The catalysis technology of propylene dimerization to form 4-methyl-1-pentene(4MP1)using a Cu-K/K_(2)CO_(3) solid base catalyst is a well-known heterogeneous catalytic reaction.In this study,the intrinsic kinetics of ...The catalysis technology of propylene dimerization to form 4-methyl-1-pentene(4MP1)using a Cu-K/K_(2)CO_(3) solid base catalyst is a well-known heterogeneous catalytic reaction.In this study,the intrinsic kinetics of propylene dimerization were studied in a fixed-bed continuous reactor.Internal and external diffusion during the dimerization reaction experiments were eliminated by adjusting the flow rate of the carrier gas and the particle size of the catalyst support.Then,the concentration changes of each substance at the outlet of the catalyst bed under different residence times were investigated.Moreover,the suitable reaction kinetics equations was derived using the Langmuir Hinshelwood-Hougen-Watson kinetic model.Finally,the activation energy for each reaction involved in the dimerization reaction was calculated.The activation energies of 4MP1,branched by-products,and 1-hexene were 115.0,150.8,and 177.4 kJ/mol,respectively.The effect of process conditions on propylene dimerization with solid base catalysts was studied through kinetic model simulation.By comparing the theoretical values obtained from the simulation with the experimental results,the applicability and accuracy of the kinetic model were verified.展开更多
Objective The neuroprotective effect of erythropoietin (EPO) against 1-methyl-4-phenylpyridinium (MPP^+)- induced oxidative stress in cultured PC12 cells, as well as the underlying mechanism, were investigated. M...Objective The neuroprotective effect of erythropoietin (EPO) against 1-methyl-4-phenylpyridinium (MPP^+)- induced oxidative stress in cultured PC12 cells, as well as the underlying mechanism, were investigated. Methods PC12 ceils impaired by MPP^+ were used as the cell model of Parkinson's disease. Methyl thiazolyl tetrazolium (MTT) was used to assay the viability of the PC12 cells exposed to gradient concentrations of EPO, and the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay was used to analyze the apoptosis ratio of PC 12 cells. The expression of Bcl-2 and Bax in PC 12 cells were examined by Western blot, and the reactive oxygen species (ROS), the mitochondrial transmembrane potential and the activity of caspase-3 in each group were detected by spectrofluorometer. Results Treatment of PC12 cells with MPP^+ caused the loss of cell viability, which may be associated with the elevation in apoptotic rate, the formation of ROS and the disruption of mitochondrial transmembrane potential. It was also shown that MPP+ significantly induced the upregulation of Bax/Bcl-2 ratio and the activation of caspase-3. In contrast, EPO significantly reversed these responses and had the maximum protective effect at 1 U/mL. Conclusion The inhibitive effect of EPO on the MPP^+ -induced cytotoxicity may be ascribed to its anti-oxidative property and anti-apoptotic activity, and EPO may provide a useful therapeutic strategy for treatment of neurodegenerative diseases such as Parkinson's disease.展开更多
New cobalt(II) complex, [Co(O<sub>2</sub>C<sub>15</sub>H<sub>11</sub>N<sub>2</sub>S)<sub>2</sub>(OH<sub>2</sub>)<sub>2</sub>]∙2H<s...New cobalt(II) complex, [Co(O<sub>2</sub>C<sub>15</sub>H<sub>11</sub>N<sub>2</sub>S)<sub>2</sub>(OH<sub>2</sub>)<sub>2</sub>]∙2H<sub>2</sub>O (1∙2H<sub>2</sub>O), has been synthesized upon reaction of cobalt chloride hexahydrate (Co(Cl)<sub>2</sub>∙6H<sub>2</sub>O) with 3-methyl-1-Phenyl-4-(2-thienoyl)-pyrazol-5-one (referred as HL) in ethanol at room temperature. Single crystal X-ray diffraction (XRD), spectroscopic methods, and microelemental analyses were used to characterize 1∙2H<sub>2</sub>O. Compound 1∙2H<sub>2</sub>O crystallizes in the orthorhombic crystal system with a Pbca space group and with the cobalt atom being pseudo-octahedral coordinated. The broth microdilution technique was used to screen the free ligand (HL) and the complex (1∙2H<sub>2</sub>O) for antimicrobial activities. HL has a low activity (MIC > 100 μg/mL) on all microorganisms, whereas compound 1∙2H<sub>2</sub>O displayed moderate activity (10 ∙2H<sub>2</sub>O exhibited bactericidal and fungicidal activity respectively on all the bacteria and yeasts tested. These findings reveal that the antimicrobial activity of HL was enhanced upon coordination to Co(II) ion against all microorganisms (bacteria and fungus).展开更多
New cobalt(II) complex, [Co(O<sub>2</sub>C<sub>15</sub>H<sub>11</sub>N<sub>2</sub>S)<sub>2</sub>(OH<sub>2</sub>)<sub>2</sub>]∙2H<s...New cobalt(II) complex, [Co(O<sub>2</sub>C<sub>15</sub>H<sub>11</sub>N<sub>2</sub>S)<sub>2</sub>(OH<sub>2</sub>)<sub>2</sub>]∙2H<sub>2</sub>O (1∙2H<sub>2</sub>O), has been synthesized upon reaction of cobalt chloride hexahydrate (Co(Cl)<sub>2</sub>∙6H<sub>2</sub>O) with 3-methyl-1-Phenyl-4-(2-thienoyl)-pyrazol-5-one (referred as HL) in ethanol at room temperature. Single crystal X-ray diffraction (XRD), spectroscopic methods, and microelemental analyses were used to characterize 1∙2H<sub>2</sub>O. Compound 1∙2H<sub>2</sub>O crystallizes in the orthorhombic crystal system with a Pbca space group and with the cobalt atom being pseudo-octahedral coordinated. The broth microdilution technique was used to screen the free ligand (HL) and the complex (1∙2H<sub>2</sub>O) for antimicrobial activities. HL has a low activity (MIC > 100 μg/mL) on all microorganisms, whereas compound 1∙2H<sub>2</sub>O displayed moderate activity (10 ∙2H<sub>2</sub>O exhibited bactericidal and fungicidal activity respectively on all the bacteria and yeasts tested. These findings reveal that the antimicrobial activity of HL was enhanced upon coordination to Co(II) ion against all microorganisms (bacteria and fungus).展开更多
1-methyl-4-phenylpyridinium ion (MPP^+) induces endoplasmic reticulum stress and activates caspase-12 in PC12 cells, leading to neuronal apoptosis. However, the underlying molecular mechanism remains unknown. The p...1-methyl-4-phenylpyridinium ion (MPP^+) induces endoplasmic reticulum stress and activates caspase-12 in PC12 cells, leading to neuronal apoptosis. However, the underlying molecular mechanism remains unknown. The present study investigated the regulatory effects of nerve growth factor (Akt activator) and lithium chloride (glycogen synthase kinase-3β inhibitor) on the endoplasmic reticulum stress signaling pathway. The results revealed that MPP+ induced expression of Bip and C/EBP homologous protein. The upregulation of Bip and C/EBP homologous protein, as well as the decreased pro-caspase-12 level induced by MPP^+ were inhibited by pretreatment of the nerve growth factor or lithium chloride. These results suggest that the phosphatidylinositol 3 kinase-Aktglycogen synthase kinase-3β pathway is involved in MPP-induced endoplasmic reticulum stress.展开更多
