Objective To evaluate the therapeutic effect of normal mouse serum on radiation pneumonitis in mice and explore the possible mechanism.Methods Mouse models of radiation pneumonitis induced by thoracic radiation exposu...Objective To evaluate the therapeutic effect of normal mouse serum on radiation pneumonitis in mice and explore the possible mechanism.Methods Mouse models of radiation pneumonitis induced by thoracic radiation exposure were given intravenous injections of 100μL normal mouse serum or normal saline immediately after the exposure followed by injections once every other day for a total of 8 injections.On the 15th day after irradiation,histopathological changes of the lungs of the mice were examined using HE staining,the levels of TNF-α,TGF-β,IL-1αand IL-6 in the lung tissue and serum were detected using ELISA,and the percentages of lymphocytes in the lung tissue were analyzed with flow cytometry.High-throughput sequencing of exosome miRNA was carried out to explore the changes in the signaling pathways.The mRNA expression levels of the immune-related genes were detected by qRT-PCR,and the protein expressions of talin-1,tensin2,FAK,vinculin,α-actinin and paxillin in the focal adhesion signaling pathway were detected with Western blotting.Results In the mouse models of radiation pneumonitis,injections of normal mouse serum significantly decreased the lung organ coefficient,lowered the levels of TNF-α,TGF-β,IL-1αand IL-6 in the serum and lung tissues,and ameliorated infiltration of CD45^(+),CD4^(+)and Treg lymphocytes in the lung tissue(all P<0.05).The expression levels of Egfr and Pik3cd genes at both the mRNA and protein levels and the protein expressions of talin-1,tensin2,FAK,vinculin,α‑actinin and paxillin were all significantly down‑regulated in the mouse models after normal mouse serum treatment.Conclusion Normal mouse serum ameliorates radiation pneumonitis in mice by inhibiting the expressions of key proteins in the Focal adhesion signaling pathway.展开更多
Chronic low back pain and dyskinesia caused by intervertebral disc degeneration(IDD)are seriously aggravated and become more prevalent with age.Current clinical treatments do not restore the biological structure and i...Chronic low back pain and dyskinesia caused by intervertebral disc degeneration(IDD)are seriously aggravated and become more prevalent with age.Current clinical treatments do not restore the biological structure and inherent function of the disc.The emergence of tissue engineering and regenerative medicine has provided new insights into the treatment of IDD.We synthesized biocompatible layered double hydroxide(LDH)nanoparticles and optimized their ion elemental compositions to promote chondrogenic differentiation of human umbilical cord mesenchymal stem cells(hUC-MSCs).The chondrogenic differentiation of LDH-treated MSCs was validated using Alcian blue staining,qPCR,and immunofluorescence analyses.LDH-pretreated hUC-MSCs were differentiated prior to transplantation into the degenerative site of a needle puncture IDD rat model.Repair and regeneration evaluated using X-ray,magnetic resonance imaging,and tissue immunostaining 4-12 weeks after transplantation showed recovery of the disc space height and integrated tissue structure.Transcriptome sequencing revealed significant regulatory roles of the extracellular matrix(ECM)and integrin receptors of focal adhesion signaling pathway in enhancing chondrogenic differentiation and thus prompting tissue regeneration.The construction of ion-specific LDH nanomaterials for in situ intervertebral disc regeneration through the focal adhesion signaling pathway provides theoretical basis for clinical transformation in IDD treatment.展开更多
Osteoporotic bone defects pose a significant challenge for bone regeneration as they exhibit impaired healing capacity and delayed healing period.To address this issue,this study introduces a hydrogel that creates a r...Osteoporotic bone defects pose a significant challenge for bone regeneration as they exhibit impaired healing capacity and delayed healing period.To address this issue,this study introduces a hydrogel that creates a rejuvenating microenvironment,thereby facilitating efficient bone repair during the initial two weeks following bone defect surgery.The hydrogel,named GelHFS,was created through host-vip polymerization of gelatin and acrylatedβ-cyclodextrin.Incorporation of the human fetal mesenchymal stem cell secretome(HFS)formed GelHFS hydrogel aimed at mimicking a rejuvenated stem cell niche.Our results demonstrated that GelHFS hydrogel promotes cell stellate spreading and osteogenic differentiation via integrinβ1-induced focal adhesion pathway.Implantation of GelHFS hydrogel in an osteoporotic bone defect rat model recruited endogenous integrinβ1-expressing cells and enhanced new bone formation and bone strength.Our findings reveal that GelHFS hydrogel provides a rejuvenating niche for endogenous MSCs and enhances bone regeneration in osteoporotic bone defect.These findings highlight the potential of GelHFS hydrogel as an effective therapeutic strategy for addressing challenging bone healing such as osteoporotic bone regeneration.展开更多
