Objective To explore the effects of beraprost sodium (BPS) on angiotensin Ⅱ(AngⅡ)-induced podocyte apoptosis and the relationship between BPS and peroxisome proliferator activated receptor δ(PPARδ). Methods Differentiated mouse podocytes were exposed to AngⅡ, further treated with BPS (or GSK0660) for 24 h. Podocyte apoptosis was detected by flow cytometry and AnnexinV-FITC staining. Bax , Bcl-2 and PPARδ mRNA were assessed by RT-PCR. Results AngⅡ promoted podocyte apoptosis and Bax mRNA expression significantly, down-regulated Bcl-2 and inhibited PPARδ mRNA (P < 0.05). Conversely, treatment with BPS reduced AngⅡ-induced podocyte apoptosis and Bax mRNA expression and promoted Bcl-s expression significantly resulting in an increase of PPARδ mRNA expression (P < 0.05). With the inhibition of PPARδ, podocyte apoptosis and Bax mRNA expression increased while Bcl-2 mRNA expression reduced. Conclusion BPS can effectively reduce AngⅡ-induced podocyte apoptosis , which is associated with the activation of PPARδand regulation of Bcl-2/Bax mRNA expression.

Objective To investigate the status of self-care ability and cognition among disabled elderly,and to analyze the relationship between self-care ability and cognition,then analyze their influencing factors.Methods A total of 813 disabled elderly accepted long-term care at community or facility were recruited by stratified sampling method and investigated by socio-demographic questionnaire,activities of daily living and short portable mental status questionnaire.Results The total scores of self-care ability of the long-term care disabled was 32.01±11.59,and the total points of cognition was 3.77±3.24.Disabled elderly with severe disorders of self-care ability had a higher obstacle rate in every cognition ability than those with mild disabilities (P＜0.001).There were differences in orientation and memory function with different persistent disabled time (x2 =11.875,14.758,P＜0.01).Disabled elderly with cognition obstacles have a higher obstacle rate in every self-care aspect than those with normal cognition (P＜0.01).The multiple regression analysis showed that the educational level (β=-0.067),arital status (β=-0.071),disabled persistence time (β=0.121),orientation ability (β=0.403),the amount of cognition obstacles (β=0.443) were the influence factors of Basic Activities of Daily Living(BADL) among disabled elderly ; and disabled persistence time (β=0.116),orientation ability (β=0.417),recalled ability (β=0.275),memorial ability (β=0.189),calculative ability (β=0.257),the amount of cognition obstacles (β=0.358) were the important factors influence Instrumental Activities of Daily Living(IADL).Conclusion The self-care ability and cognition of the long-term care elderly were declining sharply,and influencing each other.It is advisable to offer them direct long-term care service combined with the laws and characteristics of cognition and self-care ability.

Objective To investigate flow patterns at carotid bifurcation in vivo by combining computational fluid dynamics(CFD)and MR angiography imaging.Methods Seven subjects underwent contrast-enhanced MR angiography of carotid artery in Siemens 3.0 T MR.Flow patterns of the carotid artery bifurcation were calculated and visualized by combining MR vascular imaging post-processing and CFD. Results The flow patterns of the carotid bifurcations in 7 subjects were varied with different phases of a cardiac cycle.The turbulent flow and back flow occurred at bifurcation and proximal of internal carotid artery (ICA)and external carotid artery(ECA),their occurrence and conformation were varied with different phase of a cardiac cycle.The turbulent flow and back flow faded out quickly when the blood flow to the distal of ICA and ECA.Conclusion CFD combined with MR angiography can be utilized to visualize the cyclical change of flow patterns of carotid bifurcation with different phases of a cardiac cycle.

