Objective To investigate the effects of downstream regulatory element antagonist modulator (DREAM) on the expression of glutamate transporter-1 (GLT-1) in spinal cord in rats with bone cancer pain and morphine tolerance.Methods Sixty female healthy Sprague-Dawley (SD) rats weighing 200 ～230 g were randomly divided into tow groups,group Ⅰ cancer pain (CP,n =48) and group Ⅱ Sham (S,n =12).Cancer pain in each group was produced by inoculation of syngenetic Walker 256 rat mammary gland carcinoma cells (5 × 105) to left tibia.Pain threshold to mechanical stimulus was measured before (baseline) and after the surgical procedure.From 14 d to 18 d after the inoculation of carcinoma cells,36 rats from group CP received subcutaneous injection of morphine at 3 times per day with doses increasingly from 10 mg/kg initially to 20 mg/kg,30 mg/kg,40 mg/kg,and 60 mg/kg.Equal volume of normal saline was applied to the 12 rats left in group CP.On 19th day after the carcinoma cells inoculation once subcutaneous injection of morphine at 3mg/kg was performed in all rats in group CP.From the next day,the rats in group CP ever receiving injections of morphine for 5 days were randomized into thre subgroups,including subgroups morphine tolerance (MT,n =12),vehicle (V,n =12),and RNAi (R,n =12).They were injected intrathecally with 20 μl of normal saline (NS),10 μl vehicle plus 10 μ1 NS,and 10 μ1 of DREAM-shRNA plus l0 μ1 NS,respectively,once a day for 5 days.Focusing on the affected limb,mechanical pain threshold was measured one day before surgery (T0),and at day7 (T1),day 14 (T2),day 18 (T3),day 19 (T4),day21 d (T5),day 25 (T6),and day 28 (T7) after surgery.The animals were sacrificed at day 28 after the procedure.The lumbar 4 segments in rats were removed for detection of DREAM and GLT-1.Results The mechanical threshold was significantly decreased at T1 compared to the baseline in all groups,returned to the baseline at T2 ～ T7 in group S,at T4 in group CP,and at T2 in group MT,V,and R,but remained low at T5 ～T7 in group CP,and at T3 ～T7 in group MT,V,and R.Compared to that at T1,it was decreased at T2 ～T3 and T5 ～ T7 in group CP,at T4 ～ T7 in group MT and V,and at T4 ～ T5 in group R,going back to the baseline at T4 in group CP and at T2 in group MT,V and R,and increased at T6 ～ T7 in group R.Compared to that in group S,the mechanical threshold in group CP,MT,V and R was decreased,and lower at T2 in group CP and at T4 in group MT,V and R.Compared to that in group CP,the mechanical threshold was significantly higher at T2 ～ T3 but lower at T4 in group MT,V,and R,decreased at T5 in group R and at T5 ～ T7 in group MT and V.The mechanical threshold was increased at T6 ～ T7 in group R and higher than that in groups MT and V.The expression of DREAM,compared to that in group S,was down-regulated in other groups.Compared to group CP,increment was shown in groups MT and V,and decrease was exhibited in group R.It was cut down in group R compared to that in groups MT and V.Compared to group S,GLT-1 was decreased in other groups.It was down-regulated in groups MT,V and R compared to group CP.Conclusions DREAM is involved in the development of allodynia after morphine tolerance in rats with bone cancer pain.No evidence in this study supports a link between DREAM and GLT-l in spinal cord.

Aneuploidy ; Gene Rearrangement ; Glutathione S-Transferase pi ; metabolism ; Humans ; Male ; Methylation ; Neoplasm Grading ; Neoplasm Staging ; Neoplasms, Multiple Primary ; genetics ; metabolism ; pathology ; surgery ; Oncogene Proteins, Fusion ; genetics ; Prostate-Specific Antigen ; metabolism ; Prostatic Intraepithelial Neoplasia ; genetics ; pathology ; Prostatic Neoplasms ; genetics ; metabolism ; pathology ; surgery

