Objective:To identify the effect of ?-synuclein overexpression on mitochondrial membrane structure with atomic force microscopy. Methods:?-syn expression was mediated by AAV (adeno-associated viral vector) and Recombinant AAV/?-syn and AAV/LacZ viral particles were stereotaxically injected in the left side of rat substantia nigra (SN) for rat model of ?-synuclein overexpression. Mitochondria were isolated from rats SN of Brain. Mitochondria were analysis with JC-1 staining,atomic force microscopy and Western blot. Results:By 16 weeks post-infection of AAV-?-syn,the level of ?-syn increased about 2 times in mitochondrial fraction with Western blot and mitochondrial membrane potential (??) decreased with JC-1 staining. Furthermore,mitochondria swelling and porous like structure formed on the mitochondrial membrane with atomic force microscopy. Conclusion:The data suggested that ?-syn could accumulate in mitochondria,might form mitochondrial membrane pores and lead to ?? decreases. ?-syn might lead to mitochondrial dysfunction in Parkinson's disease.

Mitochondrial dysfunction has been implicated in the aetiology of sporadic Parkinson's disease but its role in the disease mechanism remains unclear.To investigate the effect of synuclein on mitochondrial dysfunction induced by rotenone.The human dopaminergic SH-SY5Y cells were used as a cell model.The cells over-expressed the wild-type ?-synuclein were treated with complex I inhibitor rotenone.The cell viability,complex I activity,Mitochondrial swelling and O2-content were tested at different time point-1w,2w,4w after rotenone treated.CCK-8 test results showed that the cell viability of overexpressed ?-synuclein(SH-SY5Y-Syn)was much lower than the control group(SH-SY5Y-Ctr).After administrating with rotenone about 1w or 2w the cell viability of SH-SY5Y-Syn became higher than that of SH-SY5Y-Ctr.On the 4th week the results were contrary to the first 2 weeks.Similar results were got when test the mitochondrial function.In the first 2 weeks after roteoone administrating,the mitochondrial function of SH-SY5Y-Syn was better than that of SH-SY5Y-Ctr.This suggest that the ?-synuclein could protect the mitochondrial against the injury induced by rotenone in the early stage-1w,2w,while this effect disappeared in the final stage-4w.

According to the characteristics of the etiology and pathogenesis of child cerebral palsy, on the basis of "regulating the mind in treatment of all kinds of diseases" and "regulating the functions of five zang organs with back-shu points", Professor DONG Gui-rong applied the penetrating needling technique on the scalp points and acupuncture at back-shu points of five zang organs in the treatment of child cerebral palsy. The valuable clinical experiences have been summarized as "regulating the mind with scalp needling technique, benefiting the brain and opening the orifice", "regulating five zang organs with back-shu points" and "integration of acupuncture and rehabilitation, and function reconstruction". Two effective cases were introduced.
Acupuncture Points ; Acupuncture Therapy ; Cerebral Palsy ; therapy ; Child, Preschool ; Humans ; Male ; Treatment Outcome

Taxus canadensis distributed mainly in North America, such as northern Minnesota, Newfoundland, south to Wisconsin and Pennsylvania. Its composition has been shown to be very different from other species, and in recent years, some new skeletons also have been found in Canada yew. Through analysis of the taxanes content on various Taxus plants containing taxanes, the results showed a higher content of taxol in T. canadensis. Based on the current research on T. canadensis (from the research results of the author in recent years, as well as from studies of scholars in the field), the paper outlined the research progress in recent years on the chemical constituents of taxane of T. canadensis and the spectral characteristics of various types of compounds. Besides, this paper analyzed the present research about solutions for the taxol drug source crisis.
Animals ; Bridged-Ring Compounds ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Molecular Structure ; Plant Extracts ; chemical synthesis ; chemistry ; pharmacology ; Plants, Medicinal ; chemistry ; Taxoids ; chemical synthesis ; chemistry ; pharmacology ; Taxus ; chemistry

A novel citrinin derivative, penicitrinol L (1), along with two known analogues, penidicitrinin B (2) and pennicitrinone A (3) were isolated from the marine-source fungus Penicillium citrinum. The structure of the new compound was elucidated by spectroscopic methods including one and two-dimensional NMR as well as high-resolution mass spectrometric analysis. Furthermore, compound 1 showed modest cytotoxic activity against HL-60 cell line and compound 3 showed weak cytotoxic activity against A375 cell line.
Antineoplastic Agents ; chemistry ; isolation & purification ; Citrinin ; analogs & derivatives ; chemistry ; isolation & purification ; HL-60 Cells ; Humans ; Magnetic Resonance Spectroscopy ; Penicillium ; chemistry

