Susceptibility to pathogens in the elderly is heightened with age,largely because of immunosenescence.As an immune regulatory organ,bone marrow creates immune cells that move to other organs and tis-sues through the b...Susceptibility to pathogens in the elderly is heightened with age,largely because of immunosenescence.As an immune regulatory organ,bone marrow creates immune cells that move to other organs and tis-sues through the blood.Despite the significance of this process of this organ,there is limited research on changes in immune cell generation in the bone marrow and their effects on immunosenescence.In this study,the compositions of immune cells in bone marrow from young(three months)and old(24+months)mice were compared by means of mass cytometry,with further validation obtained through the reanalysis of single-cell RNA sequencing data and cell sorting via flow cytometry.The effects of differential immune cells on immunosenescence in old mice were evaluated using the Clostridium difficile(C.difficile)infection model.Our results showed that aged mice presented with a reduction in bone tra-beculae structure,which was accompanied by a notable increase in polymorphonuclear(PMN)-myeloid-derived suppressor cell(MDSC)abundance.Through bulk-seq and reverse transcription quantitative polymerase chain reaction(RT-qPCR)analysis,we identified differential genes associated with the immune response—specifically,the Th17 cell differentiation pathway.Furthermore,the increase in exported PMN-MDSCs to the large intestine resulted in increased gut permeability and inflammatory damage to the colon following C.difficile infection.After clearing the PMN-MDSCs in old mice using the anti-Gr-1 antibody,the symptoms induced by C.difficile were significantly relieved,as evidenced by an inhibited IL-17 pathway in the colon and reduced gut permeability.In conclusion,aging increases the number of PMN-MDSCs in both the generated bone marrow and the outputted intestine,which con-tributes to susceptibility to C.difficile infection.This study provides a novel target for anti-aging therapy for immunosenescence,which is beneficial for improving immune function in elders.展开更多
This study investigated the DPP-IV inhibitory activity of taste-modulating peptides from porcine bone and elucidated their inhibitory mechanisms.Sensory evaluation identified seven peptides with effects on umami taste...This study investigated the DPP-IV inhibitory activity of taste-modulating peptides from porcine bone and elucidated their inhibitory mechanisms.Sensory evaluation identified seven peptides with effects on umami taste or saltiness enhancement.Computational tools predicted that they all possessed DPP-IV inhibitory potential.Post-digestion,GPTAANRM,GPGCKAGL,NLRDNYRF and GVNAMLRK exhibited superior DPP-IV inhibition(IC_(50):206.16-317.59μmol/L).Molecular docking revealed that all these four peptides interacted with active residues in S1,S2 and S3 pocket of DPP-IV and the Lineweaver-Burk plots indicated their competitive inhibition mechanism.All these peptides alleviated insulin resistance in HepG2 cells to some extent,with GPTAANRM and GPGCKAGL notably reducing the blood glucose curve area in C57BL/6 J mice.This research enhances our understanding of the beneficial role of taste-modulating peptides in diabetes management and suggests their potential in developing dietary strategies to optimize glycemic control in diabetic individuals.展开更多
基金supported by the National Key Research and Development Program of China(2022YFF1100504)the 111 project from the Education Ministry of China(B18053)+2 种基金the National Natural Science Foundation of China(32101938 and 32302758)the China Postdoctoral Science Foundation(2022M723422)the Postdoctoral Fellowship Program of CPSF(GZB20230848).
文摘Susceptibility to pathogens in the elderly is heightened with age,largely because of immunosenescence.As an immune regulatory organ,bone marrow creates immune cells that move to other organs and tis-sues through the blood.Despite the significance of this process of this organ,there is limited research on changes in immune cell generation in the bone marrow and their effects on immunosenescence.In this study,the compositions of immune cells in bone marrow from young(three months)and old(24+months)mice were compared by means of mass cytometry,with further validation obtained through the reanalysis of single-cell RNA sequencing data and cell sorting via flow cytometry.The effects of differential immune cells on immunosenescence in old mice were evaluated using the Clostridium difficile(C.difficile)infection model.Our results showed that aged mice presented with a reduction in bone tra-beculae structure,which was accompanied by a notable increase in polymorphonuclear(PMN)-myeloid-derived suppressor cell(MDSC)abundance.Through bulk-seq and reverse transcription quantitative polymerase chain reaction(RT-qPCR)analysis,we identified differential genes associated with the immune response—specifically,the Th17 cell differentiation pathway.Furthermore,the increase in exported PMN-MDSCs to the large intestine resulted in increased gut permeability and inflammatory damage to the colon following C.difficile infection.After clearing the PMN-MDSCs in old mice using the anti-Gr-1 antibody,the symptoms induced by C.difficile were significantly relieved,as evidenced by an inhibited IL-17 pathway in the colon and reduced gut permeability.In conclusion,aging increases the number of PMN-MDSCs in both the generated bone marrow and the outputted intestine,which con-tributes to susceptibility to C.difficile infection.This study provides a novel target for anti-aging therapy for immunosenescence,which is beneficial for improving immune function in elders.
基金supported by the National Natural Science Foundation of China(Nos.32402278 and 32372463).
文摘This study investigated the DPP-IV inhibitory activity of taste-modulating peptides from porcine bone and elucidated their inhibitory mechanisms.Sensory evaluation identified seven peptides with effects on umami taste or saltiness enhancement.Computational tools predicted that they all possessed DPP-IV inhibitory potential.Post-digestion,GPTAANRM,GPGCKAGL,NLRDNYRF and GVNAMLRK exhibited superior DPP-IV inhibition(IC_(50):206.16-317.59μmol/L).Molecular docking revealed that all these four peptides interacted with active residues in S1,S2 and S3 pocket of DPP-IV and the Lineweaver-Burk plots indicated their competitive inhibition mechanism.All these peptides alleviated insulin resistance in HepG2 cells to some extent,with GPTAANRM and GPGCKAGL notably reducing the blood glucose curve area in C57BL/6 J mice.This research enhances our understanding of the beneficial role of taste-modulating peptides in diabetes management and suggests their potential in developing dietary strategies to optimize glycemic control in diabetic individuals.
