The purpose of this study was to investigate the repair of the osteoarthritis（OA）-induced car- tilage injury by transfecting the new TGF-β3 fusion protein （LAP-MMP-mTGF-β3） with targeted ther- apy function into ...The purpose of this study was to investigate the repair of the osteoarthritis（OA）-induced car- tilage injury by transfecting the new TGF-β3 fusion protein （LAP-MMP-mTGF-β3） with targeted ther- apy function into the bone marrow-derived mesenchymal stem cells （MSCs） in rats. The recombinant of plRES-EGFP-MMP was constructed by combination of DNA encoding MMP enzyme cutting site and eukaryotic expression vector plRES-EGFP. LAP and mTGF-β3 fragments were obtained from rat em- bryos by RT-PCR and inserted into the upstream and downstream of MMP from plRES-EGFP-MMP respectively, so as to construct the recombinant plasmid ofplRES-EGFP-LAP-MMP-mTGF-β3, plRES- EGFP-LAP-MMP-mTGF-β3 was transfected into rat MSCs. The genetically modified MSCs were cul- tured in medium with MMP-1 or not. The transfected MSCs were transplanted in the rat OA models. The OA animal models were surgically induced by anterior cruciate ligament transaction （ACLT）. The pathological changes were observed under a microscope by HE staining, Alcian blue, Safranin-fast Gre- en and graded by Mankin＇s scale, plRES-EGFP-LAP-MMP-mTGF-β3 was successfully constructed by means of enzyme cutting and sequencing, and the mTGF-β3 fusion protein （39 kD） was certified by Western blotting. Those genetically modified MSCs could differentiate into chondrocytes induced by MMP and secrete the relevant-matrix. The transfected MSCs could promote chondrogenesis and matrix production in rat OA models in vivo. It was concluded that a new fusion protein LAP-MMP-mTGF-β3 was constructed successfully by gene engineering, and could be used to repair the OA-induced cartilage injury.展开更多
Background: It is yet a controversy subject whether low birth weight and infant death are associated to human immunodeficiency virus-1 infection. Objective: To appreciate association between low birth weights, mother ...Background: It is yet a controversy subject whether low birth weight and infant death are associated to human immunodeficiency virus-1 infection. Objective: To appreciate association between low birth weights, mother to child HIV transmission and infant mortality in HIV-1 infected pregnant women delivering between 2011 and 2016. Materials: We conducted 6 years cohort study in urban Mali. Outcome included preterm delivery, small for gestational age, infant survival status and HIV transmission. Comparison concerned women clinical WHO stage, mother viro-immunological status, and newborn anthropometric parameters. Results: HIV-1 infected women who delivered low birth weight newborn were 20.9% (111/531) versus 16.5% (1910/11.546) in HIV negative patients (p = 0.016). CD4 T cell counts low than 350 T cells count were strongly associated to LBW (p = 0.000;RR = 3.03;95% CI [1.89 - 3.16]). There is no significant association between ART that was initiated during pregnancy (p = 0.061, RR = 0.02;CI 95% (1.02 - 1.99)) or during delivery (p = 0.571;RR = 1.01;CI 95% (0.10 - 3.02)) and LBW delivery. In multivariate analysis ART regimens containing protease inhibitor (PI) were lone regimens associated with LBW ((p = 0.030;RR = 1.001;95% confidence interval [1.28 - 3.80]). Very low birth weight was statistically associated to women HIV infection (adjusted relative risk, 2.02;p = 0.000;95% confidence interval (2.17 - 4.10)). There is no significant difference between mother to child HIV transmission rate in the two HIV-infected pregnant women (10 infected children in group 2: MTCT rate 4.5%) and 3 infected children in group 1 (MTCT rate: 2.7%) (p = 0.56;RR, 0.59;CI 95% (0.18 - 4.39)). In multivariate analysis, LBW was associated with infant death (p = 0.001;RR = 2.04;CI 95% [1.04 - 5.05]). The median weight of infant at the moment of death in group 1 was 851 g (IQR: 520 - 1833 g). Significant relationship was found between infant death among LBW newborn with mother WHO stage 2 (p = 0.004;adjusted RR = 3.22;CI 95% [2.25 - 6.00]), CD4 T cells count 3 (p = 0.005;RR = 2.81;CI 95% [1.20 - 4.11]), PI regimens (p = 0.030;RR = 1.00;CI 95% [1.28 - 3.80]). Conclusion: We confirm increased risk of low birth weight and mother HIV-1 infection and we identified strongest association between mortality in infant born to HIV-1 infected mother and LBW.展开更多
