional polymorphism may play a role in negative symptoms and prognosis of Chinese Han nationality people with schizophrenia.

OBJECTIVE To study mechanisms of terguride on the treatment of herion dependence. METHODS Adult male SD rats were randomly assigned into 5 groups: normal control group, saline treatment during heroin use period group, terguride treatment during heroin use period group, saline treatment during heroin reinstatement period group, terguride treatment during heroin reinstatement period group, the last 4 groups established heroin intravenous self administration and cue induced reinstatement models, and after interfernce and perfusion to get the following five brain regions [including ventral tegmental area (VTA)]sections. The expression of dopamine D2 receptor protein and mRNA, prodynorphin protein and preprodynorphin mRNA was detected by immunohistochemistry and hybridization in situ. RESULTS The expression of dopamine D2 receptor was downregulated during heroin use period and upregulated during heroin reinstatement period in nucleus accumbens shell (AcbSH) region, the expression of dopamine D2 receptor mRNA was parallelled with the protein expression approximately, terguride could downregulate the high expression of receptor protein during reinstatement. The expression of dopamine D2 receptor protein and mRNA was upregulated during heroin reinstatement period in central nucleus amygdalae (CeA) region, and terguride could downregulate this high expression. The expression of dopamine D2 receptor protein and mRNA was upregulated during heroin use period and downregulated during heroin reinstatement period in CA1 region of hippocampus and prefrontal cortex (PFC), terguride could downregulate the high expression of mRNA during heroin reinstatement period. The expression of dynorphin protein and mRNA was upregulated during heroin reinstatement period, terguride could downregulate this high expression. The expression of dynorphin protein was upregulated during heroin reinstatement period, and terguride could downregulate this high expression. CONCLUSION The activity of mesolimbic dopamine is boosted up during heroin use period and depressed during reinstatement period, terguride can regulate this dysregulation. The activity of dynorphin is boosted up during cue induced reinstatement, and terguride has the downregulation effect. So the preclinic study demonstrated that terguride has the potential benefit in heroin dependence.

OBJECTIVETo determine the protective effect of pomegranate polyphenols on cardiac function in rats with myocardial ischemia/reperfusion (I/R) injury and explore the possible mechanism.

METHODSFifty SD rats were randomized into 5 equal groups, including a sham-operated group, an I/R model group, and 3 pomegranate polyphenol dose groups (150, 300, and 600 mg/kg). The rats were subject to a 45-min left main coronary artery occlusion followed by a 180-min reperfusion to induce myocardial I/R injury except for the rats those in the sham-operated group. The cardiac functions were monitored continuously during the experiment. At the end of the reperfusion, arterial blood samples were obtained to measure plasma contents of lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA) and the activities of superoxide dismutase (SOD). Triphenyltetrazolium chloride (TTC) staining was used to evaluate the infarct size.

RESULTSCompared with the sham-operated group, all the rats with I/R showed significantly decreased left ventricular systolic pressure (LVSP), maximal rates of increase/decrease of the left ventricular pressure (±dp/dtmax) (P<0.01) and significantly increased left ventricular end-diastolic pressure (LVEDP) (P<0.01). Compared with the I/R model group, all the 3 pomegranate polyphenol groups had significantly improved cardiac function (P<0.05), decreased plasma contents of CK, LDH and MDA (P<0.01), increased SOD activities (P<0.01), and obviously reduced infarct size (P<0.01).

CONCLUSIONPomegranate polyphenols can protect the cardiac function of rats with I/R injury probably in association with their actions in enhancing oxygen free radical scavenging activity and decreasing lipid peroxidative damage of the myocardial tissues.

Animals ; Creatine Kinase ; blood ; Heart ; drug effects ; L-Lactate Dehydrogenase ; blood ; Lipid Peroxidation ; Male ; Malondialdehyde ; blood ; Myocardial Reperfusion Injury ; metabolism ; physiopathology ; Myocardium ; metabolism ; Oxidative Stress ; drug effects ; Polyphenols ; pharmacology ; Punicaceae ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Superoxide Dismutase ; metabolism

OBJECTIVETo determine the expression of connexin 43 (Cx43) protein and explore the functional modulation of gap junction intercellular communication in astrocytes.

