Objective To detect the effects of exenatide on the related indicators of proliferation, invasion and apoptosis of cell line SCC-25. Methods SCC-25 cells were cultured in vitro. The expression level of glucagon like peptide 1 receptor (GLP-1R) was determined by Western blot assay in SCC-25 cells. SCC-25 cells were divided into four groups:control group and exenatide group (1,10 and 100 nmol/L). The ability of cell proliferation was detected using MTT assay after 24 h, 48 h and 72 h of culture. The ability of invasion was measured with Transwell assays. The expression levels of MMP-2, Caspase-3 and Phospho-p38 MAPK were measured by Western blot assay. Results GLP-1 receptor expression was found in SCC-25 cells. Compared with control group, the cell survival rate, invasion rate and the expression of MMP-2 were significantly decreased in SCC-25 group (P＜0.05). The expression of Caspase-3 were significantly increased (P＜0.05).Changes were in a concentration-dependent and time-dependent manner (P＜0.05). The expression of Phospho-p38 MAPK was significantly increased at 24 h in 10 nmol/L exenatide group (P＜0.05). Conclusion Exenatide can inhibit the cell proliferation and invasion, which may contribute the apoptosis by promoting expressions of Phospho-p38 MAPK and Caspase-3 of SCC-25 cells.

BACKGROUND:Bone tissue transplantation or osteogenic material fil ing is after used for bone defect repair. To remove autologous bone tissues can lead to additional damage and secondary deformity, therefore, it is extremely urgent to search for a new osteogenic material. OBJECTIVE:To construct the porousβ-tricalcium phosphate (β-TCP)/col agen scaffold modified with human bone morphogenetic protein 2 (hBMP2) gene, and to observe its effects on differentiation of MC3T3-E1 cel lines. METHODS:The porousβ-TCP/col agen scaffold modified with hBMP2 gene was prepared. Then in vitro culture system of MC3T3-E1 cel lines with composite scaffold was established. There were scaffold and plate groups, and each group was divided into two subgroups according to the different concentrations of plasmid. Samples were col ected and observed morphological y by scanning electron microscope and light microscope after complex culture. After 1, 3, 7 and 14 days of induction, calcium nodules were observed through alizarin red staining, the cel cycle was detected by real-time PCR, and expressions ofαI-chain col agen type I gene, Osterix and bone sialoprotein were observed. RESULTS AND CONCLUSION:The number of cel s adhered, differentated and distributed on the composite scaffold was significantly higher than that of the single scaffold (P<0.05). Alizarin red staining and real-time PCR detection showed that the osteogenesis ability of MC3T3-E1 cel lines in the scaffold group was stronger than that in the plate group. To conclude, the porousβ-TCP/col agen scaffold modified with hBMP2 gene is an appropriate candidate for bone defect repair.

Diseases in Twins ; Epilepsy ; complications ; Epiphyses, Slipped ; etiology ; Femur Head ; Humans ; Infant ; Male

OBJECTIVE To study the effect of valproic acid ( VPA) on radiosensitivity to MCF7 breast cancer cells. METHODS MCF7 cells were pretreated with VPA 0.5 and 1 mmol.L-1 for 0, 24, 48 and 72 h respectively, irradiated with 8 Gy lR, and at 6 h post-lR, the γ-H2 AX foci formation in MCF7 cells was tested by immunofluorescence assay. MCF7 cells were pretreated with VPA 0.5 and 1 mmol.L-1 for 72 h, irradiated with 4 Gy lR, and at 48 h post-lR, the cell survival rate was detected by MTT assay. MCF7 cells were pretreated with VPA 0.5 mmol.L-1 for 24 h, and then irradiated according to the amount of cells: 2 Gy (500 and 1000 cells per plate), 4 Gy (2000 and 4000 cells per plate), 6 Gy (8000 and 16000 cells per plate), and the cloning efficiency was calculated. MCF7 cells were pretreated with VPA 0.5 and 1 mmol.L-1 for 0, 24, 48 and 72 h respectively and the cell cycle profile was analyzed via flow cytometry. RESULTS After treatment with VPA alone for 24 h, MCF7 cells showed a significant increase in the amount of γ-H2 AX foci formation ( P < 0. 01). lt was also found that VPA increased lR-induced γ-H2 AX foci formation, which obviously prolonged the pretreatment time of VPA(P<0.01) in a time-dependent manner(r=0.98, P<0.05). VPA 0.5 and 1 mmol.L-1 had the same effect on γ-H2 AX foci formation. Furthermore, VPA was able to cause a significant decrease in lR-induced clonogenic survival but an increase in lR-induced cytotoxicity by MTT assay. Also, VPA alone decreased the plating efficiency of MCF7 cells. However, the cycle profile of MCF7 cells treated with both VPA 0.5 and 1 mmol.L-1 was not changed. CONCLUSION Without affecting the cell cycle profile, both the safe and critical dose of VPA used in clinical epilepsy treatment can significantly increase the accumulation of DNA double strand breaks in the cells and sensitize the cells to lR treatment, suggesting that VPA can induce radio-sensitization of breast cancer cells.

