Centromere protein U enhances the progression of bladder cancer by promoting mitochondrial ribosomal protein s28 expression

Bladder cancer is one of the most common types of cancer. Most gene mutations related to bladder cancer are dominantly acquired gene mutations and are not inherited. Previous comparative transcriptome analysis of urinary bladder cancer and control samples has revealed a set of genes that may play a role in tumor progression. Here we set out to investigate further the expression of two candidate genes, centromere protein U (CENPU) and mitochondrial ribosomal protein s28 (MRPS28) to better understand their role in bladder cancer pathogenesis. Our results confirmed that CENPU is up-regulated in human bladder cancer tissues at mRNA and protein levels. Gain-of-function and loss-of-function studies in T24 human urinary bladder cancer cell line revealed a hierarchical relationship between CENPU and MRPS28 in the regulation of cell viability, migration and invasion activity. CENPU expression was also up-regulated in in vivo nude mice xenograft model of bladder cancer and mice overexpressing CENPU had significantly higher tumor volume. In summary, our findings identify CENPU and MRPS28 in the molecular pathogenesis of bladder cancer and suggest that CENPU enhances the progression of bladder cancer by promoting MRPS28 expression.

Centromere protein U enhances the progression of bladder cancer by promoting mitochondrial ribosomal protein s28 expression

Bladder cancer is one of the most common types of cancer. Most gene mutations related to bladder cancer are dominantly acquired gene mutations and are not inherited. Previous comparative transcriptome analysis of urinary bladder cancer and control samples has revealed a set of genes that may play a role in tumor progression. Here we set out to investigate further the expression of two candidate genes, centromere protein U (CENPU) and mitochondrial ribosomal protein s28 (MRPS28) to better understand their role in bladder cancer pathogenesis. Our results confirmed that CENPU is up-regulated in human bladder cancer tissues at mRNA and protein levels. Gain-of-function and loss-of-function studies in T24 human urinary bladder cancer cell line revealed a hierarchical relationship between CENPU and MRPS28 in the regulation of cell viability, migration and invasion activity. CENPU expression was also up-regulated in in vivo nude mice xenograft model of bladder cancer and mice overexpressing CENPU had significantly higher tumor volume. In summary, our findings identify CENPU and MRPS28 in the molecular pathogenesis of bladder cancer and suggest that CENPU enhances the progression of bladder cancer by promoting MRPS28 expression.

Effect of immature dendritic cells derived from bone marrow on rejection of orthotopic liver transplantation in rats / 中国组织工程研究

BACKGROUND: Immature dendritic cells have strong antigen uptake and processing ability, but the lack of a variety of costimulatory molecules cannot activate and proliferate initial T cells to produce immune response, which can lead to T cell anergy, thus inducing low immune response or antigen immune specific tolerance. Simultaneously, immature dendritic cells can induce hyporeactivity of allogeneic antigen-specific T cells, thus prolonging the survival time of transplanted organs. OBJECTIVE: To investigate the effect of immature dendritic cells on liver rejection after orthotopic liver transplantation in rats and its mechanism. METHODS: According to the weight of DA and Lewis rats, the rats were randomly divided into three groups, and the liver transplantation model of DA-Lewis rats was established by “two-cuff” method. The rats of control group received no measures. The rats of cyclosporine group were treated with 10 mg/kg cyclosporine from the second day after operation, once a day, for 7 days. The rats of the immature dendritic cell group were injected with 1×106 immature dendritic cells from bone marrow of DA rats one day before operation through dorsal penile vein; the injection was repeated twice with an interval of 10 minutes. The livers of all these rats were removed 7 days after operation. Hematoxylin-eosin staining was used to observe the pathological changes. The mRNA and protein expressions of SHIP, AKT, IKK and IKβ in these three groups were detected by qRT-PCR and western blot assay. RESULTS AND CONCLUSION: (1) Compared with the control group, the survival time of cyclosporine group and immature dendritic cell group was significantly longer (P < 0.05). (2) In cyclosporine group and immature dendritic cell group, the number of infiltrating mononuclear cells and lymphocytes in the portal area of liver tissue was less, the structure of hepatic lobule was not significantly damaged, and the inflammatory cells in hepatic artery, portal vein and bile duct were significantly less than those in control group, which did not reach the level of severe acute rejection. (3) Compared with the control group, the mRNA expression of IKβ in the cyclosporine group and immature dendritic cell group was increased, while the mRNA expression of SHIP, AKT and IKK significantly decreased (P < 0.05). (4) Compared with the control group, the expression of SHIP and IKβ protein significantly increased, IKK and AKT protein significantly decreased in the immature dendritic cell group (P < 0.05). Compared with the control group, the expression of SHIP and IKK protein significantly decreased, AKT and IKβ protein expression significantly increased in the cyclosporine group (P < 0.05). (5) Results confirm that immature dendritic cells can slow down the severe acute rejection, delay the survival time of liver and reduce the T cell immune response ability of allogeneic liver transplantation.