Objective To explore the methods and clinical value of transrectal ultrasound (TRUS) in detecting rectal gastrointestinal stromal tumor(GIST) with head scanning probe.Methods A total of 12 patients had the ultrasonic examination through the rectum with the head scanning probe.Preoperative ultrasonic findings were compared with the pathological results.Results Of the 12 patients,the patients were divided into three groups,including 3 cases with low-degree severity,6 cases with moderate-degree severity and 6 cases with high-degree severity.The lymph node metastasis was not found near intestines.Rectal GIST appeared as a hypoechoic mass with clear limit、regular form and expanded growth under TRUS.The CDFI showed abundant flow in the tumor and TRUS had an overall accuracy rate of 75.0%(9/12)in the diagnosis of rectal GIST.The accuracy of TRUS in the staging diagnosis of rectal GIST was 83.3%(10/12).Conclusion The TRUS with the head scanning probe is of great value for pre-operative diagnosis and staging of rectal GIST.Rectal water window and felicitous check-up technique can enhance the accuracy of TRUS.

OBJECTIVETo investigate the effects of the quinoline derivative PQ1 combined with cisplatin on the proliferation and gap junction communication of prostate cancer PC3 cells.

METHODSWe cultured in vitro prostate cancer PC3 cells and divided them into DMSO blank control, cisplatin control, and cisplatin (10 mg/ml) plus PQ1 (1, 2, 5, 10, and 15 μmol/L) groups. We measured the proliferation of the prostate cancer PC3 cells, determined the expressions of the connexin 43 (Cx43) mRNA and protein by RT-PCR and Western blot, and compared the indexes among different groups.

RESULTSCisplatin combined with PQl at 1 - 10 μmol/L significantly inhibited the proliferation of the PC3 cells and the inhibition rate rose in a concentration- and time-dependent manner, from (48.72 ± 0.98)% vs (50.33 ± 0.62)% at 0 μmol/L to (77.38 ± 1.12)% vs (83.50 ± 1.05)% at 15 μmol/L at 24 and 48 hours (P < 0.05). Compared with the cisplatin control, cisplatin combined with PQ1 at 1, 2, 5, 10, and 15 μmol/L increased the expression of Cx43 mRNA from 0.379 ± 0.113 to 0.669 ± 0.031, 0.831 ± 0. 127, 0.769 ± 0.100, 0.532 ± 0.086, and 0.475 ± 0.134, respectively (P < 0.05), and cisplatin combined with PQ1 at 1, 2, 5, and 10 μmol/L elevated that of Cx43 protein from 0.138 ± 0.146 to 0.263 ± 0.111, 0.306 ± 0.152, 0.415 ± 0.280, and 0.643 ± 0.310, respectively (P < 0.05).

CONCLUSIONThe quinoline derivative PQ1 can promote the gap junction communication of prostate cancer PC3 cells and enhance the killing effect of cisplatin on PC3 cells by upregulating the expressions of Cx43 mRNA and protein.

Aminoquinolines ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cisplatin ; pharmacology ; Connexin 43 ; genetics ; metabolism ; Dose-Response Relationship, Drug ; Gap Junctions ; drug effects ; physiology ; Humans ; Male ; Prostatic Neoplasms ; metabolism ; pathology ; physiopathology ; RNA, Messenger ; metabolism ; Time Factors

PEG-modified magnetic Fe3O4 (Fe3O4-PEG) nanoparticles were sythesized using a solvothermal reaction and characterized with transmission electron microscopy (TEM) and thermo gravimetric analysis (TGA). The photothermal effect and photothermal destruction of cancer cells were evaluated. Then the doxorubicin loaded Fe3O4-PEG (DOX-Fe3O4-PEG) nanoparticles were prepared. The cytotoxicity and combined chemotherapy/photothermal therapy (PTT) effect were investigated. Uniform PEG coated Fe3O4 nanoparticles with particle size of 155 nm were obtained in the experiment. The loading and release of doxorubicin on Fe3O4-PEG were pH-dependent. The drug loading capacity in water was 21%. The results of MTT indicated a good biocompatiblity of Fe3O4-PEG nanoparticles and high cytotoxicity of DOX-Fe3O4-PEG. In combined therapy experiment, photothermal therapy demonstrated unambiguously enhanced chemotherapy efficacy. In conclusion, the obtained Fe3O4-PEG nanoparticles which exhibit good photothermal effect and drug loading capacity can be used for chemotherapy and photothermal therapy. The synergetic anti-tumor activity indicates the potential for the combined application of chemotherapy and photothermal therapy in cancer treatment.
Antibiotics, Antineoplastic ; administration & dosage ; pharmacology ; Cell Survival ; drug effects ; Doxorubicin ; administration & dosage ; pharmacology ; Drug Carriers ; Ferrosoferric Oxide ; chemistry ; Humans ; Hyperthermia, Induced ; MCF-7 Cells ; Magnetite Nanoparticles ; chemistry ; Particle Size ; Polyethylene Glycols ; chemistry

