Objective To study whether IL-1β, a catabolic factor of cartilage metabolism, induces premature senescence of articular chondrocytes, and whether caveolin-1 mediates IL-1β-induced cellular senescence. Methods Cultured human articular chondrocytes were stimulated with 10 ng/ml IL-1β. Cellular senescent phenotypes were analyzed by cellular morphology, cell growth arrest (flow cytometry), telomere erosion (Southern blotting), life span (population doublings), and specific senescence-associated β-galac-tosidase (SA-β-Gal) activity. Expression level of caveolin-1 was modulated by anti-sense oligunucleotide or transfection of caveolin-1 gene. Caveolin-1 protein was analyzed by Western blotting. Results Incubation of chondrocytes with IL-1β markedly increase the percentage of cells in G0/G1 phase and reduce the percentage in S phase. Single stimulation with IL-1β enables chondrocytes to become big and flat, and SA-β-Gal activity in chondrocytes is enhanced. Repeated stimulation with IL-Iβ resulted in accelerats erosion of mean telomere length, and shortens life span. Down-regulation of caveolin-1 with anti-sense oligonucleotide significantly inhibits the features of chondrocytes senescence induced by IL-1β. In contrast, caveolin-1 overexpreasion enhanced SA-β-Gal activity in the chondrocytes. Conclusion IL-1β induces features of stress-induced premature senescence and telemere-dependent replicative senescence of articular chondrocytes, which is mediated by caveolin-1. These data suggest that IL-1β induces premature senescence of articular chondro-cytes by upregulation of caveolin-1, which facilitates the development of osteoarthritis.

The effect of rhGM-CSF/IL-3 on apoptosis of Ara-C-induced myeloid leukemic cell line HL- 60 was investigated. The results indicated that treatment with rhGM-CSF/IL-3 in combination with Ara-C significantly inhibited the colony growth of HL-60 and enhanced the oligonucleosomal DNA fragmentation as compared with Ara-C alone. The Ara-C mediated apoptosis rates of HL-60 cells treated with rhGM-CSF/IL-3 fusion protein alone were markablely improved compared with treatment with rhIL-3 plus rhGM-CSF, it was noted that the Ara-C mediated of apoptosis normal peripheral white blood cells was less affected by rhGM-CSF/IL-3. It suggested that rhGM-CSF/IL-3 could be used as a possible curing drug during the phase of induced remission of leukemia.

Objective:To investigate the correlation between arterial baroreceptor reflex (ABR) function and target organ dam age (TOD) in spontaneously hypertensive rats (SHR) .Methods:Twenty- four- hour blood pressure (SBP and DBP ) ,blood pressure variability (BPV ) ,heart rate (HR ) and HR variability (HRV ) were m easured in conscious, unrestrained SHR and Wistar- Kyoto (WKY ) rats.ABR function control of heart period (ABR- HP) and blood pressure (ABR- BP) were determined respectively.Hypertensive TOD was evaluated according to the scoring system.Results:SBP, DBP and their BPV were significantly increased in SHR compared with those of WKY rats.No difference of HR was found between the 2 strains,but HRV was significantly decreased in SHR when com pared with WKY rats.ABR- HP and ABR- BP of SHR were significantly decreased compared with those of WKY rats (P

AIM To investigate the changes of vascular systiolic/relaxant function in sino-aortic denervated rats. METHODS Male Sprague-Dawley rats were underwent sino-aortic denervation (SAD). The sinoaortic denervated (SAD) rats were adopted as a model of arterial baroreflex deficit. SAD, isolated aortic-denervated (AD) and isolated sinus-denervated (SD) rats were instrumented chronically to record blood pressure (BP), heart rate (HR), BP variability (BPV), HR variability (HRV), arterial baroreflex function control of heart period (ABR-HP) and BP (ABR-BP). The vascular maximum contractile/relaxant function was determined through cumulative venous injection of phenylephrine (SBP max ) and nitroprusside(DBP min ) both after ganglionic blokade. RESULTS Acute SAD(1 week after operation) caused hypertension and tachycardia in rats. Eighteen weeks after operation, BP and HR values in SAD and SD rats were not different from those in sham-operated rats, but AD rats were hypertensive compared with control group. Though the 24 h mean BP values of chronic (18 weeks after operation) SAD rats was not different from those in the sham-operated rats, 24 h BPV of SAD rats was significantly higher when compared with sham-operated rats. ABR function in the acute SAD rats was significantly decreased when compared with sham-operated rats, whereas in chronic SAD rats, both ABR-HP and ABR-BP were higher than those in acute SAD rats, but were still significantly lower than those in control groups. 18 weeks after operation, ABR function in SAD and AD rats were significantly decreased when compared with those in SD and control groups. SBP max after phenylephrine and DBP min after nitroprusside were significantly higher in SAD, AD and SD rats than in control group. ABR function was negatively correlated to DBP min ( r =-0.677 for ABR-HP, and r =-0.681 for ABR-BP; P

Objective:To study the changes of serum IL 1?,IL 6,IL 8,TNF ? and sIL 2R and its relationship with disease activity in adult Still disease patients.Methods:Serum levels of IL 1?,IL 6,IL 8,TNF ? and sIL 2R were assessed by ELISA in 18 adult Still disease patients before and one month after treatment with prednisone.Results: Active adult Still disease patients had significant elevated erythrocyte sedimentation rate (ESR) and serum levels of C reactive protein (CRP),IL 1?,IL 6,IL 8,TNF ? and sIL 2R.After one month treatment with prednisone,ESR and serum levels of CRP,IL 6,TNF ? and sIL 2R significantly decreased.There was a significant correlation between ESR values and serum IL 6,TNF ? and sIL 2R levels,and between serum CRP levels and IL 6,TNF ? and sIL 2R levels.Serum IgG,IgA and IgM levels in active adult Still disease patients were similar to those in healthy controls.Conclusion: There are no changes in serum immunoglobulins but significant increases of serum IL 1?,IL 6,IL 8,TNF ? and sIL 2R levels in active adult Still disease.Serum levels of IL 6,TNF ? and sIL 2R are related to the activity of adult Still disease.

