As a tumor suppressor, p53 is activated by numerous cellular and environmental signals, and plays a criticalrole in the cell cycle regulation, cell apoptosis and senenscence. The murine double minute (MDM)2 and double minute mu?rine 4 (MDMX) are two important regulators. MDMX is a p53 binding protein with strong sequence homology to MDM2, but lacks ubiquitin ligase activity, and which is unable to target p53 for proteasomal degradation. MDMX regulates p53 activity through its binding with p53 and its postranscriptional modification. MDMX in the closed and open structure binds to p53 to regulate its activity. As the main partner of MDMX, casein kinase 1 alpha (CK1α) disrupts the intramolecular binding in MD?MX in the cooperation to regulate p53 activity. The process of MDMX and CK1αin the regulation of p53 is multi-step and complicated. In this paper the mechanism of MDMX and CK1αin the regulation of p53 protein was reviewed.

Objective To investigate the association of genetic polymorphism in the advanced glycation endproduct (RAGE) gene with genetic susceptibility to ischemic stroke.Methods A case-control study was conducted with 124 ischemic stroke patients serving as the stroke group and 125 healthy volunteers serving as the control group.Three common polymorphisms in the RAGE gene,82G/S (rs2070600),-429T/C (rs1800625) and-374T/A (rs1800624),were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP) method.The association between the three polymorphisms and genetic susceptibility to ischemic stroke was further analyzed by logistic regression analysis.Results The body mass index (BMI),diastolic blood pressure,blood lipids levels,and the percentage of smokers were significantly higher in the stroke group than in the control group (each P＜0.05).At the 82 position,the frequencies of the genotypes GG,GS and SS were 10％,48％ and 42％,respectively.At the 429 position,the frequencies of the genotypes TT,TC and CC were 15％,44％ and 41％,respectively.At the 374 position,the frequencies of the genotypes TT,TA and AA were 8％,41％ and 50％,respectively.After adjusting for confounding factors including age,gender,smoking and blood pressure,the genotype frequencies of SS and S alleles at 82G/S of the RAGE gene were higher in the stroke group than in control group (SS:OR=2.14,95％ CI:1.37-3.51;S:OR=1.96,95％ CI:1.24-3.34),while no significant differences of genotype frequencies of the 429T/C and-374T/T polymorphisms were observed between the stroke group and the control group (each P＞0.05).Conclusions The 82G/S gene polymorphism of the RAGE gene has correlations with ischemic stroke in the Henan Han population,with the S allele as the risk factor for ischemic stroke.However,no clear association between the 429T/C or-374T/A polymorphisms of the RAGE gene and ischemic stroke is identified in the Han population.

Humans ; Laparoscopy ; Proctectomy ; Rectal Neoplasms/surgery* ; Rectum/surgery* ; Transanal Endoscopic Surgery

Objective To evaluate the usage of renoportal anastomosis in the liver transplanta- tion.Method The successful experience about renoportal anastomosis for portal vein reconstruction in liver transplantation was reported,and related literature reviewed.Results Including our case,there have been 13 cases of liver transplantation using renoportal anastomosis for portal vein reconstruction. Among these patients,8 cases were complicated with diffuse portal vein thrombosis,and 10 cases had a splenorenal shunt(spontaneous shunt in 3 and surgical shunt in 7).Complications related to portal vein hypertension occurred in 3 cases(transient ascites in 2 cases and severe digestive bleeding in 1 case)after liver transplantation.There were 3 deaths which were not related to renoportal anastomo- sis.Conclusion Renoportal anastomosis is a safe and feasible technique in liver transplantation for the patients with diffuse portal vein thrombosis or with splenorenal shunt(spontaneous or surgical shunt).