BACKGROUND: Insulin receptor (IR) expression in the substantia nigra of patients with Parkinson disease (PD) is not only significantly lower than that in the substantia nigra of normal persons of the same age, bu...BACKGROUND: Insulin receptor (IR) expression in the substantia nigra of patients with Parkinson disease (PD) is not only significantly lower than that in the substantia nigra of normal persons of the same age, but also significantly lower than that in other regions in brain of himself/herself. It suggests that the abnormal effect of insulin receptor-mediated insulin, as a neurotrophic factor, is very possibly related to the loss of dopaminergic neurons in the substantia nigra and striatum in patients with Parkinson disease. OBJECTIVE : TO observe the interventional effect of insulin on 1-methyl-4-phenylpyridinium ion (MPP^+)-induced apoptosis of PC12. DESIGN: Controlled observation SETTINGS: Department of Neurology, Beijing China-Japan Friendship Hospital; Department of Neurology Huashan Hospital Affiliated to Fudan University. MATERIALS: PC12 cells were provided by the Cell Bank, Shanghai Institute of Cell Biology, Chinese Academy of Science. MPP^+, MTT, HOECHST 33258 (Invitrogen Life Technologies), reverse transcription-polymerase chain reaction (RT-PCR) reagent (Takara Shuzo Co., Ltd.), flow cytometer (Bacton Dickionson, San Jose, CA), enzyme labelling instrument (Bio-Tek, Winooski, VT) and PCR circulation instrument (Takara Shuzo Co., Ltd) were used in this study. METHODS : This study was carried out in the Department of Neurology, Huashan Hospital Affiliated to Fudan University during June 2003 to August 2004. (1) Cell culture and experimental grouping: PC12 cells were cultured according to the method from Peng et al, then were randomized into 3 groups; blank control group, MPP^+ group and insulin group. (2) Detection of relative survival rate of cells: The relative survival rate of cells at different MPP^+ final concentrations (0, 50, 100, 200, 300, 1 000 μmol/L) and at different culture time (0, 4, 8, 12, 18, 24 hours) in the 300 Fmol/L MPP^+ group and different concentrations of insulin (0, 15, 50, 100 nmol/L) in the insulin group was detected with MTT method according to the method from Hansen et al. (3) Observation of cell apoptosis: After stained by HOECHST 33258, the apoptotic cells were observed under the fluorescence miscroscope with the method from Chen et al. (4) Dection of apoptotic rate of cells: Apoptotic rate of cells was detected with flow cytometry according to the method from Zhang et al. (5) The expression of tyrosine hydroxylase (TH) mRNA in PC12 cells was detected with RT-PCR methods according to the modified method from Peng et al. MAIN OUTCOME MEASURES : Comparison of relative survival rate, apoptosis rate, the expression of IR mRNA and TH mRNA and cell apoptosis. RESULTS: (1) After 12-hour incubation of 100, 200, 300 and 1 000 μmol/L MPP^+, the relative survival rate of PC12 cells was (72.88±2.91)%, (60.64±0.81)%, (54.56±0.76)% and (16.89±2.83)%, respectively, which was significantly lower than that of blank control group (100%, P 〈 0.05); After 12, 18 and 24-hour incubation, the relative survival rate of PC12 cells was (54.56±0.76)%, (42.43±0.16)% and (23.56±0.17)% respectively, which was significantly lower than that of blank control group (100%, P〈 0.05); When 15, 50 and 100 nmol/L insulin was pre-added to cells, the relative survival rate was (70.10±0.16)%, (78.01 ±2.43)% and (83.55±1.43)%, respectively, which was significantly higher than MPP^+ alone [(54.56±0.76)%, P 〈 0.05]. (2) Appototic bodies were rarely seen in the blank control group, but densely gathered in the MPP^+ group and were significantly decreased in the insulin group. (3) Apoptosis rate of PC12 cells in the MPP^+ group was significantly higher than that in the blank control group [(36.56±0.89)% vs. (2.34±0.23)%, P〈 0.05], and that in the 15, 50, 100 nmol/L insulin group [(30.01±0.04)%, (24.23±0.37)%, (20.01 ±1.01)%, respectivelyl was significantly lower than that in MPP^+ group (P 〈 0.05). (4) The TH mRNA expression in PC12 cells in MPP^+ group was significantly lower than that in blank control group; The expression of TH mRNA in insulin group was gradually increased in an insulin dose-dependent manner. There were no significant changes in the expression of IR mRNA under different experimental conditions. CONCLUSION: Insulin can resist MPP^+-induced apoptosis of PC12 cells, lessen the damage of PC12 cells, but does not change the gene expression of target cell insulin receptor.展开更多
Objective: To explore the protective effect of minocycline on the apoptosis of cellular parkinsonism models induced by MPP^+ . Methods: Using PC12 cells as the apoptotic model of dopaminergic neurons, MC and MPP^+...Objective: To explore the protective effect of minocycline on the apoptosis of cellular parkinsonism models induced by MPP^+ . Methods: Using PC12 cells as the apoptotic model of dopaminergic neurons, MC and MPP^+ were added into the culture medium of PC12 cells, and using MTr to assay the cell viability and metabolic state; The cells apoptosis was assayed by electrophoresis method and using flow cytometry FACS to assay the apoptosis ratio. Results: Added the MPP^+ to get the concentration of 10μmol/L, the cellular parkinsonism model of apoptosis had been prepared. The pre-treatment of MC ( 100/μmol/L) could significantly increase the PC12 cell viability. The apoptosis ratio of MC+MPP^+ group was significantly lower than that of MPP^+ group, but was still significantly higher than that of control group. Conclusion: MC may protect the cell apoptosis induced by MPP^+ to some extent.展开更多
Apoptosis and viability of PC12 cells following 1-methyl-4-phenylpyridinium ion (MPP+)-induced injury were monitored by flow cytometry, following Annexin V-propidium iodide double labeling, and 3-(4,5-Dimethylthia...Apoptosis and viability of PC12 cells following 1-methyl-4-phenylpyridinium ion (MPP+)-induced injury were monitored by flow cytometry, following Annexin V-propidium iodide double labeling, and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, respectively. The release of lactate dehydrogenase, superoxide dismutase activity and levels of malondialdehyde were determined by UV spectrophotometry. The changes in mitochondrial membrane potential and the intracellular concentration of calcium were determined by flow cytometry, and the activity of caspase-3 was monitored by western blot. According to cell viability and apoptosis studies, MPP+-induced apoptosis in PC12 cells was inhibited in the presence of 10 tJg/mL of Eleutheroside B Our results indicate that the neuroprotective effect of Eleutheroside B, following MPP+-induced apoptosis in PC12 cells, involves increasing the anti-oxidative stress capacity of cells, maintaining the high-energy state of mitochondrial membrane potential, reducing intracellular calcium concentration and inhibiting caspase-3 activity.展开更多
The extraction behavior of rare earths was studied by using paraffin with ceresin as a diluent containing 1-phenyl-3-methyl-4-benzoyl-pyrazolone-5.In solid phase,the composition of complexes is REP_3.The equilib- rium...The extraction behavior of rare earths was studied by using paraffin with ceresin as a diluent containing 1-phenyl-3-methyl-4-benzoyl-pyrazolone-5.In solid phase,the composition of complexes is REP_3.The equilib- rium extraction constants and pH_(1/2) values of solid-liquid extraction are higher than those of normal liquid-liquid extraction.The extraction efficiency tends to maximum when the ratio of phases is 1:1.When the extraction temperature is higher than the melting point of paraffin and the extraction time is over 10 min,the extraction efficiency keeps constant.Moreover,the relationship among separation factor,equilibrium extrac- tion constant,pH_(1/2) value and atomic number was obtained.The mechanism of solid-liquid extraction is analogous to that of liquid-liquid extraction.展开更多
