Objective To observe the spatial and temporal distribution of collagen in fetal and adult rats wounds. Methods The organization of collagen deposition in fetal and adult rats skin wounds were observed by using van Gie...Objective To observe the spatial and temporal distribution of collagen in fetal and adult rats wounds. Methods The organization of collagen deposition in fetal and adult rats skin wounds were observed by using van Gieson stain. The methods of immunohistochemistry and in situ hybridization were applied to examine collagen type Ⅰ and Ⅲ peptide and mRNA localization at serial time point during wound healing. Results Collagen type Ⅰ and Ⅲ were present in wounds of both fetal and adult rats, but the timing and pattern of collagen deposition varied. In the fetus, collagen wes detected by 48h postwounding (PW), but uns not present in the adult wounds until 5d PW. N in situ hybridization, signals in the area of the fetal wound were clearly greater and with increased number of cells as compered to that in the adjacent unwounded tissue. Adult rat wounds had evidence in increased signals of procollagen type Ⅰ and Ⅲ production by wound fibroblasts on day 5. Collagen deposited and wes arranged in reticular pattern as that of the nounal in fetal wounds. While in the adult wound, collagen deposited in the fashion of course bundles. bundles Conclusion Fetal rat wounds appeared to produce collagen mainly by an increased number offibroblasts in the area of the wound. In contrast, adult rat wounds underwent fibroblast migration and induction of procollagen mRNA synthesis. Our results Suggest that the deposition of collagen type Ⅰ and Ⅲ is regulated by their gene expression. Chllagen type Ⅲ plays an important role in the arrangement of collagen depoition.展开更多
Significant progress has been made in designing bone materials capable of directing endogenous cells to promote vascularized bone regeneration.However,current strategies lack regulation of the specific endogenous cell...Significant progress has been made in designing bone materials capable of directing endogenous cells to promote vascularized bone regeneration.However,current strategies lack regulation of the specific endogenous cell populations for vascularized bone regeneration,thus leading to adverse tissue formation and decreased regenerative efficiency.Here,we engineered a biomaterial to regulate endogenous cell adhesion and promote vascularized bone regeneration.The biomaterial works by presenting two synthetic ligands,LLP2A and LXW7,explicitly targeting integrinsα4β1 andαvβ3,respectively,expressed on the surfaces of the cells related to bone formation and vascularization,such as mesenchymal stem cells(MSCs),osteoblasts,endothelial progenitor cells(EPCs),and endothelial cells(ECs).In vitro,the LLP2A/LXW7 modified biomaterial improved the adhesion of MSCs,osteoblasts,EPCs,and ECs via integrinα4β1 andαvβ3,respectively.In an adult rat calvarial bone defect model,the LLP2A/LXW7 modified biomaterial enhanced bone formation and vascularization by synergistically regulating endogenous cells with osteogenic and angiogenic potentials,such as DLX5^(+)cells,osteocalcin^(+)cells,CD34^(+)/CD45-cells and CD31^(+)cells.In a fetal sheep spinal bone defect model,the LLP2A/LXW7 modified biomaterial augmented bone formation and vascularization without any adverse effects.This innovative biomaterial offers an off-the-shelf,easy-to-use,and biologically safe product suitable for vascularized bone regeneration in both fetal and adult disease environments.展开更多
Objective To evaluate the frequency, distribution and clinical significance of the antibodies to the fetal and/or adult acetylcholine receptor （AChR） in patients with myasthenia gravis （MG）. Methods AChR antibodie...Objective To evaluate the frequency, distribution and clinical significance of the antibodies to the fetal and/or adult acetylcholine receptor （AChR） in patients with myasthenia gravis （MG）. Methods AChR antibodies were detected by cell-based assay in the serum of ocular MG （OMG） （n = 90） and generalized MG （GMG） patients （n = 110）. The fetal-type （2α： β： γ： δ） and adult-type （2α： β： ε： δ） AChR were used as antigens, and their relevance to disease presentation was assessed. Results The overall frequencies of anti-adult and anti-fetal AChR antibodies were similar in all 200 patients examined, with 14 having serum specific to the AChR-γ subunit, and 22 to the AChR-ε subunit. The overall sensitivity when using the fetal and adult AChR antibodies was higher than that when using the fetal AChR antibody only （P = 0.015）. Compared with OMG patients, the mean age at disease onset and the positive ratio of antibodies to both isoforms of the AChR were significantly higher in patients who subsequently progressed to GMG. Older patients and patients with both anti-fetal and anti-adult AChR antibodies had a greater risk for developing generalized disease [odds ratio （OR）, 1.03; 95% confidence interval （CI）, 1.01–1.06 and OR, 5.09; 95% CI, 2.23–11.62]. Conclusion Using both fetal-and adult-type AChRs as the antigens may be more sensitive than using either subtype. Patients with serum specific to both isoforms are at a greater risk of progressing to GMG. Patients with disease onset at an advanced age appear to have a higher frequency of GMG conversion.展开更多
文摘Objective To observe the spatial and temporal distribution of collagen in fetal and adult rats wounds. Methods The organization of collagen deposition in fetal and adult rats skin wounds were observed by using van Gieson stain. The methods of immunohistochemistry and in situ hybridization were applied to examine collagen type Ⅰ and Ⅲ peptide and mRNA localization at serial time point during wound healing. Results Collagen type Ⅰ and Ⅲ were present in wounds of both fetal and adult rats, but the timing and pattern of collagen deposition varied. In the fetus, collagen wes detected by 48h postwounding (PW), but uns not present in the adult wounds until 5d PW. N in situ hybridization, signals in the area of the fetal wound were clearly greater and with increased number of cells as compered to that in the adjacent unwounded tissue. Adult rat wounds had evidence in increased signals of procollagen type Ⅰ and Ⅲ production by wound fibroblasts on day 5. Collagen deposited and wes arranged in reticular pattern as that of the nounal in fetal wounds. While in the adult wound, collagen deposited in the fashion of course bundles. bundles Conclusion Fetal rat wounds appeared to produce collagen mainly by an increased number offibroblasts in the area of the wound. In contrast, adult rat wounds underwent fibroblast migration and induction of procollagen mRNA synthesis. Our results Suggest that the deposition of collagen type Ⅰ and Ⅲ is regulated by their gene expression. Chllagen type Ⅲ plays an important role in the arrangement of collagen depoition.