A new self-convertible inferior vena cava filter:in vivo experimental evaluation / 中国组织工程研究

BACKGROUND:An inferior vena cava filter is an effective tool to prevent fatal pulmonary embolism. The existing filters have some shortcomings that limit their clinical application. OBJECTIVE:To evaluate the feasibility and capture efficiency of a new self-convertible inferior vena cava filter (SCF)in vivo. METHODS:L-lactide and ε-caprolactone were fused and polymerized to act as a degradable deformable switch of the filter. Medical stainless steel wire as the metal structure of the filter was combined with the degradable deformable switch to make the SCF. Eight SCFs were implanted into the inferior vena cava of eight adult Beagle dogs. The inferior vena cava angiography was performed to evaluate the release process, morphology and location of the filter. Venous angiography was performed 2 weeks later to evaluate the morphology and location of the filter and inferior vena cava patency. Detection of pulmonary embolism or other complications was performed at autopsy. RESULTS AND CONCLUSION:Eight SCFs were successfully implanted and positioned accurately with no tilt, and they were converted successfully at 2 weeks after the implantation, as assessed by the venous angiography. One of the eight SCFs migrated to the orifice of the right atrium, and caused asymptomatic inferior vena cava obstruction. The remaining SCFs were normally positioned with no tilt and local lesion or obstruction after deformation. No marked filling defect in the trunk of the pulmonary artery was shown by the pulmonary artery angiography. The autopsy report revealed that the filter arm had been endothelialized, and the inferior vena cava that was in contact with the filter arm had no obvious stenosis. Mild intimal hyperplasia, less than 1 mm in thickness, was found in the bottom of the filter arm, but it did not cause a stenosis in the lumen. No vena cava perforation, retroperitoneal hemorrhage, and injury of the surrounding viscera were found. Overall, the design of the SCF is feasible.

A new self-convertible inferior vena cava filter:in vitro experimental evaluation / 中国组织工程研究

BACKGROUND: Inferior vena cava filter is an effective way to prevent fatal pulmonary embolism. The existing filters have some shortcomings that limit the clinical application. OBJECTIVE:To evaluate the feasibility and capture efficiency of a new self-convertible inferior vena cava filter(SCF)in vitro. METHODS: The biodegradable switch was constructed of a copolymer of ε-caprolactone and L-lactide (75%/25%, PCLA75). The biodegradable switch bound together with the apices of the convertible struts to make the self-convertible filter. The deformability and capture efficiency of the filter were tested in an in-vitro flow model with three different diameters (22, 25, 28 mm). A total of 15 filters were implanted both in the vertical and horizontal positions, and the tilt angle of the filter was tested after release. To accelerate switch degradation, a lipase perfusate was injected into the flow model and refreshed every 8 hours until conversion. RESULTS AND CONCLUSION: (1) All the filters were successfully implanted without tilting, both in the vertical and horizontal positions in the three different diameter models. (2) All the 15 SCFs were converted successfully without tilting, structural damage, and displacement. (3) The capture efficiency of the SCF had significant difference between the different diameter of the models, the size of the embolus and the position of the two models (P < 0.001). The mean capture efficiency was 82.5%, and the capture efficiency exhibited a downward trend with the increase of pipe diameter, the decrease of emboli size, and the position of pipeline changing from vertical to horizontal. All these results show that the SCF is feasible and highly efficient.