文摘Objective To evaluate the therapeutic effect of normal mouse serum on radiation pneumonitis in mice and explore the possible mechanism.Methods Mouse models of radiation pneumonitis induced by thoracic radiation exposure were given intravenous injections of 100μL normal mouse serum or normal saline immediately after the exposure followed by injections once every other day for a total of 8 injections.On the 15th day after irradiation,histopathological changes of the lungs of the mice were examined using HE staining,the levels of TNF-α,TGF-β,IL-1αand IL-6 in the lung tissue and serum were detected using ELISA,and the percentages of lymphocytes in the lung tissue were analyzed with flow cytometry.High-throughput sequencing of exosome miRNA was carried out to explore the changes in the signaling pathways.The mRNA expression levels of the immune-related genes were detected by qRT-PCR,and the protein expressions of talin-1,tensin2,FAK,vinculin,α-actinin and paxillin in the focal adhesion signaling pathway were detected with Western blotting.Results In the mouse models of radiation pneumonitis,injections of normal mouse serum significantly decreased the lung organ coefficient,lowered the levels of TNF-α,TGF-β,IL-1αand IL-6 in the serum and lung tissues,and ameliorated infiltration of CD45^(+),CD4^(+)and Treg lymphocytes in the lung tissue(all P<0.05).The expression levels of Egfr and Pik3cd genes at both the mRNA and protein levels and the protein expressions of talin-1,tensin2,FAK,vinculin,α‑actinin and paxillin were all significantly down‑regulated in the mouse models after normal mouse serum treatment.Conclusion Normal mouse serum ameliorates radiation pneumonitis in mice by inhibiting the expressions of key proteins in the Focal adhesion signaling pathway.
基金This work was financially supported by the INTERNATIONAL COOPERATION Project of National Natural Science Foundation of China(Grant No.81810001048)the National Natural Science Foundation of China(Grant Nos.81922039,81873994,31727801,82225027 and 82001308)Key Basic Research Projects of Shanghai Science and Technology Commission(Grant No.19JC141470)。
文摘Chronic low back pain and dyskinesia caused by intervertebral disc degeneration(IDD)are seriously aggravated and become more prevalent with age.Current clinical treatments do not restore the biological structure and inherent function of the disc.The emergence of tissue engineering and regenerative medicine has provided new insights into the treatment of IDD.We synthesized biocompatible layered double hydroxide(LDH)nanoparticles and optimized their ion elemental compositions to promote chondrogenic differentiation of human umbilical cord mesenchymal stem cells(hUC-MSCs).The chondrogenic differentiation of LDH-treated MSCs was validated using Alcian blue staining,qPCR,and immunofluorescence analyses.LDH-pretreated hUC-MSCs were differentiated prior to transplantation into the degenerative site of a needle puncture IDD rat model.Repair and regeneration evaluated using X-ray,magnetic resonance imaging,and tissue immunostaining 4-12 weeks after transplantation showed recovery of the disc space height and integrated tissue structure.Transcriptome sequencing revealed significant regulatory roles of the extracellular matrix(ECM)and integrin receptors of focal adhesion signaling pathway in enhancing chondrogenic differentiation and thus prompting tissue regeneration.The construction of ion-specific LDH nanomaterials for in situ intervertebral disc regeneration through the focal adhesion signaling pathway provides theoretical basis for clinical transformation in IDD treatment.
基金National Natural Science Foundation of China(82172430 and 82272505)University Grants Committee,Research Grants Council of the Hong Kong Special Administrative Region,China(14113723,14108720,14121721,14202920,N_CUHK472/22,C7030-18G,T13-402/17-N and AoE/M-402/20)+1 种基金Heath and Medical Research Fund(HMRF)Hong Kong(17180831,08190416 and 09203436)Hong Kong Innovation Technology Commission Funds(PRP/050/19FX),CUHK direct grant(2022.042).
文摘Osteoporotic bone defects pose a significant challenge for bone regeneration as they exhibit impaired healing capacity and delayed healing period.To address this issue,this study introduces a hydrogel that creates a rejuvenating microenvironment,thereby facilitating efficient bone repair during the initial two weeks following bone defect surgery.The hydrogel,named GelHFS,was created through host-vip polymerization of gelatin and acrylatedβ-cyclodextrin.Incorporation of the human fetal mesenchymal stem cell secretome(HFS)formed GelHFS hydrogel aimed at mimicking a rejuvenated stem cell niche.Our results demonstrated that GelHFS hydrogel promotes cell stellate spreading and osteogenic differentiation via integrinβ1-induced focal adhesion pathway.Implantation of GelHFS hydrogel in an osteoporotic bone defect rat model recruited endogenous integrinβ1-expressing cells and enhanced new bone formation and bone strength.Our findings reveal that GelHFS hydrogel provides a rejuvenating niche for endogenous MSCs and enhances bone regeneration in osteoporotic bone defect.These findings highlight the potential of GelHFS hydrogel as an effective therapeutic strategy for addressing challenging bone healing such as osteoporotic bone regeneration.
