Effects of adenovirus-mediated gene transfer of ICOSIg fusion protein on experimental autoimmune myocarditis in Lewis rats / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the effects of adenovirus vector-mediated gene transfer of ICOSIg fusion protein on experimental autoimmune myocarditis (EAM) in Lewis rats.</p><p><b>METHODS</b>Expression vector containing ICOSIg (p-Adeno-ICOSIg) was constructed by fusion of human ICOS and IgGFc segment. Adenovirus vector was digested by PacI enzyme and transfected into HEK 293 cells. Adenovirus expressing ICOSIg was produced. EGFP was constructed into adenovirus vector and used as control. EAM was induced in Lewis rats by injection of porcine cardiac myosin. All immunized Lewis rats were divided into 4 groups. Group A (n = 15) and B (n = 15) received adenovirus containing ICOSIg on day 0 and day 14 respectively to study the effects of costimulatory molecules gene therapy on T cell activation and inflammation; group C (n = 10) and group D (n = 10) received adenovirus containing EGFP on day 0 and day 14 respectively as controls. Group E (n = 10) was normal controls that did not receive immunization. On day 28, all rats were killed after echocardiography examination. Histopathological examination was performed to observe myocardial inflammation. Protein levels of ICOS, ICOSL, B7-1 and B7-2 were detected by Western blot. INF-gamma, IL-2 and IL-4 mRNA were determined by realtime RT-PCR.</p><p><b>RESULTS</b>On day 28, cardiac function was significantly improved and myocardial inflammation significantly attenuated in group B compared to group A, C and D (all P < 0.05). B7-1 expression at protein level was significantly lower in group B than that of group C (P < 0.05). ICOS and ICOSL expressions at protein level were significantly decreased in both group A and B compared with group C and D (P < 0.05). IFN-gamma mRNA level significantly decreased and IL-4 mRNA significantly increased in group A and B compared to group C and D (P < 0.05).</p><p><b>CONCLUSIONS</b>Blockade of costimulatory pathway with gene therapy of ICOSIg alleviated autoimmune inflammatory damage and improved cardiac function in Lewis rats with EAM. Down-regulated costimulatory molecules in the myocardium and reduced inflammatory cytokine secretion might be responsible for the beneficial effects of ICOSIg in this model.</p>

IL-10 gene modification on immature dendritic cells induces antigen-specific tolerance in experimental autoimmune myocarditis / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate whether IL-10 gene modification on immature dendritic cells (iDC) could induce autoimmune tolerance in rat experimental autoimmune myocarditis (EAM).</p><p><b>METHODS</b>EAM was induced by cardiac myosin immunization on day 0 and day 7 in rats. A total of 2 x 10(6) mature DC (mDC), iDC, pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or PBS were injected intravenously at 5th immunization day. Three weeks later, echocardiography and HE staining were performed to observe the cardiac function and myocardial inflammation. Th1/Th2 cytokines were detected by ELISA and MHC-II molecules, costimulatory molecules were identified by flow cytometry. In vitro T lymphocyte proliferation assay and adoptive transfer of DCs were performed to determine the antigen specific tolerance induced by IL-10 gene modification on iDCs.</p><p><b>RESULTS</b>EAM rats treated with pcDNA3-IL-10 transfected iDC showed improved cardiac function and reduced inflammatory cells infiltration into myocardium. Moreover, lower Th1 and higher Th2-type response was induced, MHC-II and costimulatory molecules down-regulated and antigen specific immunological responses towards cardiac myosin inhibited in pcDNA3-IL-10-iDC treated EAM rats.</p><p><b>CONCLUSION</b>Treatment with IL-10 gene modified iDCs could ameliorates EAM by inducing Th2 polarization and down-regulation of MHC-II molecules and costimulatory molecule expressions.</p>