基金supported by the National Natural Science Foundation of China(No.81101376)
文摘The purpose of this study was to investigate the repair of the osteoarthritis（OA）-induced car- tilage injury by transfecting the new TGF-β3 fusion protein （LAP-MMP-mTGF-β3） with targeted ther- apy function into the bone marrow-derived mesenchymal stem cells （MSCs） in rats. The recombinant of plRES-EGFP-MMP was constructed by combination of DNA encoding MMP enzyme cutting site and eukaryotic expression vector plRES-EGFP. LAP and mTGF-β3 fragments were obtained from rat em- bryos by RT-PCR and inserted into the upstream and downstream of MMP from plRES-EGFP-MMP respectively, so as to construct the recombinant plasmid ofplRES-EGFP-LAP-MMP-mTGF-β3, plRES- EGFP-LAP-MMP-mTGF-β3 was transfected into rat MSCs. The genetically modified MSCs were cul- tured in medium with MMP-1 or not. The transfected MSCs were transplanted in the rat OA models. The OA animal models were surgically induced by anterior cruciate ligament transaction （ACLT）. The pathological changes were observed under a microscope by HE staining, Alcian blue, Safranin-fast Gre- en and graded by Mankin＇s scale, plRES-EGFP-LAP-MMP-mTGF-β3 was successfully constructed by means of enzyme cutting and sequencing, and the mTGF-β3 fusion protein （39 kD） was certified by Western blotting. Those genetically modified MSCs could differentiate into chondrocytes induced by MMP and secrete the relevant-matrix. The transfected MSCs could promote chondrogenesis and matrix production in rat OA models in vivo. It was concluded that a new fusion protein LAP-MMP-mTGF-β3 was constructed successfully by gene engineering, and could be used to repair the OA-induced cartilage injury.
文摘Background: It is yet a controversy subject whether low birth weight and infant death are associated to human immunodeficiency virus-1 infection. Objective: To appreciate association between low birth weights, mother to child HIV transmission and infant mortality in HIV-1 infected pregnant women delivering between 2011 and 2016. Materials: We conducted 6 years cohort study in urban Mali. Outcome included preterm delivery, small for gestational age, infant survival status and HIV transmission. Comparison concerned women clinical WHO stage, mother viro-immunological status, and newborn anthropometric parameters. Results: HIV-1 infected women who delivered low birth weight newborn were 20.9% (111/531) versus 16.5% (1910/11.546) in HIV negative patients (p = 0.016). CD4 T cell counts low than 350 T cells count were strongly associated to LBW (p = 0.000;RR = 3.03;95% CI [1.89 - 3.16]). There is no significant association between ART that was initiated during pregnancy (p = 0.061, RR = 0.02;CI 95% (1.02 - 1.99)) or during delivery (p = 0.571;RR = 1.01;CI 95% (0.10 - 3.02)) and LBW delivery. In multivariate analysis ART regimens containing protease inhibitor (PI) were lone regimens associated with LBW ((p = 0.030;RR = 1.001;95% confidence interval [1.28 - 3.80]). Very low birth weight was statistically associated to women HIV infection (adjusted relative risk, 2.02;p = 0.000;95% confidence interval (2.17 - 4.10)). There is no significant difference between mother to child HIV transmission rate in the two HIV-infected pregnant women (10 infected children in group 2: MTCT rate 4.5%) and 3 infected children in group 1 (MTCT rate: 2.7%) (p = 0.56;RR, 0.59;CI 95% (0.18 - 4.39)). In multivariate analysis, LBW was associated with infant death (p = 0.001;RR = 2.04;CI 95% [1.04 - 5.05]). The median weight of infant at the moment of death in group 1 was 851 g (IQR: 520 - 1833 g). Significant relationship was found between infant death among LBW newborn with mother WHO stage 2 (p = 0.004;adjusted RR = 3.22;CI 95% [2.25 - 6.00]), CD4 T cells count 3 (p = 0.005;RR = 2.81;CI 95% [1.20 - 4.11]), PI regimens (p = 0.030;RR = 1.00;CI 95% [1.28 - 3.80]). Conclusion: We confirm increased risk of low birth weight and mother HIV-1 infection and we identified strongest association between mortality in infant born to HIV-1 infected mother and LBW.