Objective HupA is one of the potential drugs which can be used to treat Alzheimer's disease(AD).The aim of this study was to explore the pharmacokinetics and biodistribution of HupA in vivo by using 11C-HupA.Methods A total of 25 SD rats were studied.They were divided into 5 groups (5 rats in each group).All had intravenous injection of 22 MBq(in0.2 ml)11C-HupA through tail vein.Dynamic im-aging Was acquired from 5 to 90 minutes after injection.Venous blood and organ activities were collected at 5,15,30,60.and 90 minutes after injection.Percentage activity of injected dose per gram of tissue(%ID/g)was calculated to characterize the biodistribution of tracer in different brain regions: frontal,apical, temporal,occipital,cerebellum,hippocampus,striatum,thalamencephalon, and brain stem, Variance analysis using SPSS 11.5 software was performed and compared among the study groups.Results 11C-HupA was character-istic for its quick clearance from blood,with half time T1/2 of (14.61±1.77) min,and clearance rate (CL)macokinetics of 11C-HupA in rats corresponded to a one-compartment model.with an activity curve(area 11C-HupA distribution in different brain regions,being greater in cerebral cortex,hippocampus,hypothala-mus and brain stem. Conclusions Pharmacokinetic study of 11C-HupA in brain was fast.convenient and showed high specificity and sensitivity.Its ability to quantitatively evaluate brain function and its character-istic distribution in mice provided some evidence for monitoring therapy in AD patients.

The technique of liquisolid compress is a new technique developed in 1990s, which was considered to be the most promising technique to improve the dissolution of water-insoluble drugs. In this article, tanshinone II(A) and the extracts of the ester-solubility fractions were chosen as the model drugs to evaluate the effects of the liquisolid technique for enhancement of dissolution properties of tanshinone II(A). Several liquisolid tablets (LS) formulations containing different dosage of drugs and various liquid vehicle were pre-pared and for all the formulations, microcrystalline cellulose and silica were chosen as the carrier and coating materials to evaluate their flow properties, such as angle of repose, Carr's compressibility index and Hausner's ratio. The interaction between drug and excipients in prepared LS compacts were studied by differential scanning calorimetry(DSC) and X-ray powder diffraction (XRPD). The dissolution curves of tanshinone II(A) from liquisolid compacts were investigated to determine the technique's effect in improving the dissolution of tanshinone II(A) and its impacting factors. According to the results, the dissolution increased with the rise in the dissolution of the liquid-phase solvent. The R-value and drug dosage can significantly affect the drug release, but with less impact on active fractions. This indicated that liquisolid technique is a promising alternative for improvement of dissolution property of water-soluble drugs, and can make a synergistic effect with other ester-soluble constituents and bettern improve the release of tanshinone II(A). Therefore, the technique of liquisolid compress will have a better development prospect in traditional Chinese medicines.
Calorimetry, Differential Scanning ; Diterpenes, Abietane ; chemistry ; Solubility ; X-Ray Diffraction

Applications of network pharmacology are increasingly widespread and methods abound in the field of drug development and pharmacological research. In this study, we choose rosiglitazone compound as the object to predict the targets and to discuss the mechanism based on three kinds of prediction methods of network pharmacology. Comparison of the prediction result has identified that the three kinds of prediction methods had their own characteristics: targets and pathways predicted were not in accordance with each other. However, the calcium signaling pathway could be predicted in the three kinds of methods, which associated with diabetes and cognitive impairment caused by diabetes by bioinformatics analysis. The above conclusion indicates that the calcium signaling pathway is important in signal pathway regulation of rosiglitazone compound, which provides a clue to further explain the mechanism of the compound and also provides a reference for the selection and application of methods of network pharmacology in the actual research.
Calcium Signaling ; Cognitive Dysfunction ; Computational Biology ; Diabetes Mellitus ; Humans ; Pharmacology ; methods ; Thiazolidinediones ; pharmacology