Preparation, quality control and thyroid molecule imaging of solid-target based radionuclide ioine-124 / 北京大学学报(医学版)

OBJECTIVE@#To provide useful information for the further production and application of this novel radio-nuclide for potential clinical application.@*METHODS@#124Te (p,n) 124I nuclide reaction was used for the 124I production. Firstly, the target material, 124TeO2 (200 mg) and Al2O3 (30 mg) mixture, were compressed into the round platinum based solid target by tablet device. HM-20 medical cyclotron was applied to irradiate the solid target slice for 6-10 h with helium and water cooling. Then, the radiated solid target was placed for 12 h (overnight) to decay the radioactive impurity; finally, 124I was be purified by dry distillation using 1 mL/min nitrogen for about 6 hours and radiochemical separation methods. Micro-PET imaging studies were performed to investigate the metabolism properties and thyroid imaging ability of 124I.After 740 kBq 124I was injected intravenously into the tail vein of the normal mice, the animals were imaged with micro-PET and infused with CT. The micro-PET/CT infusion imaging revealed actual state 124I's metabolism in the mice.@*RESULTS@#It was been successfully applied for 200 mg 124TeO2 plating by the tablet device on the surface of platinum. It showed smooth, dense surface and without obviously pits and cracks. The enriched 124Te target was irradiated for 6 to 10 hours at about 12.0 MeV with 20 μA current on HM-20 cyclotron. Then 370-1 110 MBq 124I could be produced on the solid target after irradiation and 370-740 MBq high specific activity could be collected afterdry distillation separation and radio-chemical purification.124I product was finally dissolved in 0.01 mol/L NaOH for the future distribution. The gamma spectrum of the produced 124I-solution showed that radionuclide purity was over 80.0%. The micro-PET imaging of 124I in the normal mice exhibited the thyroid and stomach accumulations and kidney metabolism, the bladder could also be clearly visible, which was in accordance with what was previously reported. To the best of our knowledge, it was the first production of 124I report in China.@*CONCLUSION@#In this study, the preparation of 124TeO2 solid target was successfully carried out by using the tablet device. After irradiation of the 124TeO2 solid target and radio-chemical purification, we successfully produced 370-740 MBq high specific activity 124I by a cyclotron for biomedical application, and micro-PET imaging of 124I in normal mice exhibited the thyroid accumulations. Also, slight uptake in stomach were also monitored with almost nonuptake in other organs in the micro-PET imaging. The production of 124I is expected to provide a new solid target radionuclide for the scientific research and potential clinical application of our country.

The number of circulating fibrocytes of skeletal muscle in rats after contusion / 法医学杂志

OBJECTION@#To investigate the time-dependent appearance of circulating fibrocytes of skeletal muscle in rats after contusion.@*METHODS@#The model of skeletal muscle wound was established in rat. The circulating fibrocytes in contused skeletal muscle were detected by CD45 and procollagen I double immunofluorescence staining method.@*RESULTS@#In the control group, CD45- and procollagen I-positive cells were not detected in skeletal muscle. A few CD45 cells were observed aged from 6 h to 1 d after contusion. A few CD45- and procollagen I-positive cells (fibrocytes) initially gathered in injury area 3d after injury. The ratio of positive fibrocytes significantly increased 5 d after injury. The ratio of fibrocytes was highest at 7 d after contusion and then decreased. The volume of fibrocytes showed bigger with injury time increase compared with 3 d group. The expression of procollagen I and CD45 were weakened at 14d after injury.@*CONCLUSION@#The circulating fibrocytes are detected in contused skeletal muscle in time-dependent pattern. Circulating fibrocytes may be a marker in the wound age determination for contused skeletal muscle.