Objective To investigate the depressing effect of antigene peptide nucleic acid (AGPNA)on the k-ras gene expression of human pancreatic cancer Patu8988 cells, the inducing apoptosis effect on Patu8988 cells, and the biodistribution characteristics in nude mice bearing xenografts using 188Re-k-ras-AGPNA.Methods The expression level of k-ras mRNA and the expression ratio of k-ras protein in Patu8988 cells transfected with AGPNA was measured by RT-PCR and flow cytometry ,respectively. The degree of cellular apoptosis 3 to 5 d after treating Patu8988 cells with 188Re-k-ras-AGPNA or 188ReO4- was determined by flow cytometry. For biodistribution study, 58 nude mice bearing Patu8988 cell xenografts were divided into two groups: intratumoral injection of 188Re-k-ras-AGPNA (Group A) and 188ReO4- (Group B). At different time points, the mice were sacrificed and organs of interest were excised, weighted and counted by a gamma counter. The organ uptake was calculated as a % ID/g and the absorbed doses of organs were calculated. One-way analysis of variance was used. Results After transfected with 1 nmol/ml AGPNA, the k-ras mRNA gray scale ratio and the expression ratio of k-ras protein were 1.00 ± 0.39 and (15.05 ± 5.07)%, respectively. They were significantly lower than those of the control group with 1.86 ± 0.07 and (24. 38 ± 5.40) % (F = 2. 545, 5. 327, P<0. 05). At 4 and 5 d after treatment in Group A, float cells' apoptosis ratios were (26.30 ± 7.45) % and (27.90 ± 10. 38) %, respectively. Tumors were the major distribution site in Group A with uptake of (37.47 ±21.31), (35.96 ±7.80) and (15.46 ±4.93) %lD/g at 1 h, 1 d and 7 d after intra-tumor injection, respectively. The absorbed dose of tumor was 15 569 mGy/MBq. Condusions Transfection with k-ras-AGPNA on Patu8988 cells may inhibit k-ras expression at mRNA and protein expression level, and 188Re-k-ras-AGPNA can induce apoptosis of Patu8988 cells.Tumor is the major distribution site in nude mice bearing human pancreatic cancer xenografts after intratumoral injection of 188Re-k-ras-AGPNA.

Objective To observe the effect of lovastatin on plasminogen activator inhibitor -1 (PAI-1) and collagen type Ⅳ in rats with glomerularsclerosis induced by adriamycin,and to discuss its mechanism of protective effects on kidneys.Methods Twenty-four male Wistar nephritic rats induced by adriamycin were randomly divided into 3 groups:control,hyperlipidemia and lovastatin treatment group.They were fed 12 weeks.Urinary protein excretion and serum lipid were assayed,then renal glomerularsclerosis index,the expression of PAI-1 and collagen type Ⅳ were observed.Results Serum total cholesterol,triglycerides,low-density lipoprotein,urinary protein excretion,renal glomerularsclerosis index were significantly lower in treatment group than those in hyperlipidemia group.Expression of PAI-1 and collagen type Ⅳ,and number of foamcells were also sharply lower in treatment group than those in hyperlipidemia group.Conclusions Lovastatin not only reduces proteinuria,improves renal function,but also modulates glomerularsclerosis by inhibiting activity of PAI-1 and decreasing accumulation of collagen type Ⅳ.The mechanism of renal protective effect is independent of a reduction of circulating cholesterol.