BACKGROUND: To date, a complete protein expression profile of the midbrain substantia nigra in a mouse model of chronic Parkinson's disease, induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), does ...BACKGROUND: To date, a complete protein expression profile of the midbrain substantia nigra in a mouse model of chronic Parkinson's disease, induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), does not exist. In addition, there are no reports of analysis of differential protein expression. OBJECTIVE: To separate and evaluate MPTP-induced differential protein expression through the use of proteomics in the substantia nigra of a mouse model of chronic Parkinson's disease. DESIGN: Randomized controlled animal study. SETTING: Department of Neurology, the First Affiliated Hospital, Chongqing Medical University. MATERIALS: Sixteen 8-10-week old, healthy, male, C57BL mice, weighing 20-25 g, and of clean grade, were provided by the Experimental Animal Center of Chongqing Medical University. The experimental animals were disposed according to ethical criteria. MPTP was provided by Sigma Company, USA; Pdquest 2D image analysis software and gelatum/irradiance image analysis system (ChemiDoc XRS) by Bio-Rad, USA; and Voyager DE-PROMALD1-TOF-MS mass spectroscopy analyzer by AB1 Company, USA. METHODS: This study was performed in Chongqing Neurological Laboratory between November 2006 and July 2007. Mice were randomly divided into model and control groups, with 8 mice in each group. Mice in the model group were received a subcutaneous injection of MPTP (25 mg&g), twice a week, for five successive weeks, to establish a chronic Parkinson's disease model. Mice in the control group received the same volume of a subcutaneous saline injection at the same time points. Mice were sacrificed by anesthesia to rapidly obtain the midbrain for protein separation of the substantia nigra. MAIN OUTCOME MEASURES: (1) 2-ED handbook (Bio-Rad Company) was referenced for two-dimensional electrophoresis, (2) PDQUEST8,0 analytical electrophoresis pattern was adopted to evaluate differential protein expression. (3) Peptide mass finger print map and data were retrieved on http://www.prospector.ucsf.edu to compare differential substantia nigral protein expression in the two groups. RESULTS: Two-dimensional gel electrophoresis of substantia nigra tissue indicated that there were 33 differential protein expressions between the two groups. Three new proteins were evaluated, including α -enolase, which exhibited regulated expression, tumor necrosis factor ligand superfamily member 4, and cyclin-dependent kinase inhibitor 1B. CONCLUSION: There are three proteins that exhibit differential expression in the substantia nigra- α -enolase, tumor necrosis factor ligand superfamily member 4, and cyclin-dependent kinase inhibitor 1B.展开更多
Poly(4-methyl-1-pentene) (PMP) hollow fiber membranes were prepared by the melt-spun and cold-stretch(MSCS) method. Scanning electronic microscopy (SEM) was used to characterize the section and surface structures of t...Poly(4-methyl-1-pentene) (PMP) hollow fiber membranes were prepared by the melt-spun and cold-stretch(MSCS) method. Scanning electronic microscopy (SEM) was used to characterize the section and surface structures of themembranes with special asymmetric structure. The preliminary results of gas permeation measurements indicated that the resultant hollow fiber membranes have the potential ability for oxygen/nitrogen separation.展开更多
The title compound trans-4-[(5-(2,4-dichlorophenoxy)-3-methyl- 1-phenyl-1H-pyrazol-4-yl)methyleneamino]- 1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one 3 (C28H23Cl2N5O2, Mr = 532.41) has been synthesized and its...The title compound trans-4-[(5-(2,4-dichlorophenoxy)-3-methyl- 1-phenyl-1H-pyrazol-4-yl)methyleneamino]- 1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one 3 (C28H23Cl2N5O2, Mr = 532.41) has been synthesized and its crystal structure was determined by single-crystal X-ray diffraction analysis. It crystallizes in triclinic, space group P1- with a = 8.9438(4), b = 11.6065(5), c = 14.2215(6)A, α = 112.566(1), β = 92.324(2), γ = 102.91(1)°, V= 1315.65(10) A^3, Z = 2, Dc = 1.344 g/cm^3,μ(MoKa) = 0.282 mm^-1, λ = 0.71073 A, F(000) = 552, the final R = 0.0587 and wR = 0.1578 for 5071 observed reflections (I 〉 2σ(I)). X-ray analysis reveals that the product is a thermodynamically stable trans isomer. Intra- and intermolecular C( 12)-H(12)…O(1) and C(28)-H(28)...O(1)# 1 hydrogen bonds were observed in the title compound.展开更多
The crystal structure of the title compound ethyl 3-(4-chlorophenyl)-3,4-dihydro-6- methyl-4-oxo-2-(pyrrolidin-1-yl)furo[2,3-d]pyrimidine-5-carboxylate (C20H20ClN3O4, Mr= 401.84) has been prepared and determined...The crystal structure of the title compound ethyl 3-(4-chlorophenyl)-3,4-dihydro-6- methyl-4-oxo-2-(pyrrolidin-1-yl)furo[2,3-d]pyrimidine-5-carboxylate (C20H20ClN3O4, Mr= 401.84) has been prepared and determined by single-crystal X-ray diffraction. The crystal is of monoclinic, space group P21/n with a = 20.6215(9), b = 8.5311(4), c = 21.6886(9) A^°, β = 91.607(1)°, V = 3814.0(3)A^°^3, Z = 8, Dc = 1.400 g/cm^3, F(000) = 1680, μ = 0.233 mm^-1, R = 0.0718 and wR = 0.1545 for 6717 observed reflections with I 〉 2σ(I). X-ray diffraction analysis reveals two crystallographically independent molecules in the asymmetric unit.展开更多
Microglia-mediated neuroinflammation is considered a pathological feature of Parkinson's disease.Triggering receptor expressed on myeloid cell-1(TREM-1)can amplify the inherent immune response,and crucially,regula...Microglia-mediated neuroinflammation is considered a pathological feature of Parkinson's disease.Triggering receptor expressed on myeloid cell-1(TREM-1)can amplify the inherent immune response,and crucially,regulate inflammation.In this study,we found marked elevation of serum soluble TREM-1 in patients with Parkinson's disease that positively correlated with Parkinson's disease severity and dyskinesia.In a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease,we found that microglial TREM-1 expression also increased in the substantia nigra.Further,TREM-1 knockout alleviated dyskinesia in a mouse model of Parkinson's disease and reduced dopaminergic neuronal injury.Meanwhile,TREM-1 knockout attenuated the neuroinflammatory response,dopaminergic neuronal injury,and neutrophil migration.Next,we established an in vitro 1-methyl-4-phenyl-pyridine-induced BV2 microglia model of Parkinson's disease and treated the cells with the TREM-1 inhibitory peptide LP17.We found that LP17 treatment reduced apoptosis of dopaminergic neurons and neutrophil migration.Moreover,inhibition of neutrophil TREM-1 activation diminished dopaminergic neuronal apoptosis induced by lipopolysaccharide.TREM-1 can activate the downstream CARD9/NF-κB proinflammatory pathway via interaction with SYK.These findings suggest that TREM-1 may play a key role in mediating the damage to dopaminergic neurons in Parkinson's disease by regulating the interaction between microglia and peripheral neutrophils.展开更多
Several cyclopropanation catalysts for the synthesis of 3(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylates have been studied in this paper. Owing to electron deficiency of 1,1-dichloro-4-methyl-1,3-pentadiene, ...Several cyclopropanation catalysts for the synthesis of 3(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylates have been studied in this paper. Owing to electron deficiency of 1,1-dichloro-4-methyl-1,3-pentadiene, yield of this reaction is rather law compared with that of 2,5-dimethyl-2,4-pentadiene, Of all catalysts concerned. yield ranged from 25.1% to 47.2%.展开更多
Two new Schiff bases based on 5-chloro-3-methyl-1-phenyl-1 H-pyrazole-4-carbaldehyde, namely, N-((5-chloro-3-methyl-1-phenyl-1 H-pyrazol-4-yl)methylene)-4-morpholinoaniline(Ⅲa) and N-((5-chloro-3-methyl-1-phenyl-1 H-...Two new Schiff bases based on 5-chloro-3-methyl-1-phenyl-1 H-pyrazole-4-carbaldehyde, namely, N-((5-chloro-3-methyl-1-phenyl-1 H-pyrazol-4-yl)methylene)-4-morpholinoaniline(Ⅲa) and N-((5-chloro-3-methyl-1-phenyl-1 H-pyrazol-4-yl)methylene)-3-fluoro-4-morpholinoaniline(Ⅲb), were synthesized and characterized by IR, LC-MS, 1 H NMR and 13 C NMR spectroscopy. Meanwhile, the three-dimensional configurations of the two title compounds were further characterized by single-crystal X-ray diffraction analyses. Both the compounds are thermodynamically stable trans-isomers. Moreover, the fluorescence properties and antioxidant activities against DPPH of the two target compounds have been investigated, and the results showed that the title compounds both have fluorescence performance and certain antioxidant activities against DPPH radical.展开更多