Objective To compare the protective effect of different dose of penehyclidine hydrochloride (PHC) in rats with myocardial ischemia/reperfusion (I/R) injury.Methods Forty-eight healthy male Wistar rats were randomly divided into six groups (n =8 each):sham group,sham + 1.0 mg/kg PHC group (sham + H-PHC group),I/R group,I/R + 0.1 mg/kg PHC preconditioning group (I/R + L-PHC group),I/R + 0.3 mg/kg PHC preconditioning group (I/R + M-PHC group),and I/R + 1.0 mg/kg PHC preconditioning group (I/R + H-PHC group).I/R injury model was reproduced by ligation followed by release of the coronary artery,and PHC in different dosages was given at 30 minutes before model reproduction.At 3 hours after reperfusion,the left ventricular end-diastolic pressure (LVEDP),left ventricular end-systolic pressure (LVESP),ejection fraction (EF),and fractional shortening (FS) were recorded.The levels of aspertate aminotransferase (AST),MB isoenzyme of creatine kinase (CK-MB),and lactate dehydrogenase (LDH) were determined.The myocardial tissues were harvested for the determination of the area at risk (AAR) and the infarct area (AI),and the percentage of AI/AAR was calculated.The examination of myocardial fiber was performed with electron microscopy.Results Compared with sham and sham + H-PHC groups,LVEDP was increased in I/R groups,LVESP,EF and FS were decreased,and the levels of AST,CK-MB and LDH,as well as the AI/AAR were increased.Compared with I/R group,in pretreatment groups with different doses of PHC,LVEDP was decreased,LVESP,EF and FS were increased,the levels of AST,CK-MB,LDH,and AI/AAR were also decreased,especially in I/R+M-PHC and I/R+H-PHC groups [LVEDP (mmHg,I mmHg =0.133 kPa):11.33± 1.17,9.85± 1.09 vs.15.82 ± 1.79,LVESP (mmHg):98.9 ± 10.6,112.8 ± 10.0 vs.87.8 ± 9.2,EF:0.681 ± 0.074,0.741 ± 0.070 vs.0.569 ± 0.072,FS:(42.4 ± 4.6)％,(46.0 ± 5.1)％ vs.(36.8 ± 3.9)％,AST (U/L):386.97 ± 80.65,298.31 ± 54.88 vs.603.47 ± 173.66,CK-MB (U/L):3.12 ± 0.84,2.88 ± 0.72 vs.7.14 ± 1.54,LDH (U/L):1 784.23 ± 488.49,1 629.37 ± 436.34 vs.2 489.14 ± 460.80,AI/AAR:0.284 ± 0.014,0.223 ± 0.008 vs.0.377 ± 0.011,all P ＜ 0.05].There was significant difference in LVEDP,LVESP,and AI/AAR between I/R + M-PHC group and I/R + H-PHC group (all P ＜ 0.05),and no significant difference in other parameters (all P ＞ 0.05).It was showed by electron microscopic examination that after I/R injury,the myocyte mitochondria membranes were broken,mitochondria were markedly swollen,mitochondrial cristae disappeared;however in I/R+M-PHC and I/R+H-PHC groups,mitochondrial swelling was mild,the capsule was more or less intact,mitochondrial cristae were partly visible,the structure was complete,especially in the group I/R+H-PHC,and the mitochondrial structure was close to normal.Conclusions PHC could protect myocardial from I/R injury.Mid dose of PHC (0.3 mg/kg) and high dose of PHC (1.0 mg/kg) could provide better protective effect than low dose of PHC (0.1 mg/kg),and high dose of PHC is better in effect than the middle dose.