ABSTRACT
The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300-β-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.
ABSTRACT
Objective To analyze the doctors' working enthusiasm and its influencing factors on county level hospitals.Methods 17 seminars were held in 8 counties of 3 provinces to investigate 1055 doctors with questionnaires, analyzing the three scales of working enthusiasm, working enthusiasm influencing factors, and changes since the 2009 new healthcare reform.Results Working enthusiasm comprises inner drive, working pleasure, work recognition and external recognition, and inner drive of which is found to play the most important part, with 20.55％ variance contribution.Among the six dimensions of the influencing factors, working conditions rank the highest with 19.46％ variance contribution.Conclusion Optimized measures in the healthcare reform, better working conditions and social environment can improve working enthusiasm of these doctors.
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AIM To study the hemolyzation of a highly active anti complementary protein (cobra venom factor, CVF) isolated from the venom of Naja kaouthia distributed in the south of Yunnan Province, China. METHODS Guinea pig red blood cell and serum were employed to evaluate the hemolyzation of this anticomplement factor, and the effects of temperature, pH, various bivalent mental ions and EDTA on its hemolyzation were investigated. RESULTS This anticomplement factor possessed hemolytic activity of 1 391 kU?g -1 protein. It showed high stability to heat, alkalinity and acidity. Ca 2+ , Mg 2+ , Mn 2+ promoted the hemolyzation of this anticomplement factor at 1, 2 and 5 mmol?L -1 . Zn 2+ , Co 2+ also promoted the hemolyzation of this anticomplement factor at 1 and 2 mmol?L -1 , but inhibited the hemolyzation at 5 mmol?L -1 . Cu 2+ strongly inhibited the hemolyzation at 1, 2 and 5 mmol?L -1 . EDTA also strongly inhibited the hemolyzation of this anticomplement factor. CONCL- USION The anticomplement factor showed hemolytic activity. This ability could be influenced by bivalent metal ions and EDTA, but rather stable when temperature or pH value changed.
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The effect of anisodamine(654-2),aspirin(acetylsalicylic acid, ASA),prostacy-clin (PGI2)-like substance on whole blood platelet aggregation induced by adenosine diphos-phate ( ADP ) , arachidonic acid ( AA ) and ag-gregoserpentin of Trimersurus mucrosqumatus venom (TMVA) is reported, We found that ADP,AA and TMVA caused a dose-related increase in whole blood platelet aggregation, and the impedance technique was a sensitive method to evaluate the response of platelet in physiological condition. 654-2 could promote whole bloodplatelet aggregation induced by ADP, while ASAor PGI2-like substance could obviously inhibit the whole blood platelet aggregation induced by ADF or AA, but they failed to prevent TMVA-induced aggregation, suggesting that TMVA might mediate third pathway of platelet aggregation similar to platelet activiting faetor(PAF). Furthermore, the platelet stimulated by ADP or AA was still activated by TMVA, the mechanism of which remains to be studied.
ABSTRACT
Objective:To investigate the pahtogengesis and pathology of delayed xenograft rejection (DXR) after pig to rhesus monkey heart xenotransplantation.Methods:Heterotopic xenogeneic heart transplantation in the abdominal cavity was performed using piglet as donors.4 monkeys were used as recipients.Complete complement depletion was achieve in the recipients treated with repetitive doses of a high activity cobra venom factor (Y CVF).The recipients were immunosuppressed with a combination of cyclosporine A,cyclophosphamide and steroids.Sera were analyzed for C3,C4 levels and complement activity and anti pig endotheliocyte xenoantibody.The graft were examined histopathologically and immunohistochemically for C3,C4,C5b 9,IgM,IgG,necrosis factor alpha (TNF alpha),intercellular adhesion molecule 1 (ICAM 1),CD57 (NK cells),CD68 (macrophages),CD4 and CD8.Results:The xenografts survived 8,10,13,13 days respectively and all grafts occoured DXR.Venular thrombosis was outstanding feature within DXR xenografts,complicated with interstitial edma,local hemorrhage and myocardial necrosis,with mild to moderate cellular infiltration.The serum C3 levels and complement activity almost decreased to 0 from the day of transplantation due to Y CVF,the C4 level began to decrease 2 4 days before the cardic xenografts losing their function.The anti pig endotheliocyte xenoantibody also decreased after transplantation,and slightly increased during DXR,all rejected xenografts showed C3,C4,C5b 9,IgG and IgM deposits in different degree.Large numbers of macrophages (50% of total leukocytes) were found infiltrating the entire xenograft,a few natural killer cells (8%～10%),some of CD4+T cells (15%) and CD8+T cells (25%) were detcted also,up regulation of ICAM 1 on the graft endothelial cells and TNF alpha in the interstitial were demonstrated in the rejected heart.Conclusion:Both Humor and cell mediated immunologic reaction may play an important role in pahtogengesis of DXR. [