At present, pathogenesis and mechanism of Parkinson disease (PD) are still unclear. Animal models of PD are essential tools in studies on etiology and therapy and should mimic the chronic pathological process, histo...At present, pathogenesis and mechanism of Parkinson disease (PD) are still unclear. Animal models of PD are essential tools in studies on etiology and therapy and should mimic the chronic pathological process, histological characteristics and motor behavior dysfunction. In recent years, transgenic mice have been widely utilized to study the mechanism of PD, and it has become imperative that a PD mouse model of motor behavioral dysfunction be established. OBJECTIVE: To compare the behavioral and histochemical characters of two neurotoxic mice model induced with 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenyl-1, 2, 3, 6 -tetrahydropyridine (MPTP), and a better method to mimic Parkinson disease will be found out. DESIGN: Parallel experiment. SETTING: Laboratory of Molecular Genetics, Department of Medical Genetics, Shanghai Jiao Tohg University. MATERIALS: Sixty 129Sv/C57BL6J male wild mice, SPF grade, 8 - 12 weeks old, weighing 20 - 25 g, were provided by Experimental Animal Center, Shanghai Jiao Tong University. All the surgery operation was performed according to the rules of Shanghai Jiaotong University Animal Committee. METHODS: The experiment was carried out in the Laboratory of Molecular Genetics (National Key Laboratory), Department of Medical Genetics, Shanghai Jiao Ttong University from March to August 2006. ①Thirty-two male mice were randomly divided into control group and drug treatment group with 16 mice in each group. Surgery was carried out and 6-OHDA was administrated to substantia nigra pars compacta (SNpc) and nigra-striatum pathway according to the different parameters with intoxication apparatus. Saline was injected to the other 16 mice according to the same paradigm. 1 mg/kg apomorphine was injected intraperitoneally 2 weeks later after surgery to induce the imbalanced rotation behavior for 40 minutes. ②Twenty-eight mice were randomly divided into 4 groups with 7 in each group, including low-dose, moderate-dose, high-dose groups and negative control group. Then, mice in the drug treatment group were injected intraperitoneally with 5, 10 and 15 mg/kg MPTP for 9 successive days. In addition, mice in the control group were injected with the same volume of saline for 9 days. Pole test and stride length test were utilized to detect coordinative behavioral dysfunction. Mice were sacrificed 20 days after MPTP treatment, and histochemical staining of tyrosine hydroxynase (TH) was used to observe the loss of dopaminergic neuron in SNpc. MAIN OUTCOME MEASURES: ① Success ratio of each model establishment method; ② inducible asymmetric cycle behavior test 2 weeks after 6-OHDA injection; ③behavioral dysfunction in pole test and stride length, morphological changes in brain tissue. RESULTS: Totally sixty mice were used in this experiment and 3 mice were excluded because of the hypersensitivity or the clumsy reaction in motor behavioral detection before MPTP treatment, therefore, data was analyzed with the rest 57 mice. ① Lethal ratio: Three out of 16 mice died in striatum injection group and 5 out of 16 mice died in nigro-striatal pathway group. No mouse died in MPTP treatment groups. ② Locomotor behavior: No dysfunction of locomotor was found in 6-OHDA treatment groups. However, several motor behavioral dysfunction were start to present at the 4th day of MPTP injection. ③ Asymmetric cycle behavior: No asymmetric cycle was induced successfully two weeks after 6-OHDA surgery. Mice show hypersensitive behavior 10 minutes after apomorphine injection, which lasted for about 20 minutes. ④ Pole test: From the 4^th day of MPTP treatment, mice started to display coordinate dysfunction, such as climbing down along the pole in spiral, moving slowly with hesitation. Some mice could not grab the pole and slide down along the pole at 4th day post injection. Comparing with 0 dose control group, all the threedrug treatment groups show significant different dysfunction from the 4th day to the 20th day post injection (P 〈 0.01). ⑤ stride length test: Mice's stride length decreased, when treated with MPTP, and the mice in the high dose group displayed obviously. ⑥ Dopaminergic neuron stained with TH in nigra pars compacta: The results indicated that administrated MPTP (from low dose to high dose) by intraperitoneal cause chronic lesions on the dopaminergic neuron in the SNpc. CONCLUSION: PD mice models induced with 6-OHDA show high mortality ratio and no asymmetric cycle was found after apomorphine injection. However, injection of MPTP intraperitoneally can simulate the chronic pathway of PD, typical histological changes are found and stable motor behavioral dysfunctions are displayed.展开更多
BACKGROUND : To summarize the metabolic pathway of 1-methyl-4-phenyl-1,2,3,6-tetradropyridine (MPTP) and its mechanism in inducing Parkinson disease. DATA SOURCES: A computer-based online search of Medline databas...BACKGROUND : To summarize the metabolic pathway of 1-methyl-4-phenyl-1,2,3,6-tetradropyridine (MPTP) and its mechanism in inducing Parkinson disease. DATA SOURCES: A computer-based online search of Medline database was undertaken to identify articles about the metabolic pathway of MPTP and its mechanism in inducing Parkinson disease published in English between January 1996 and August 2004, the keywords were "MPTP, Parkinson disease". Meanwhile, Chinese relevant articles published between January 2000 and August 2004 were searched in Wanfang database with the keywords of "MPTP, Parkinson disease". STUDY SELECTION: More than 300 relevant literatures were retrieved, and the full-texts were further searched, those about the establishment of animal models, molecular mechanism of MPTP neurotoxicity and the metabolism were selected, and the obviously repetitive ones, case report and reviews were excluded, finally 18 of them were selected for summarization. DATA EXTRACTION: The 18 literatures were categorized according to MPTP induced animal models of Parkinson disease, mechanism of MPTP in inducing apoptosis in models of Parkinson disease, role of dopamine in the neurotoxic mechanism of MPTP, the role of reactive oxygen species and nitric oxide in the neurotoxicity of MPTP. DATA SYNTHESIS: Animal models of Parkinson disease induced by MPTP can not only produce the clinical characters of Parkinson disease, also duplicate the main biochemical and pathological changes of Parkinson disease. The metabolic pathway of MPTP and its mechanism in inducing Parkinson disease included producing free oxygen and nitric oxide, damaging mitochondrial respiratory chain, and inducing apoptosis, etc. which could all lead to the degeneration and loss of dopaminergic neurons. CONCLUSION : Although some aspects of the models of Parkinson disease are different from that in human beings, we can still know the neurodegeneration of Parkinson disease through studying the molecular mechanism of MPTP.展开更多
基金supported by the National Natural Science Foundation of China under agreement number 22378026the Project of Construction of Innovative Teams and Teacher Career Development for Universities and Colleges under Beijing Municipality(IDHT20180508).