ObjectiveTo evaluate the quantitative and qualitative changes of peripheral-type benzodiazepine recepors (PBRs) in brain mitochodria and in platelet membrane in aging rats. MethodsMale Sprague-Dawley rats were divided into 3- and 24-month groups. All animals were sacrificed by decapitation and the brains were immediately removed. Mitochondrial components from dissected cerebral cortex were isolated. The membrane of platelets from venous blood was prepared by the method of hypotonic hemolysis. The specific binding assay of the radioactive PBRs antagonist ［3H］PK11195 to membrane was performed. Scatchard analysis was performed to estimate the equilibrium dissociation constant (Kd) and the maximal binding site density (Bmax). ResultsA significant increase in ［3H］PK11195 binding activity in the mitochodria from cerebral cortex in 24-month rats was observed compared to that in 3-month rats(P<0-001). Meanwhile, the Scatchard analysis revealed that there was an increase in Bmax, with a significant increase in Kd in 24-month rats. The same change of ［3H］PK11195 binding activity was noted for platelet membrane in 24-month rats(P<0-001).ConclusionThe density of PBRs increases in cortex mitochondria in aging rats, but the binding affinity of PBRs decreases which may be attributable to the progressive pathogenesis of aging in rats. ［3H］ PK11195 binding activity of platelet membrane might reflect the change of PBRs in the brain tissue.

ABSTRACT:Objective To explore the changes of serum cytokine interleukin-17 (IL-17)in patients with chronic hepatitis B of different clinical types and its clinical significance.Methods We selected 30 cases of mild chronic hepatitis B,34 cases of moderate one,29 cases of severe one,38 cases of liver cirrhosis,and 21 cases of acute on chronic liver failure.Another 30 cases over the same period served as the healthy control group.Cytokine IL-1 7 level in peripheral blood was detected in each group,and all the groups except the control group were detected for liver function and HBV-DNA.These related serum markers were detected and the results were statistically analyzed.Results ① IL-17 in the peripheral blood was (8.103±2.061)ng/mL in healthy control group;(25.551 ±7.078)ng/mL,(45.442±18.358)ng/mL and (75.378±19.05)ng/mL in the groups with mild,moderate and severe chronic hepatitis B;and (97.16±17.066)ng/mL in acute on chronic liver failure group.Its levels gradually increased with the severity;and there were significantly different among the five groups and between every two groups (P<0.01).The peripheral blood level of IL-17 was (8.103±2.061)ng/mL in the healthy control group, (34.517±8.905)ng/mL in compensatory cirrhosis group,and (45.615±15.623)ng/mL in the decompensated cirrhosis group.These three groups had pairwise comparison,and the difference between every two groups was significant (P<0 .0 1 ).The peripheral blood level of IL-1 7 in the decompensated cirrhosis group increased compared with that in the compensatory group.③ In the 1 5 2 cases detected,serum IL-1 7 level and serum ALT,AST,TBIL,HBV-DNA levels were positively correlated,and serum PTA had negative correlation with the level of IL-1 7 .④ In the 2 1 cases of acute on chronic liver failure,the peripheral blood level of IL-1 7 did not significantly differ between antigen-e positive and negative groups (P=0.654).⑤ In 21 patients with chronic on acute liver failure,the level of IL-1 7 in peripheral serum and MELD scores showed a positive correlation by Pearson correlation analysis (r=0.533,P=0.013).Conclusion In patients with chronic hepatitis B,the level of IL-17 in peripheral serum increased with disease severity.Moreover,the level of IL-1 7 in peripheral blood may play a role in promoting the progression of cirrhosis and the development of acute on chronic liver failure.

Objective To investigate the prompt value of abnormal vaginal morphology on diagnosing pelvic organ prolapse . Methods Forty eight pelvic organ prolapse female patients diagnosed by pelvic organ prolapse quantification were enrolled in the pelvic organ prolapse group and 51 normal female volunteers were enrolled in the control group in this study. Pelvic MRI T2WI were performed in all cases. The vaginal shape were evaluated according to Delancey Ⅱ level on the transverse images, which were divided into two categories:normal morphology (H-shaped) and abnormal morphology(non H-shaped). The vaginal shape distribution of different prolapse degree(0,Ⅰ,Ⅱ,Ⅲ,Ⅳstage) and types(anterior,middle, posterior pelvic prolapse) were recorded. Chi-square test was used to analyse distribution difference of vaginal shape between the two groups. The ROC curve was used to analyse the diagnostic efficiency of abnormal vaginal morphology for diagnosing pelvic organ prolapse. Results In the control group, there were 40 cases with normal vaginal morphology and 11 cases with abnormal morphology mainly including W-shaped and U-shaped abnormal morphology. In the prolapse group, there were 5 cases with normal vaginal morphology and 43 cases with abnormal morphologymainly including U-shaped (13 cases), W-shaped (26 cases) and O-shaped(4 cases) abnormal morphology. There was significant difference between the two groups(c2=46.137,P<0.01). The area under the curve (AUC) was 0.800. The sensitivity and specificity of abnormal vaginal shape for diagnosing pelvic organ prolapse were 89.6% and 78.4%respectively.The distribution of vaginal morphology in different degrees and types of prolapse were different:vaginal morphology of 0 stage prolapse showed H-typed mainly (40/51, 78.4%), Ⅰ stage prolapse showed W-shaped (16/28 57.1%), Ⅱ,Ⅲ stage prolapse all showed non H-shaped (20/20, 100%), Ⅱstage mainly showed W-shaped (9/14), Ⅲ stage mainly showed O-shaped (3/6). Anterior pelvic organ prolapse were manifested mainly with W-shaped vaginal morphology (4/9) and middle pelvic organ prolapse mainly showed O-shaped vaginal morphology (4/7). Conclusions The abnormal vaginal morphology has the prompt value on diagnosing pelvic organ prolapse.Moreover, the different shape probably indicates the different degrees and types of pelvic organ prolapse.