Aurora-B as an important kinase to adjust the cell normal mitosis is a potent target for cancer treatment. Aurora-B is overexpressed in a broad range of tumor and tumor cells are more sensitive while Aurora-B is inhibited. Due to the key role of the Aurora-B in cell mitosis, the development of its inhibitors is becoming more and more important. Several small molecules inhibit with a similar efficacy both Aurora-A and Aurora-B, however, in most cases the effects resemble Aurora-B disruption by genetic methods, indicating that Aurora-B represents an effective therapeutic target. There were several Aurora-B kinase inhibitors which had entered the clinics and displayed good antitumor activity. In this review, we will outline the functions of Aurora kinase B in normal cell division and in malignancy. We will focus on recent preclinical and clinical studies that have explored the mechanism of action and clinical effect of Aurora-B inhibitors in cancer treatment.

Apoptosis ; Down-Regulation ; Electron Transport Complex IV ; chemistry ; genetics ; metabolism ; Humans ; Mitochondria ; metabolism ; Mutation ; Neoplasms ; genetics ; metabolism ; pathology

BACKGROUND:Studies have shown that thymosinβ4 can improve the anti-apoptotic ability of a variety of cells, but the reports describing the changes in the anti-apoptotic ability of bone mesenchymal stem cells modified with thymosinβ4 gene in the hypoxic environment are rare.
OBJECTIVE:To observe the change in the apoptotic rate of bone mesenchymal stem cells modified with thymosinβ4 gene in the hypoxic environment, and to explore whether thymosinβ4 affects the apoptosis of bone marrow mesenchymal stem cells via regulating the expression of Bax and Bcl-2.
METHODS:Bone marrow mesenchymal stem cells were transfected with the recombinant lentiviral vector over-expressing the thymosinβ4 gene, and then we observed the expression of thymosinβ4 using western blot assay. cells were divided into three groups:thymosinβ4 transfection group, control virus group, and untreated group. Al three groups were placed in a hypoxic environment. The apoptotic rate of bone marrow mesenchymal stem cells was evaluated by the flow cytometry assay. The expression of Bax and Bcl-2 protein was detected by western blot.
RESULTS AND CONCLUSION:Thymosinβ4 gene was expressed successful y in the bone marrow mesenchymal stem cells showed by the western blot. The apoptotic rate of bone marrow mesenchymal stem cells in the hypoxic environment was lower in the thymosinβ4 transfection group than the control virus group and untreated group;while there was no difference between the latter two groups. Western blot results showed that the expression of Bcl-2 protein was higher in the thymosinβ4 transfection group than the control virus group and untreated group, and the expression of Bax protein was lower in the thymosinβ4 transfection group than the control virus group and untreated group. No difference in the expression of Bax and Bcl-2 was found between the control virus group and untreated group. These findings indicate that thymosinβ4 overexpression can improve the anti-apoptotic ability of bone mesenchymal stem cells modified in the hypoxic environment, and its possible mechanism is through regulating the expression of Bax and Bcl-2 protein.

Accidents, Occupational ; Adolescent ; Adult ; Ammonia ; poisoning ; Female ; Humans ; Male ; Young Adult

Objective To observe the curative effect of low melocular weight heparin(LMWH) on the hypercoagulability in acute Kawasaki disease(KD).Methods Forty-six patients were diagnosed KD.Twenty-two cases out of all KD patients whose serum concentration of whether platelet(PLT) or fibrinogen(FIB) was significantly increased or who were found thrombus in their coronary artery by ultrasonic Doppler were treated with LMWH by subcutaneous injection once every day for 7-10 days.All the patients were divided into 2 groups accor-ding to whether using LMWH or not:H group(using LMWH) and NH group(no using LMWH).It were detected before and after treatment that included thrombin time(TT),activated partial thromboplastin time(APTT),international normalized ratio(INR),FIB,plasma mucosity,erythrocyte sedimentation rate(ESR),hematocrit(HCT) and situation of haemorrhage.Results 1.Before treatment,PLT and FIB of patients in H group were significantly higher than those in NH group(Pa