文摘The catalysis technology of propylene dimerization to form 4-methyl-1-pentene(4MP1)using a Cu-K/K_(2)CO_(3) solid base catalyst is a well-known heterogeneous catalytic reaction.In this study,the intrinsic kinetics of propylene dimerization were studied in a fixed-bed continuous reactor.Internal and external diffusion during the dimerization reaction experiments were eliminated by adjusting the flow rate of the carrier gas and the particle size of the catalyst support.Then,the concentration changes of each substance at the outlet of the catalyst bed under different residence times were investigated.Moreover,the suitable reaction kinetics equations was derived using the Langmuir Hinshelwood-Hougen-Watson kinetic model.Finally,the activation energy for each reaction involved in the dimerization reaction was calculated.The activation energies of 4MP1,branched by-products,and 1-hexene were 115.0,150.8,and 177.4 kJ/mol,respectively.The effect of process conditions on propylene dimerization with solid base catalysts was studied through kinetic model simulation.By comparing the theoretical values obtained from the simulation with the experimental results,the applicability and accuracy of the kinetic model were verified.
文摘Objective The neuroprotective effect of erythropoietin (EPO) against 1-methyl-4-phenylpyridinium (MPP^+)- induced oxidative stress in cultured PC12 cells, as well as the underlying mechanism, were investigated. Methods PC12 ceils impaired by MPP^+ were used as the cell model of Parkinson's disease. Methyl thiazolyl tetrazolium (MTT) was used to assay the viability of the PC12 cells exposed to gradient concentrations of EPO, and the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay was used to analyze the apoptosis ratio of PC 12 cells. The expression of Bcl-2 and Bax in PC 12 cells were examined by Western blot, and the reactive oxygen species (ROS), the mitochondrial transmembrane potential and the activity of caspase-3 in each group were detected by spectrofluorometer. Results Treatment of PC12 cells with MPP^+ caused the loss of cell viability, which may be associated with the elevation in apoptotic rate, the formation of ROS and the disruption of mitochondrial transmembrane potential. It was also shown that MPP+ significantly induced the upregulation of Bax/Bcl-2 ratio and the activation of caspase-3. In contrast, EPO significantly reversed these responses and had the maximum protective effect at 1 U/mL. Conclusion The inhibitive effect of EPO on the MPP^+ -induced cytotoxicity may be ascribed to its anti-oxidative property and anti-apoptotic activity, and EPO may provide a useful therapeutic strategy for treatment of neurodegenerative diseases such as Parkinson's disease.
文摘New cobalt(II) complex, [Co(O<sub>2</sub>C<sub>15</sub>H<sub>11</sub>N<sub>2</sub>S)<sub>2</sub>(OH<sub>2</sub>)<sub>2</sub>]∙2H<sub>2</sub>O (1∙2H<sub>2</sub>O), has been synthesized upon reaction of cobalt chloride hexahydrate (Co(Cl)<sub>2</sub>∙6H<sub>2</sub>O) with 3-methyl-1-Phenyl-4-(2-thienoyl)-pyrazol-5-one (referred as HL) in ethanol at room temperature. Single crystal X-ray diffraction (XRD), spectroscopic methods, and microelemental analyses were used to characterize 1∙2H<sub>2</sub>O. Compound 1∙2H<sub>2</sub>O crystallizes in the orthorhombic crystal system with a Pbca space group and with the cobalt atom being pseudo-octahedral coordinated. The broth microdilution technique was used to screen the free ligand (HL) and the complex (1∙2H<sub>2</sub>O) for antimicrobial activities. HL has a low activity (MIC > 100 μg/mL) on all microorganisms, whereas compound 1∙2H<sub>2</sub>O displayed moderate activity (10 ∙2H<sub>2</sub>O exhibited bactericidal and fungicidal activity respectively on all the bacteria and yeasts tested. These findings reveal that the antimicrobial activity of HL was enhanced upon coordination to Co(II) ion against all microorganisms (bacteria and fungus).
文摘New cobalt(II) complex, [Co(O<sub>2</sub>C<sub>15</sub>H<sub>11</sub>N<sub>2</sub>S)<sub>2</sub>(OH<sub>2</sub>)<sub>2</sub>]∙2H<sub>2</sub>O (1∙2H<sub>2</sub>O), has been synthesized upon reaction of cobalt chloride hexahydrate (Co(Cl)<sub>2</sub>∙6H<sub>2</sub>O) with 3-methyl-1-Phenyl-4-(2-thienoyl)-pyrazol-5-one (referred as HL) in ethanol at room temperature. Single crystal X-ray diffraction (XRD), spectroscopic methods, and microelemental analyses were used to characterize 1∙2H<sub>2</sub>O. Compound 1∙2H<sub>2</sub>O crystallizes in the orthorhombic crystal system with a Pbca space group and with the cobalt atom being pseudo-octahedral coordinated. The broth microdilution technique was used to screen the free ligand (HL) and the complex (1∙2H<sub>2</sub>O) for antimicrobial activities. HL has a low activity (MIC > 100 μg/mL) on all microorganisms, whereas compound 1∙2H<sub>2</sub>O displayed moderate activity (10 ∙2H<sub>2</sub>O exhibited bactericidal and fungicidal activity respectively on all the bacteria and yeasts tested. These findings reveal that the antimicrobial activity of HL was enhanced upon coordination to Co(II) ion against all microorganisms (bacteria and fungus).
基金the National Natural Science Foundation of China, No. 30860085a grant from the Candidates of Young and Middle-Aged Academic Leaders of Yunnan Province, No. 2006PY01-07the Natural Science Foundation of Yunnan Province, No. 2007C177M
文摘1-methyl-4-phenylpyridinium ion (MPP^+) induces endoplasmic reticulum stress and activates caspase-12 in PC12 cells, leading to neuronal apoptosis. However, the underlying molecular mechanism remains unknown. The present study investigated the regulatory effects of nerve growth factor (Akt activator) and lithium chloride (glycogen synthase kinase-3β inhibitor) on the endoplasmic reticulum stress signaling pathway. The results revealed that MPP+ induced expression of Bip and C/EBP homologous protein. The upregulation of Bip and C/EBP homologous protein, as well as the decreased pro-caspase-12 level induced by MPP^+ were inhibited by pretreatment of the nerve growth factor or lithium chloride. These results suggest that the phosphatidylinositol 3 kinase-Aktglycogen synthase kinase-3β pathway is involved in MPP-induced endoplasmic reticulum stress.