Objective To evaluate the analytical performance of ARCHITECT-i2000SR chemiluminescence analyzer in detec-tion of HBsAg,HIV-antibody,TP-antibody and HCV-antibody.Methods Validated the precision,carryover,ference interval of alpha-fetoprotein and linearity performance of ARCHITECT-i2000SR.The same specimens were tested by both CMIA and ELISA,and the results were compared and analyzed.Results The precision,carryover and ference interval of alpha-feto-protein of HBsAg,HIV-antibody,TP-antibody and HCV-antibody were within the range provided by the manufacturer for ARCHITECT-i2000SR.The theoretical and measured values of HBsAg were:Y = 1.102X - 6.678 6 (r = 0.995 5,P <0.05),the range of linearity 1.08~208.6.The sesult was very good for the four blood index by both methods.Conclusion The basic performances of ARCHITECT-i2000SR were consistent with the data provided by the manufacturer,so it canbe used to inspect the clinical samples and the sasults were credible.

Protease activated receptor-2(PAR-2)is a G-protein-coupled receptor.Recent studies indicate that PAR-2 is mainly expressed in leukocytes and activated by pancreatin and(or)tryptase,which subsequently induces inflammation through degranulation of leukocytes.Activation of PAR-2 in leukocytes is possibly involved in the pathogenesis of rheumatoid arthritis.

Objective To investigate the effects of Skp2 overexpression on the sensitivity of troglitazone (TRG) in breast cancer cells and to devote to develop a novel drug for increasing the patient survival rate and eventually reaching the cure goal .Methods The transcription activities of PPARγ were analyzed on peroxisome proliferators response element(PPRE) luciferase reporter .The flow cytometry analysis and CCK‐8 assay were adopted to study that overexpression of Skp2 was associated with resistance to TRG‐mediated inhibition growth and apoptosis of breast cancer cells .Results Our study found that overexpression of Skp2 inhibi‐ted the transcriptional activity of the endogenous PPARγ and resisted to TRG‐mediated inhibition growth and apoptosis of breast cancer cells .Conclusion Overexpressed Skp2 breast cancer cells is able to be resistant to TRG‐induced sensitivity of breast cancer cells .Furthermore down‐regulating Skp2 will significantly enhance the growth inhibition of TRG on breast cancer cells .

Objective This study was designed to investigate the expression changes of osteopro-tegerin (OPG), tartrate-resistant acid phosphatase (TRAP) and vascular endothelial growth factor (VEGF) mRNA in collagen induced arthritis(CIA) rats. Methods After CIA was induced in Sprague-Dawley rats, the experimental animals were treated with PBS or rAAV-EGFP or rAAV-hOPG (100 μl/day) intra-articular injection for 10 days. Messenger RNAs (mRNAs) were obtained from CIA synovium 40days after first immun-ization. Reverse transcriptase-polymerase chain reactions (RT-PCR) were carried out to detect the mRNA encoding OPG, TRAP, VEGF and β-actin, which acted as inner control. The genes detected clearly by RT-PCR were quantified using real-time PCR. Results The expression of all genes was confirmed by specific single bands in RT-PCR. Real-time PCR showed that the expression levels of TRAP and VEGF were increased, whereas those of OPG mRNA were decreased in CIA group compared with normal controls. The intra-articular gene transduction markedly increased the gene copies of OPG by 128.21% (P<0.01). The expression change of OPG in synovium also caused the decrease of the expression levels of TRAP and VEGF by 58.79% (P<0.01)and 17.85% (P>0.05) respectively, however, the expression change of VEGF was not statistically significant. Conclusion OPG gene mediated by rAAV can be successfully tranfered to knee joint synovium in vivo. The results of this study suggest that gene transfer using rAAV-OPG may be a feasible and effective therapeutic approach to treat or prevent joint destruction in inflammatory arthritis.

Objective Using an in vivo adeno-associated virus(AAV)-mediated gene transfer technique,this study was designed to evaluate the protective effects of human osteoprotegerin(OPG)transgene against joint destruction in collagen induced arthritis(CIA)model.MethodsAfter CIA was established in the Sprague-Dawley rats,the experimental animals were treated with PBS or rAAV-EGFP or rAAV-hOPG (100μl/d)intra-articular injection 25 days after arthritis induction for 10 days.Paraffin-embedded joints were then analyzed histologically.The joint destruction was evaluated by Larsen Score.The protein expression of OPG,IL-1,MMP-3 was identified by enzyme-linked immunosorbent assay(ELISA).Results Suecessful trans-gene expression was confirmed by the detection of OPG by ELISA and positive fluorescence of the frozen joint section. Image analysis revealed that the expression of OPG significantly protected against joint destruction by 30% compared with the CIA group. Conclusion OPG gene transfer mediated by rAAV effectively protects against bone destruction induced by CIA model. Those data suggest that gene transferring using rAAV-OPG may be a feasible and effective therapeutic approach to treat or prevent joint destruction in inflammatory arthritis.