The feasibility of bone marrow stromal cells autologous transplantation for rabbit model of dilated cardiomyopathy induced by adriamycin was studied. Twenty rabbits received 2 mg/kg of adriamycin intravenously once a week for 8 weeks (total dose, 16 mg/kg) to induce the cardiomyopathy model with the monitoring of cardiac function by transthoracic echocardiography. Marrow stromal cells were isolated from cell-transplanted group rabbits and were culture-expanded on the 8th week. On the 10th week, cells were labeled with 4,6-diamidino-2-phenylindole (DAPI), and then injected into the myocardium of the same rabbits. The results showed that viable cells labeled with DAPI could be identified in myocardium at 2nd week after transplantation. Histological findings showed the injury of the myocardium around the injection site was relieved with less apoptosis and more expression of bcl-2. The echocardiography found the improvement of local tissue movement from (2.12+/-0.51) cm/s to (3.81+/-0.47) cm/s (P<0.05) around the inject site, but no improvement of heart function as whole. It was concluded bone marrow stromal cells transplantation for dilated cardiomyopathy was feasibe. The management of cells in vitro, the quantity and the pattern of the cells transplantation and the action mechanism still need further research.

Objective To investigate the effects of two biovars of ureaplasma urealyticum on leukocyte concentration and sperm motion parameters.Methods Sperm motion parameters were analyzed with computer-aided sperm analysis (CASA).Leukocytic number of semen was measured with benziding-perxidase staining.Culturing and real-time polymerase chain reaction (RT-PCR) was used to identify biovars of U.urealyticum in the semen.Results Sperm motion parameters including mean curvilinear velocity (VCL), mean straight-line velocity (VSL), mean average path (VAP) , and mean beat Cross frequency (BCF) showed significant difference between infertile and normal group (P ＜0.05).Biovar Ⅱ infected men displayed significant increase in leukocyte counts (P ＜ 0.001).When compared to uninfected group,the sperm motion parameters showed significant decreases of VCL, VSL, VAP, mean percentage lineality (LIN), and swing(WOB) in biovar Ⅱ (P ＜ 0.05).Conclusions Biovar Ⅱ has closer relationship with leukocyte elevation and sperm motion impairment.

Objective To explore the feasible approach for establishment of a liver cancer model induced by N-nitrosodiethylamine(DENA)with Sprague-Dawley rat,and to provide ideal animal model for imaging diagnosis and interventional therapy.Methods One-hundred and forty male SD rats were administrated with 0.95 g/L DENA for 10 weeks,and MRI was performed for inspecting pathological changes of rat livers on the following week.When the liver tumor was proved then the rat will be the candidate for sequential procedures,otherwise the animal continued under observation until next MRI examination after 4 weeks.DSA was done in 64 rats'for detecting blood supply of liver tumors.Animals were sacrificed with an overdose of chloral hydrate,The representative tumor tissues were fixed in 10% formalin and 2.5% glutaraldehyde for light and electron microscopy analysis respectively.Alpha fetoprotein(AFP) and hepatocyte were assaied by immunohistochemistry technique in order to identify intrinsic trait of the harvested tumors.Results The earliest induced tumor was detected on 11th week and the latest was on 20th week by MRI,and the median period was 13.9 weeks.Tumor size ranged from 2 mm to 40 mm in diameter. The rate of single and multi-induced tumor was 9.7%(7/72)and 90.3%(65/72),respectively.87.7% (57/65)" of the induced multiple tumors was with hepatocirrhosis and 18.1% of these tumors combined with extrahepatic neoplasm or metastasis.Plenty blood supply was proved by DSA in most of those tumors. Tumors not only derived from hepatocyte but also manifested positive expression of AFP.Histological types of these tumors include hepatocellular carcinoma(HCC)(92.0%,66/72),intrahepatic cholangiocarcinoma (ICC)(4.0%,3/72),and combined HCC and ICC(4.0%,3/72),respectively.Electro-microscope analysis indicated that cytoplasm and organelle of induced tumors were abnormal distinctly compared with those of non-carcinomatous cells.Conclusion DENA can induce ideal rat liver cancer as a feasible animal model,MRI is the best approach for scrutinizing pathological changes of rat livers during induced period.