基金supported by the National Institutes of Health(NIH)grants(5R01NS100761,1R01NS115860)California Institute for Regenerative Medicine(CIRM)grants(CLIN1-11404,CLIN2-12129,TRAN3-13332)+2 种基金the Shriners Hospitals for Children Postdoctoral Fellowship(84705-NCA-19)research grants(85108-NCA-19,85135-NCA-21)Utilization of this Shared Resource was supported by the UC Davis Comprehensive Cancer Center Support Grant awarded by the National Cancer Institute(P30CA093373).
文摘Significant progress has been made in designing bone materials capable of directing endogenous cells to promote vascularized bone regeneration.However,current strategies lack regulation of the specific endogenous cell populations for vascularized bone regeneration,thus leading to adverse tissue formation and decreased regenerative efficiency.Here,we engineered a biomaterial to regulate endogenous cell adhesion and promote vascularized bone regeneration.The biomaterial works by presenting two synthetic ligands,LLP2A and LXW7,explicitly targeting integrinsα4β1 andαvβ3,respectively,expressed on the surfaces of the cells related to bone formation and vascularization,such as mesenchymal stem cells(MSCs),osteoblasts,endothelial progenitor cells(EPCs),and endothelial cells(ECs).In vitro,the LLP2A/LXW7 modified biomaterial improved the adhesion of MSCs,osteoblasts,EPCs,and ECs via integrinα4β1 andαvβ3,respectively.In an adult rat calvarial bone defect model,the LLP2A/LXW7 modified biomaterial enhanced bone formation and vascularization by synergistically regulating endogenous cells with osteogenic and angiogenic potentials,such as DLX5^(+)cells,osteocalcin^(+)cells,CD34^(+)/CD45-cells and CD31^(+)cells.In a fetal sheep spinal bone defect model,the LLP2A/LXW7 modified biomaterial augmented bone formation and vascularization without any adverse effects.This innovative biomaterial offers an off-the-shelf,easy-to-use,and biologically safe product suitable for vascularized bone regeneration in both fetal and adult disease environments.
基金supported by the National Natural Science Foundation of China (31170864 and 81171183)
文摘Objective To evaluate the frequency, distribution and clinical significance of the antibodies to the fetal and/or adult acetylcholine receptor （AChR） in patients with myasthenia gravis （MG）. Methods AChR antibodies were detected by cell-based assay in the serum of ocular MG （OMG） （n = 90） and generalized MG （GMG） patients （n = 110）. The fetal-type （2α： β： γ： δ） and adult-type （2α： β： ε： δ） AChR were used as antigens, and their relevance to disease presentation was assessed. Results The overall frequencies of anti-adult and anti-fetal AChR antibodies were similar in all 200 patients examined, with 14 having serum specific to the AChR-γ subunit, and 22 to the AChR-ε subunit. The overall sensitivity when using the fetal and adult AChR antibodies was higher than that when using the fetal AChR antibody only （P = 0.015）. Compared with OMG patients, the mean age at disease onset and the positive ratio of antibodies to both isoforms of the AChR were significantly higher in patients who subsequently progressed to GMG. Older patients and patients with both anti-fetal and anti-adult AChR antibodies had a greater risk for developing generalized disease [odds ratio （OR）, 1.03; 95% confidence interval （CI）, 1.01–1.06 and OR, 5.09; 95% CI, 2.23–11.62]. Conclusion Using both fetal-and adult-type AChRs as the antigens may be more sensitive than using either subtype. Patients with serum specific to both isoforms are at a greater risk of progressing to GMG. Patients with disease onset at an advanced age appear to have a higher frequency of GMG conversion.
基金supported by the fund from Ministry of Education of China(20070023087)973 project of the Ministry of Science and Technology of China(2011CB964800)+1 种基金National Natural Science Foundation of China(30900557)Tianjin Research Program of Application Foundation and Advanced Technology(09JCYBJC09700)
基金supported by the Funding Project for Academic Human Resources Development in Institutions of Higher Learning under the Jurisdiction of Beijing Municipality(No.10850302)Natural Science Foundation of Shanxi Province,China(No.30900584)