Antigen-specific tolerance induced by IL-10 gene modified immature dendritic cells in experimental autoimmune myocarditis in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Experimental autoimmune myocarditis (EAM) in rats is a T-cell-mediated disorder. The initiation and maintenance of autoimmune responses in EAM depend on the maturation state of dendritic cells. IL-10 is a pleiotrophic immunomodulatory cytokine that functions at different levels of the immune response, so it has emerged as a promising therapeutic factor for the treatment of autoimmune/inflammatory diseases. This study was designed to test the hypothesis that IL-10 gene modified bone marrow-derived immature dendritic cells (iDCs) ameliorate EAM and to explore the underlying mechanisms.</p><p><b>METHODS</b>EAM was induced using the methods of cardiac myosin immunization on day 0 and day 7. Immature and mature bone marrow-derived dendritic cells (BMDCs) were generated without or with the stimulation by lipopolysaccharide (LPS) and the phenotype was analyzed by flow cytometry. Some of the iDCs were transfected by pcDNA3-IL-10 plasmid. 2 x 10(6)/per rat mature DC (mDC), immature DC (iDC), pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or phosphate buffered saline (PBS) were injected intravenously for treatment 5 days after the first immunization. On day 21, HE staining was performed to detect the myocardial inflammation and T lymphocyte proliferation assay was used to determine the effects of IL-10 gene transfected iDC on autoreactive T cell proliferation. Expression of IkappaB, the inhibitor of NF-kappaB pathway, was determined by Western blot.</p><p><b>RESULTS</b>BMDCs generated in a medium supplemented with granulocyte-macrophage-colony-stimulating factor (GM-CSF) were relatively immature, as determined by flow cytometry. However, stimulation with LPS induced these cells to become mature (m) DCs with higher levels of surface major histocompatibility complex (MHC)-II and costimulatory molecules. Intravenous administration of iDCs, especially pcDNA3-IL-10 transfected iDC, ameliorated the histopathological severity of the myosin induced-EAM, and the effect was lost after the DCs underwent maturation induced by in vitro exposure to LPS. IL-10 gene modified iDC inhibited the antigen specific T cell responses towards cardiac myosin. IkappaB protein was up-regulated significantly in the IL-10 gene modified iDC group.</p><p><b>CONCLUSIONS</b>IL-10 gene modified iDC induced antigen-specific tolerance in EAM. The underlying mechanisms may be related to costimulatory molecules down-regulation and NF-kappaB pathway inhibition.</p>

The study of abnormal glucose and short term prognosis of emergency percutaneous coronary intervention for acute myocardial infarction / 中国基层医药

Objective To investigate the recent prognosis of stress hyperglycemia for the emergency percuta- neous coronary intervention(PCI)with ST-segment elevation acute myocardial infarction(AMI).Methods 410 pa- tients treated by emergency PCI were chosen.According to a history of diabetes and blood glucose levels,they were randomly divided into four groups:group 1(n = 288):random blood glucose normal and non-diabetic patients;group 2(n = 30):random normal blood glucose in diabetic patients;group 3(n = 54):random plasma glucose level and non- diabetic patients;group 4(n = 38):high random plasma glucose level in diabetic patients.Age,gender,hospital within 24 hours with random glucose,glycated hemoglobin(HbA1c),peak creatine kinase,TIMI flow recovery and 30-day mortality of the patients were compared.Results Mortality of four groups were 4.2%,3.4%,7.5% and 5.9% re- spectively(P

Study on intelligent trans-femoral prosthesis with terrain identification / 中国康复理论与实践

@#ObjectiveTo investigate the necessary of letting the intelligent knee joint be adaptive to the road terrain and the key technology of knee moment control method. MethodsBased on data from gait analysis and the dynamic model of lower limb,the knee moments while people walking on the path of different terrain were obtained. Terrain identification method was based on the features of electromyography(EMG) signals of the thigh,and the EMG of some muscles was detected. The methods were applied to an intelligent trans-femoral prosthesis developed for tests in the laboratory.ResultsConsiderable variation of the knee moments appeared when people walking on the path of different terrain,as well as that of the features of EMG of some muscles.ConclusionIt is necessary to make the intelligent knee joint be adaptive to the road terrain,and it is possible to be achieved with satisfied motion of the leg and the trajectory of ankle joint by the intelligent transfemoral prosthesis being studied which can identify the features of EMG signals.