文摘BACKGROUND: Insulin receptor (IR) expression in the substantia nigra of patients with Parkinson disease (PD) is not only significantly lower than that in the substantia nigra of normal persons of the same age, but also significantly lower than that in other regions in brain of himself/herself. It suggests that the abnormal effect of insulin receptor-mediated insulin, as a neurotrophic factor, is very possibly related to the loss of dopaminergic neurons in the substantia nigra and striatum in patients with Parkinson disease. OBJECTIVE : TO observe the interventional effect of insulin on 1-methyl-4-phenylpyridinium ion (MPP^+)-induced apoptosis of PC12. DESIGN: Controlled observation SETTINGS: Department of Neurology, Beijing China-Japan Friendship Hospital; Department of Neurology Huashan Hospital Affiliated to Fudan University. MATERIALS: PC12 cells were provided by the Cell Bank, Shanghai Institute of Cell Biology, Chinese Academy of Science. MPP^+, MTT, HOECHST 33258 (Invitrogen Life Technologies), reverse transcription-polymerase chain reaction (RT-PCR) reagent (Takara Shuzo Co., Ltd.), flow cytometer (Bacton Dickionson, San Jose, CA), enzyme labelling instrument (Bio-Tek, Winooski, VT) and PCR circulation instrument (Takara Shuzo Co., Ltd) were used in this study. METHODS : This study was carried out in the Department of Neurology, Huashan Hospital Affiliated to Fudan University during June 2003 to August 2004. (1) Cell culture and experimental grouping: PC12 cells were cultured according to the method from Peng et al, then were randomized into 3 groups; blank control group, MPP^+ group and insulin group. (2) Detection of relative survival rate of cells: The relative survival rate of cells at different MPP^+ final concentrations (0, 50, 100, 200, 300, 1 000 μmol/L) and at different culture time (0, 4, 8, 12, 18, 24 hours) in the 300 Fmol/L MPP^+ group and different concentrations of insulin (0, 15, 50, 100 nmol/L) in the insulin group was detected with MTT method according to the method from Hansen et al. (3) Observation of cell apoptosis: After stained by HOECHST 33258, the apoptotic cells were observed under the fluorescence miscroscope with the method from Chen et al. (4) Dection of apoptotic rate of cells: Apoptotic rate of cells was detected with flow cytometry according to the method from Zhang et al. (5) The expression of tyrosine hydroxylase (TH) mRNA in PC12 cells was detected with RT-PCR methods according to the modified method from Peng et al. MAIN OUTCOME MEASURES : Comparison of relative survival rate, apoptosis rate, the expression of IR mRNA and TH mRNA and cell apoptosis. RESULTS: (1) After 12-hour incubation of 100, 200, 300 and 1 000 μmol/L MPP^+, the relative survival rate of PC12 cells was (72.88±2.91)%, (60.64±0.81)%, (54.56±0.76)% and (16.89±2.83)%, respectively, which was significantly lower than that of blank control group (100%, P 〈 0.05); After 12, 18 and 24-hour incubation, the relative survival rate of PC12 cells was (54.56±0.76)%, (42.43±0.16)% and (23.56±0.17)% respectively, which was significantly lower than that of blank control group (100%, P〈 0.05); When 15, 50 and 100 nmol/L insulin was pre-added to cells, the relative survival rate was (70.10±0.16)%, (78.01 ±2.43)% and (83.55±1.43)%, respectively, which was significantly higher than MPP^+ alone [(54.56±0.76)%, P 〈 0.05]. (2) Appototic bodies were rarely seen in the blank control group, but densely gathered in the MPP^+ group and were significantly decreased in the insulin group. (3) Apoptosis rate of PC12 cells in the MPP^+ group was significantly higher than that in the blank control group [(36.56±0.89)% vs. (2.34±0.23)%, P〈 0.05], and that in the 15, 50, 100 nmol/L insulin group [(30.01±0.04)%, (24.23±0.37)%, (20.01 ±1.01)%, respectivelyl was significantly lower than that in MPP^+ group (P 〈 0.05). (4) The TH mRNA expression in PC12 cells in MPP^+ group was significantly lower than that in blank control group; The expression of TH mRNA in insulin group was gradually increased in an insulin dose-dependent manner. There were no significant changes in the expression of IR mRNA under different experimental conditions. CONCLUSION: Insulin can resist MPP^+-induced apoptosis of PC12 cells, lessen the damage of PC12 cells, but does not change the gene expression of target cell insulin receptor.
文摘Objective: To explore the protective effect of minocycline on the apoptosis of cellular parkinsonism models induced by MPP^+ . Methods: Using PC12 cells as the apoptotic model of dopaminergic neurons, MC and MPP^+ were added into the culture medium of PC12 cells, and using MTr to assay the cell viability and metabolic state; The cells apoptosis was assayed by electrophoresis method and using flow cytometry FACS to assay the apoptosis ratio. Results: Added the MPP^+ to get the concentration of 10μmol/L, the cellular parkinsonism model of apoptosis had been prepared. The pre-treatment of MC ( 100/μmol/L) could significantly increase the PC12 cell viability. The apoptosis ratio of MC+MPP^+ group was significantly lower than that of MPP^+ group, but was still significantly higher than that of control group. Conclusion: MC may protect the cell apoptosis induced by MPP^+ to some extent.
基金the Major Projects of National Science and Technology, No.2009ZX09103-329the National Natural Science Foundation for Distinguished Young Scholars of China, No.30901974+1 种基金Outstanding Youth Science Fund Program of Heilongjiang Province, No.JC200705"Spring Sunshine" Plan of Ministry of Education, No.2006
文摘Apoptosis and viability of PC12 cells following 1-methyl-4-phenylpyridinium ion (MPP+)-induced injury were monitored by flow cytometry, following Annexin V-propidium iodide double labeling, and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, respectively. The release of lactate dehydrogenase, superoxide dismutase activity and levels of malondialdehyde were determined by UV spectrophotometry. The changes in mitochondrial membrane potential and the intracellular concentration of calcium were determined by flow cytometry, and the activity of caspase-3 was monitored by western blot. According to cell viability and apoptosis studies, MPP+-induced apoptosis in PC12 cells was inhibited in the presence of 10 tJg/mL of Eleutheroside B Our results indicate that the neuroprotective effect of Eleutheroside B, following MPP+-induced apoptosis in PC12 cells, involves increasing the anti-oxidative stress capacity of cells, maintaining the high-energy state of mitochondrial membrane potential, reducing intracellular calcium concentration and inhibiting caspase-3 activity.
文摘The extraction behavior of rare earths was studied by using paraffin with ceresin as a diluent containing 1-phenyl-3-methyl-4-benzoyl-pyrazolone-5.In solid phase,the composition of complexes is REP_3.The equilib- rium extraction constants and pH_(1/2) values of solid-liquid extraction are higher than those of normal liquid-liquid extraction.The extraction efficiency tends to maximum when the ratio of phases is 1:1.When the extraction temperature is higher than the melting point of paraffin and the extraction time is over 10 min,the extraction efficiency keeps constant.Moreover,the relationship among separation factor,equilibrium extrac- tion constant,pH_(1/2) value and atomic number was obtained.The mechanism of solid-liquid extraction is analogous to that of liquid-liquid extraction.