Based on ninety three acetylcholinesterase inhibitors (AChEIs) which have the same mechanism of action but are different in structural characteristics, the pharmacophore model for acetylcholinesterase inhibitor was constructed by the CATALYST system. The optimal pharmacophore model with three hydrophobic units, a ring aromatic unit and a hydrogen-bond acceptor unit were confirmed (Weight = 3.29, RMS = 0.53, total cost-null cost = 62.75, Correl = 0.93, Config = 19.05). This pharmacophore model will act on the double active site of acetylcholinesterase and is able to predict the activity of known acetylcholinesterase inhibitors that are used for clinical treatment of Alzheimer's disease (AD), and can be further used to identify structurally diverse compounds that have higher activity treating with Alzheimer's disease (AD) by virtual screening.
Acetylcholinesterase ; chemistry ; metabolism ; Alzheimer Disease ; enzymology ; prevention & control ; Cholinesterase Inhibitors ; chemistry ; classification ; therapeutic use ; Drug Design ; Humans ; Models, Chemical ; Models, Molecular ; Molecular Structure ; Quantitative Structure-Activity Relationship ; Structure-Activity Relationship

PURPOSE: Breast cancer (BC) is one of the most common malignant tumors, affecting a significant number of women worldwide. MicroRNAs (miRNAs) have been reported to play important roles in tumorigenesis. The aim of this study was to determine the roles of miR-182-5p in BC progression. MATERIALS AND METHODS: The expressions of miR-182-5p and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) were measured in BC tissues and cells by quantitative real-time polymerase chain reaction or Western blot. Cell proliferation and invasion were detected by cell counting kit-8 assay and trans-well assay, respectively. The interaction between miR-182-5p and PTEN was probed by bioinformatics analysis, luciferase activity, and RNA immunoprecipitation. A murine xenograft model was established to investigate the role of miR-182-5p in BC progression in vivo. RESULTS: An abundance of miR-182-5p was noted in BC tissues and cells. High expression of miR-182-5p was associated with poor survival. Abrogation of miR-182-5p inhibited cell proliferation and invasion in BC cells. Interestingly, PTEN was indicated as a target of miR-182-5p, and its restoration reversed miR-182-5p-mediated promotion of proliferation and invasion of BC cells. Moreover, depletion of miR-182-5p suppressed tumor growth via up-regulating PTEN expression in the murine xenograft model. CONCLUSION: MiR-182-5p exhaustion blocked cell proliferation and invasion by regulating PTEN expression, providing a novel therapeutic avenue for treatment of BC.
Blotting, Western ; Breast Neoplasms ; Breast ; Carcinogenesis ; Cell Count ; Cell Proliferation ; Chromosomes, Human, Pair 10 ; Computational Biology ; Female ; Heterografts ; Humans ; Immunoprecipitation ; Luciferases ; MicroRNAs ; Real-Time Polymerase Chain Reaction ; RNA

Objective To assess the health status of rodent laboratory animals by pathological diagnosis, our lab has being take apart in investigating the quality of laboratory animals in Beijing area for years and offer some advices for standardized breeding to ensure accurate results of scientific research.This paper focuses on the analysis of laboratory rodent samples that collected in October 2014.Methods We collected the heart, liver, spleen, lung, kidney, large intestine and small intestine, and put these organs into 10%Calcium formaldehyde solution for fixation, and then prepared into two different sections for optical microscopy observation including all paraffin specimens stained with H&E and the frozen sections stained with Oil Red-O and PAS.Results The vast majority of laboratory rodents were up to standard, but there still a problem in individual units.The main problem is liver and lung disease.The rate of Hepatocyte swellingis 6%(mouse), 2.5% (rat), 8.2% (guinea pig), moreover part of them were lipidosis, according to Oil Red-O stain.the mainly problem of lung is congestion ,edema and Interstitial pneumonia ,the detectable rate of pulmonarydiseases is 15.5%(guinea pig).Conclusions The vast majority of laboratory rodents were pathologically diagnosed as healthy animals.The liver disease may be caused by improper feeding.And disease of lung may led by haze, unqualified bedding and low temperature.