Objective To assess the influencing factors of the progression of carotid atherosclerotic stenosis using color Doppler flow imaging (CDFI). Methods From January 2009 to December 2014, a total of data 279 consecutive patients first assessed by CDFI as moderate stenosis of carotid atherosclerosis (stenosis rate 50 -69%)and regularly reexamined with CDFI at 12,24 and 36 months after initial examination were enrolled retrospectively. The residual diameter of vascular lesions and the changes of hemodynamic parameters were documented,and they were divided into either a progression group (n = 40)or a non-progression group (n = 239,and the non-progression group was divided into steady group[n = 210]and improved group [n = 29])according to whether the degree of stenosis progressed into severe stenosis (stenosis rate 70 -99%)or occlusion. The effects of the risk factors for common cerebrovascular disease and taking lipid lowering drugs (atorvastatin 20 mg/ d)on stenosis progression were compared in patients between the 2 groups. There were significant differences in hypertension,smoking and the regular use of atorvastatin . The effects of those factors on the progression of carotid stenosis were compared further through Logistic regression analysis. Results The residual vascular diameters of stenosis at 24,and 36 months were reduced obviously in the progression group compared with those of the non-progression group. There was significant difference (all P < 0. 05),and both the stenotic sites and distal peak systolic flow velocity ratio were significantly higher than those of the steady group and improved group (all P < 0. 05). Among the risk factors for cerebrovascular disease,hypertension (OR,2. 686,95% CI 1. 120 -6. 442,P = 0. 027)and smoking (OR,2. 265,95% CI 1. 081 -4. 746,P = 0. 030)were the major risk factors for affecting the progression of carotid stenosis. Regularly taking atorvastatin was a protective factor of delaying the progression of carotid stenosis (OR,0. 383,95% CI 0. 178 -0. 827,P = 0. 015). Conclusions CDFI may objectively evaluate the progression of carotid stenosis. Smoking and hypertension are the independent risk factors for affecting the progression of carotid stenosis,and regularly taking atorvastatin contributes to delay the progression of carotid stenosis.

Objective To investigate the useful parameters of transthoracic echocardiography (TTE) for the diagnosis of stroke subtypes in patients with acute cerebral infarction.Methods One hundred and one acute ischemic stroke patients met all of the following criteria including ≥50 years of age,normal sinus rhythm on admission,and transesophageal echocardiography (TEE) within 7 days from the onset.The clinical significance of the TEE parameters on admission was examined for identifying intracardiac thrombus formation as follows; left atrial dimension,left ventricular end-diastolic dimension,percentage fractional shortening,left ventricular mass index,ratio of the transmitral inflow velocities (E/A),and the deceleration time of the E wave.Results There were 28 patients with E/A ≥ 1.0 (70 ± 12) years old and 73 with E/A ＜ 1.0 (73 ± 10) years old.No patients showed pulmonary congestion on chest radiography.There were no significant differences in age,TTE parameters,and plasma levels of brain natriuretic peptide between the two groups.Patients with E/A≥ 1.0 had higher incidence of left atrial appendage (LAA)thrombus formation and/or spontaneous echograhic contrast than those with ＜ 1.0 (25.0％ vs 5.5％,x2 =7.95,P ＜0.01).A significant relationship was found between E/A and emptying flow velocity of the LAA (r =-0.569,P ＜0.01).Multivariate logistic regression analysis showed E/A was an independent predictor for LAA thrombus (risk ratio 1.531 per0.1 increase,95％ confidence interval 1.129-2.076,P =0.0002).Conclusions Increased level of E/A on admission was associated with the occurrence of left atrial appendage thrombus formation in patients with acute ischemic stroke.

Objective: To identify the functional domain of ?-Synuclein in affecting mitochondrial function and how the function to be impaired,especially,the mitochondrial membrane potential and the release of Cytochrome c.Methods: Harvest of ?-Syn-N and ?-Syn-△N by PCR,then subcloned into the pCMV-Myc mammalian expression vector.The recombinant plasmids were transfected into HEK293T cells by Lipofectamine 2000.After detecting the protein expression by Western blot,the functional domain was detected by co-immunoprecipitation.The mitochondrial membrane potential through flow cytometry and immunofluorescence,at the same time,the release of Cytochrome c through flow cytometry to detect.Results: The recombinant plasmids were constructed successfully.CO-IP has proved that N-terminal may be the functional domain of ?-Synuclein in affecting mitochondria.Over-expression of N-terminal could depolarize the mitochondrial membrane potential and induce the Cytochrome c releasing in MN9D cells.Conclusion: N-terminal may be the functional domain of ?-synuclein and over-expression of N-terminal could decrease mitochondrial activity.

Animals ; CHO Cells ; Cricetulus ; Doxycycline ; pharmacology ; Immunohistochemistry ; Ki-67 Antigen ; genetics ; metabolism ; Plasmids ; Quality Control ; Staining and Labeling ; methods ; Transfection

Alcoholism ; metabolism ; Animals ; Cyclin-Dependent Kinase 5 ; metabolism ; Glucosides ; pharmacology ; Male ; Prefrontal Cortex ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Stilbenes ; pharmacology