基金the National Natural Science Foundation of China, No. 30370499
文摘BACKGROUND: To date, a complete protein expression profile of the midbrain substantia nigra in a mouse model of chronic Parkinson's disease, induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), does not exist. In addition, there are no reports of analysis of differential protein expression. OBJECTIVE: To separate and evaluate MPTP-induced differential protein expression through the use of proteomics in the substantia nigra of a mouse model of chronic Parkinson's disease. DESIGN: Randomized controlled animal study. SETTING: Department of Neurology, the First Affiliated Hospital, Chongqing Medical University. MATERIALS: Sixteen 8-10-week old, healthy, male, C57BL mice, weighing 20-25 g, and of clean grade, were provided by the Experimental Animal Center of Chongqing Medical University. The experimental animals were disposed according to ethical criteria. MPTP was provided by Sigma Company, USA; Pdquest 2D image analysis software and gelatum/irradiance image analysis system (ChemiDoc XRS) by Bio-Rad, USA; and Voyager DE-PROMALD1-TOF-MS mass spectroscopy analyzer by AB1 Company, USA. METHODS: This study was performed in Chongqing Neurological Laboratory between November 2006 and July 2007. Mice were randomly divided into model and control groups, with 8 mice in each group. Mice in the model group were received a subcutaneous injection of MPTP (25 mg&g), twice a week, for five successive weeks, to establish a chronic Parkinson's disease model. Mice in the control group received the same volume of a subcutaneous saline injection at the same time points. Mice were sacrificed by anesthesia to rapidly obtain the midbrain for protein separation of the substantia nigra. MAIN OUTCOME MEASURES: (1) 2-ED handbook (Bio-Rad Company) was referenced for two-dimensional electrophoresis, (2) PDQUEST8,0 analytical electrophoresis pattern was adopted to evaluate differential protein expression. (3) Peptide mass finger print map and data were retrieved on http://www.prospector.ucsf.edu to compare differential substantia nigral protein expression in the two groups. RESULTS: Two-dimensional gel electrophoresis of substantia nigra tissue indicated that there were 33 differential protein expressions between the two groups. Three new proteins were evaluated, including α -enolase, which exhibited regulated expression, tumor necrosis factor ligand superfamily member 4, and cyclin-dependent kinase inhibitor 1B. CONCLUSION: There are three proteins that exhibit differential expression in the substantia nigra- α -enolase, tumor necrosis factor ligand superfamily member 4, and cyclin-dependent kinase inhibitor 1B.
基金This work was supported by the National Natural Science Foundation of China (Grant No. 59833120).
文摘Poly(4-methyl-1-pentene) (PMP) hollow fiber membranes were prepared by the melt-spun and cold-stretch(MSCS) method. Scanning electronic microscopy (SEM) was used to characterize the section and surface structures of themembranes with special asymmetric structure. The preliminary results of gas permeation measurements indicated that the resultant hollow fiber membranes have the potential ability for oxygen/nitrogen separation.
基金the Science Research Foundation of Henan Institute of Science and Technology (No. 06036)
文摘The title compound trans-4-[(5-(2,4-dichlorophenoxy)-3-methyl- 1-phenyl-1H-pyrazol-4-yl)methyleneamino]- 1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one 3 (C28H23Cl2N5O2, Mr = 532.41) has been synthesized and its crystal structure was determined by single-crystal X-ray diffraction analysis. It crystallizes in triclinic, space group P1- with a = 8.9438(4), b = 11.6065(5), c = 14.2215(6)A, α = 112.566(1), β = 92.324(2), γ = 102.91(1)°, V= 1315.65(10) A^3, Z = 2, Dc = 1.344 g/cm^3,μ(MoKa) = 0.282 mm^-1, λ = 0.71073 A, F(000) = 552, the final R = 0.0587 and wR = 0.1578 for 5071 observed reflections (I 〉 2σ(I)). X-ray analysis reveals that the product is a thermodynamically stable trans isomer. Intra- and intermolecular C( 12)-H(12)…O(1) and C(28)-H(28)...O(1)# 1 hydrogen bonds were observed in the title compound.
基金supported by the Natural Science Foundation of Hubei Province (2006ABB016)Key Science Research Project of Hubei Provincial Department of Education (No.D200724001) the Science Research Project of Yunyang Medical College (No. 2006QDJ16)
文摘The crystal structure of the title compound ethyl 3-(4-chlorophenyl)-3,4-dihydro-6- methyl-4-oxo-2-(pyrrolidin-1-yl)furo[2,3-d]pyrimidine-5-carboxylate (C20H20ClN3O4, Mr= 401.84) has been prepared and determined by single-crystal X-ray diffraction. The crystal is of monoclinic, space group P21/n with a = 20.6215(9), b = 8.5311(4), c = 21.6886(9) A^°, β = 91.607(1)°, V = 3814.0(3)A^°^3, Z = 8, Dc = 1.400 g/cm^3, F(000) = 1680, μ = 0.233 mm^-1, R = 0.0718 and wR = 0.1545 for 6717 observed reflections with I 〉 2σ(I). X-ray diffraction analysis reveals two crystallographically independent molecules in the asymmetric unit.
基金supported by the National Natural Science Foundation of China,Nos.82271257(to YZ)and 82071228(to YZ)Qing Lan Project(to YZ)+1 种基金Open Competition Grant of Xuzhou Medical University(to YZ)Postgraduate Research&Practice Innovation Program of Jiangsu Province,No.KYCX21_2705(to TS)。
文摘Microglia-mediated neuroinflammation is considered a pathological feature of Parkinson's disease.Triggering receptor expressed on myeloid cell-1(TREM-1)can amplify the inherent immune response,and crucially,regulate inflammation.In this study,we found marked elevation of serum soluble TREM-1 in patients with Parkinson's disease that positively correlated with Parkinson's disease severity and dyskinesia.In a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease,we found that microglial TREM-1 expression also increased in the substantia nigra.Further,TREM-1 knockout alleviated dyskinesia in a mouse model of Parkinson's disease and reduced dopaminergic neuronal injury.Meanwhile,TREM-1 knockout attenuated the neuroinflammatory response,dopaminergic neuronal injury,and neutrophil migration.Next,we established an in vitro 1-methyl-4-phenyl-pyridine-induced BV2 microglia model of Parkinson's disease and treated the cells with the TREM-1 inhibitory peptide LP17.We found that LP17 treatment reduced apoptosis of dopaminergic neurons and neutrophil migration.Moreover,inhibition of neutrophil TREM-1 activation diminished dopaminergic neuronal apoptosis induced by lipopolysaccharide.TREM-1 can activate the downstream CARD9/NF-κB proinflammatory pathway via interaction with SYK.These findings suggest that TREM-1 may play a key role in mediating the damage to dopaminergic neurons in Parkinson's disease by regulating the interaction between microglia and peripheral neutrophils.
文摘Several cyclopropanation catalysts for the synthesis of 3(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylates have been studied in this paper. Owing to electron deficiency of 1,1-dichloro-4-methyl-1,3-pentadiene, yield of this reaction is rather law compared with that of 2,5-dimethyl-2,4-pentadiene, Of all catalysts concerned. yield ranged from 25.1% to 47.2%.