METHODSCultured neonatal SD rat astrocytes were divided into normal control group, all-trans retinoic acid (ATRA) group (treated with 10 µmol/L ATRA for 24 h) and oleamide group (treated with 25 µmol/L oleamide for 2 h). Western blotting and immunofluorescence assay were used to detect total cellular Cx43 protein expression and Cx43 expression on the surface of the astrocytes, respectively. Parachute assay was used to evaluate the functional changes of gap junction intercellular communication of the astrocytes.

RESULTSCompared with the normal control cells, ATRA treatment resulted in a significantly increased expression of total Cx43 protein in the astrocytes (P<0.01), and oleamide significantly suppressed its expression (P<0.01). Similarly, ATRA obviously enhanced while oleamide suppressed Cx43 protein expression on the surface of the astrocytes. The gap junction intercellular communication of the astrocytes was enhanced by ATRA (P<0.01) and inhibited by oleamide (P<0.01).

CONCLUSIONATRA and oleamide can modulate gap junction intercellular communication of the astrocytes possibly by regulating the expression of Cx43 protein.

Animals ; Astrocytes ; metabolism ; Cell Communication ; drug effects ; Cells, Cultured ; Connexin 43 ; metabolism ; Gap Junctions ; metabolism ; Oleic Acids ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Tretinoin ; pharmacology

OBJECTIVETo investigate the effect of Src kinase inhibitor PP2 on hypoxia/reoxygenation (H/R) injury in rat astrocytes in vitro.

METHODSIn vitro cultured rat astrocytes were exposed to hypoxia for 8 h followed by reoxygenation for 24 h with or without pretreatment with PP2 (10 µmol/L) for 24 h before H/R injury. MTT assay and flow cytometry were used to detect the viability and apoptosis of the exposed astrocytes, respectively, and the protein expressions of Src, Bax, and Bcl-2 in the cells were determined using Western blotting.

RESULTSPP2 pretreatment significantly increased the viability and decreased the apoptosis rate of rat astrocytes exposed to H/R injury (P<0.01). Western blotting showed that H/R injury caused increased expression of Src kinase, which was lowered by PP2 pretreatment. The ratio of Bax/bcl-2 in the astrocytes increased after H/R injury, and was significantly decreased by PP2 pretreatment (P<0.01).

CONCLUSIONPP2 protects rat astrocytes from H/R injury possibly by inhibiting the expression of Src kinase and activating the anti-apoptotic mechanisms in the cells.

Animals ; Apoptosis ; Astrocytes ; pathology ; Cell Hypoxia ; Cells, Cultured ; Flow Cytometry ; Pyrimidines ; pharmacology ; Rats ; src-Family Kinases ; antagonists & inhibitors

Objective To investigate the effect of Src kinase inhibitor PP2 on hypoxia/reoxygenation (H/R) injury in rat astrocytes in vitro. Methods In vitro cultured rat astrocytes were exposed to hypoxia for 8 h followed by reoxygenation for 24 h with or without pretreatment with PP2 (10 μmol/L) for 24 h before H/R injury. MTT assay and flow cytometry were used to detect the viability and apoptosis of the exposed astrocytes, respectively, and the protein expressions of Src, Bax, and Bcl-2 in the cells were determined using Western blotting. Results PP2 pretreatment significantly increased the viability and decreased the apoptosis rate of rat astrocytes exposed to H/R injury (P<0.01). Western blotting showed that H/R injury caused increased expression of Src kinase, which was lowered by PP2 pretreatment. The ratio of Bax/bcl-2 in the astrocytes increased after H/R injury, and was significantly decreased by PP2 pretreatment (P<0.01). Conclusion PP2 protects rat astrocytes from H/R injury possibly by inhibiting the expression of Src kinase and activating the anti-apoptotic mechanisms in the cells.