BACKGROUND:Nano-size inorganic filling greatly improves mechanic characteristic of composite resin.However,its effects on pulp tissue remain unclear.OBJECTIVE:To evaluate the biocompatibility of FiltekTM Z350 nano-composite resin on dog pulp tissue by means of histology observation.DESIGN,TIME AND SETTING:Randomized control animal experiment was performed at the animal experiment center of Fuzhou General Hospital,Nanjing Military Area Command of Chinese PLA from April 2007 to April 2008.MATERIALS:Sixty healthy teeth from three adult male beagle dogs were recruited in this study.METHODS:Buccal Class V deep cavities were prepared in beagle dogs,which were then divided into four groups at random.FiltekTM Z350 resin,Dyract AP compomer and TPH resin were used to restore the cavities in three testing groups and glass ionomer cement was used as control.All cavities were treated with Clearfil SE BOND before filling.Intact healthy teeth were used as blank control.MAIN OUTCOME MEASURES:The pulp condition of each tooth was studied histologically.The remaining dentine thickness of each cavity was measured.RESULTS:After 7 days,mild inflammatory response was observed in most of the specimens.After 30 and 90 days,normal histological characteristics were observed in almost all specimens except TPH resin group.The histological structure disturbance of dentin cell layer emerged in some specimens of TPH group,which was higher than other testing groups(P 0.05).CONCLUSION:FiltekTM Z350 nano-composite resin has similar biocompatibility as Dyract AP compomer and glass ionomer cement,better than TPH resin.

Objective To determine the roles of MyD88 and Trif,critical adaptor proteins for TLR signaling,in production of donor-specific antibodies (DSA) and memory T cells in a presensitized mouse cardiac transplant model.Methods Skin grafts from Balb/c mice were transplanted into either wild type B6 mice or B6 Myd88 and Trif double knockout mice (Myd88/Trif DKO).The recipients were subsequently transplanted heterotopically with cardiac grafts from the same donors two weeks after skin transplantation.Plasma DSA levels and spleen phenotypical analysis were performed prior to heart transplant or at time of cardiac rejection by using flow cytometry.Results Recipients presensitized with skin grafts developed accelerated cardiac allograft rejection in the absence of Myd88 and Trif.However,plasma DSA,especially IgG2,was significantly decreased (P＜0.05) in Myd88/Trif DKO mice,compared to that in Wild Type mice at 2nd week after skin transplantation.The production of DSAs including all IgG subtypes was further reduced 3 days following heart transplantation in the Myd88/Trif DKO.In addition,MyD88/Trif DKO mice had impaired ability to generate memory T cells,as percentages of both CD44hi CD4+ and CD44hi CD8+ were significantly lower in the DKO than in Wild Type mice (P＜0.01,P＜0.05).Conclusion Simultaneous ablation of MyD88 and Trif in recipients significantly decreases the production of serum DSAs and spleen memory T cells following allogeneic skin and heart transplantation,supporting a crucial role of TLR signaling in adaptive immune responses in organ transplantation.

BACKGROUND:Compared with smooth titanium, titania nanotubes cannot only induce mesenchymal stem cels osteogenic differentiation and promote bone integration, but also be used as drug nanocarriers. OBJECTIVE:To prepare dexamethasone-loaded titania nanotube system and to test its drug release characteristics. METHODS:Titania nanotubes were prepared by electrochemical anodic oxidation, and dexamethasone was dripped onto the prepared titania nanotubes. Subsequently layer by layer self-assembly technology was employed to fabricate gelatin/chitosan multilayered structure on the prepared samples. Scanning electron microscope and contact angle test were carried out during the process of building the gelatin/chitosan multilayered structure. The drug release was measured by a ultraviolet spectrophotometer. RESULTS AND CONCLUSION:Under the scanning electron microscopy, the fabricated titania nanotubes had integral structure with even tube size of about 70 nm and arranged regularly, and the nanotubes were completely covered and sealed by the gelatin/chitosan multilayered membrane. Contact angle test results showed that ever since the fifth layer, contact angles changed alternately and displayed a zigzag profile. Ultraviolet spectrophotometer test results showed that when cultured for 3 hours, the cumulative drug release was about 32.7% and demonstrated an initial burst folowed by sustained release. When cultured for 24 hours, the cumulative drug release about 52.3%. However, after cultured for 7 days, little drug release was detected. And there was about 8.0%-10.0% dexamethasone of initial loading preserved in nanotubes.

Adult ; Female ; Fungi ; Humans ; Mycoses ; Sinusitis ; microbiology