基金supported by the Jiangsu Province College Students’ Practice and Innovation Training Program(No.201810323007Z)
文摘Two new Schiff bases based on 5-chloro-3-methyl-1-phenyl-1 H-pyrazole-4-carbaldehyde, namely, N-((5-chloro-3-methyl-1-phenyl-1 H-pyrazol-4-yl)methylene)-4-morpholinoaniline(Ⅲa) and N-((5-chloro-3-methyl-1-phenyl-1 H-pyrazol-4-yl)methylene)-3-fluoro-4-morpholinoaniline(Ⅲb), were synthesized and characterized by IR, LC-MS, 1 H NMR and 13 C NMR spectroscopy. Meanwhile, the three-dimensional configurations of the two title compounds were further characterized by single-crystal X-ray diffraction analyses. Both the compounds are thermodynamically stable trans-isomers. Moreover, the fluorescence properties and antioxidant activities against DPPH of the two target compounds have been investigated, and the results showed that the title compounds both have fluorescence performance and certain antioxidant activities against DPPH radical.
基金the grants from Shanghai Educational Committee, No. 03BZ03Department of Education for Doctor Foundation, No. 20040266014Shanghai Jiao Tong University Medical School for Doctor Foundation, No. BXJ0304
文摘At present, pathogenesis and mechanism of Parkinson disease (PD) are still unclear. Animal models of PD are essential tools in studies on etiology and therapy and should mimic the chronic pathological process, histological characteristics and motor behavior dysfunction. In recent years, transgenic mice have been widely utilized to study the mechanism of PD, and it has become imperative that a PD mouse model of motor behavioral dysfunction be established. OBJECTIVE: To compare the behavioral and histochemical characters of two neurotoxic mice model induced with 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenyl-1, 2, 3, 6 -tetrahydropyridine (MPTP), and a better method to mimic Parkinson disease will be found out. DESIGN: Parallel experiment. SETTING: Laboratory of Molecular Genetics, Department of Medical Genetics, Shanghai Jiao Tohg University. MATERIALS: Sixty 129Sv/C57BL6J male wild mice, SPF grade, 8 - 12 weeks old, weighing 20 - 25 g, were provided by Experimental Animal Center, Shanghai Jiao Tong University. All the surgery operation was performed according to the rules of Shanghai Jiaotong University Animal Committee. METHODS: The experiment was carried out in the Laboratory of Molecular Genetics (National Key Laboratory), Department of Medical Genetics, Shanghai Jiao Ttong University from March to August 2006. ①Thirty-two male mice were randomly divided into control group and drug treatment group with 16 mice in each group. Surgery was carried out and 6-OHDA was administrated to substantia nigra pars compacta (SNpc) and nigra-striatum pathway according to the different parameters with intoxication apparatus. Saline was injected to the other 16 mice according to the same paradigm. 1 mg/kg apomorphine was injected intraperitoneally 2 weeks later after surgery to induce the imbalanced rotation behavior for 40 minutes. ②Twenty-eight mice were randomly divided into 4 groups with 7 in each group, including low-dose, moderate-dose, high-dose groups and negative control group. Then, mice in the drug treatment group were injected intraperitoneally with 5, 10 and 15 mg/kg MPTP for 9 successive days. In addition, mice in the control group were injected with the same volume of saline for 9 days. Pole test and stride length test were utilized to detect coordinative behavioral dysfunction. Mice were sacrificed 20 days after MPTP treatment, and histochemical staining of tyrosine hydroxynase (TH) was used to observe the loss of dopaminergic neuron in SNpc. MAIN OUTCOME MEASURES: ① Success ratio of each model establishment method; ② inducible asymmetric cycle behavior test 2 weeks after 6-OHDA injection; ③behavioral dysfunction in pole test and stride length, morphological changes in brain tissue. RESULTS: Totally sixty mice were used in this experiment and 3 mice were excluded because of the hypersensitivity or the clumsy reaction in motor behavioral detection before MPTP treatment, therefore, data was analyzed with the rest 57 mice. ① Lethal ratio: Three out of 16 mice died in striatum injection group and 5 out of 16 mice died in nigro-striatal pathway group. No mouse died in MPTP treatment groups. ② Locomotor behavior: No dysfunction of locomotor was found in 6-OHDA treatment groups. However, several motor behavioral dysfunction were start to present at the 4th day of MPTP injection. ③ Asymmetric cycle behavior: No asymmetric cycle was induced successfully two weeks after 6-OHDA surgery. Mice show hypersensitive behavior 10 minutes after apomorphine injection, which lasted for about 20 minutes. ④ Pole test: From the 4^th day of MPTP treatment, mice started to display coordinate dysfunction, such as climbing down along the pole in spiral, moving slowly with hesitation. Some mice could not grab the pole and slide down along the pole at 4th day post injection. Comparing with 0 dose control group, all the threedrug treatment groups show significant different dysfunction from the 4th day to the 20th day post injection (P 〈 0.01). ⑤ stride length test: Mice's stride length decreased, when treated with MPTP, and the mice in the high dose group displayed obviously. ⑥ Dopaminergic neuron stained with TH in nigra pars compacta: The results indicated that administrated MPTP (from low dose to high dose) by intraperitoneal cause chronic lesions on the dopaminergic neuron in the SNpc. CONCLUSION: PD mice models induced with 6-OHDA show high mortality ratio and no asymmetric cycle was found after apomorphine injection. However, injection of MPTP intraperitoneally can simulate the chronic pathway of PD, typical histological changes are found and stable motor behavioral dysfunctions are displayed.
基金the National Nat-ural Science Foundation of Chi-na, No. 30270433 a grant fromTechnological DevelopmentPlanning of Beijing Committeeof Education, No.KM200310025092*
文摘BACKGROUND : To summarize the metabolic pathway of 1-methyl-4-phenyl-1,2,3,6-tetradropyridine (MPTP) and its mechanism in inducing Parkinson disease. DATA SOURCES: A computer-based online search of Medline database was undertaken to identify articles about the metabolic pathway of MPTP and its mechanism in inducing Parkinson disease published in English between January 1996 and August 2004, the keywords were "MPTP, Parkinson disease". Meanwhile, Chinese relevant articles published between January 2000 and August 2004 were searched in Wanfang database with the keywords of "MPTP, Parkinson disease". STUDY SELECTION: More than 300 relevant literatures were retrieved, and the full-texts were further searched, those about the establishment of animal models, molecular mechanism of MPTP neurotoxicity and the metabolism were selected, and the obviously repetitive ones, case report and reviews were excluded, finally 18 of them were selected for summarization. DATA EXTRACTION: The 18 literatures were categorized according to MPTP induced animal models of Parkinson disease, mechanism of MPTP in inducing apoptosis in models of Parkinson disease, role of dopamine in the neurotoxic mechanism of MPTP, the role of reactive oxygen species and nitric oxide in the neurotoxicity of MPTP. DATA SYNTHESIS: Animal models of Parkinson disease induced by MPTP can not only produce the clinical characters of Parkinson disease, also duplicate the main biochemical and pathological changes of Parkinson disease. The metabolic pathway of MPTP and its mechanism in inducing Parkinson disease included producing free oxygen and nitric oxide, damaging mitochondrial respiratory chain, and inducing apoptosis, etc. which could all lead to the degeneration and loss of dopaminergic neurons. CONCLUSION : Although some aspects of the models of Parkinson disease are different from that in human beings, we can still know the neurodegeneration of Parkinson disease through studying the molecular mechanism of MPTP.