Background Alzheimer’s disease is a neurodegenerative disorder.Therapeutically,a transplantation of bone marrow mesenchymal stem cells(BMMSCs)can play a beneficial role in animal models of Alzheimer’s disease.Howeve...Background Alzheimer’s disease is a neurodegenerative disorder.Therapeutically,a transplantation of bone marrow mesenchymal stem cells(BMMSCs)can play a beneficial role in animal models of Alzheimer’s disease.However,the relevant mechanism remains to be fully elucidated.Main body Subsequent to the transplantation of BMMSCs,memory loss and cognitive impairment were significantly improved in animal models with Alzheimer’s disease(AD).Potential mechanisms involved neurogenesis,apoptosis,angiogenesis,inflammation,immunomodulation,etc.The above mechanisms might play different roles at certain stages.It was revealed that the transplantation of BMMSCs could alter some gene levels.Moreover,the differential expression of representative genes was responsible for neuropathological phenotypes in Alzheimer’s disease,which could be used to construct gene-specific patterns.Conclusions Multiple signal pathways involve therapeutic mechanisms by which the transplantation of BMMSCs improves cognitive and behavioral deficits in AD models.Gene expression profile can be utilized to establish statistical regression model for the evaluation of therapeutic effect.The transplantation of autologous BMMSCs maybe a prospective therapy for patients with Alzheimer’s disease.展开更多
Autophagy is a catabolic process that can degrade worn-out organelles and invading pathogens.The activation of autophagy regulates innate and adaptive immunity,playing a key role in the response to microbial invasion....Autophagy is a catabolic process that can degrade worn-out organelles and invading pathogens.The activation of autophagy regulates innate and adaptive immunity,playing a key role in the response to microbial invasion.Microbial infection may cause different consequences such as the elimination of invaders through autophagy or xenophagy,host cell death,and symbiotic relationships.Pathogens adapt to the autophagy mechanism and further relieve intracellular stress,which is conducive to host cell survival and microbial growth.The regulation of autophagy forms a complex network through which host immunity is modulated,resulting in a variety of pathophysiological manifestations.Modification of the autophagic pathway is an essential target for the development of antimicrobial drugs.展开更多
Prolonged activation of nuclear factor(NF)-кB signaling significantly contributes to the development of colorectal cancer(CRC).New therapeutic opportunities are emerging from targeting this distorted cell signaling t...Prolonged activation of nuclear factor(NF)-кB signaling significantly contributes to the development of colorectal cancer(CRC).New therapeutic opportunities are emerging from targeting this distorted cell signaling transduction.Here,we discovered the critical role of RING finger 138(RNF138)in CRC tumorigenesis through regulating the NF-кB signaling,which is independent of its Ubiquitin-E3 ligase activity involved in DNA damage response.RNF138^(−/−) mice were hyper-susceptible to the switch from colitis to aggressive malignancy,which coincided with sustained aberrant NF-кB signaling in the colonic cells.Furthermore,RNF138 suppresses the activation of NF-кB signaling pathway through preventing the translocation of NIK and IKK-Beta Binding Protein(NIBP)to the cytoplasm,which requires the ubiquitin interaction motif(UIM)domain.More importantly,we uncovered a significant correlation between poor prognosis and the downregulation of RNF138 associated with reinforced NF-кB signaling in clinical settings,raising the possibility of RNF138 dysregulation as an indicator for the therapeutic intervention targeting NF-кB signaling.Using the xenograft models built upon either RNF138-dificient CRC cells or the cells derived from the RNF138-dysregulated CRC patients,we demonstrated that the inhibition of NF-кB signaling effectively hampered tumor growth.Overall,our work defined the pathogenic role of aberrant NF-кB signaling due to RNF138 downregulation in the cascade events from the colitis switch to colonic neoplastic transformation and progression,and also highlights the possibility of targeting the NF-кB signaling in treating specific subtypes of CRC indicated by RNF138-ablation.展开更多
基金This work was supported by grants Beijing Natural Science Foundation(No.517100)National Key Research and Development Project(No.2017YFA0105200)CAMS Innovation Fund for Medical Sciences(CIFMS)(2016-I2M-2-006).
文摘Background Alzheimer’s disease is a neurodegenerative disorder.Therapeutically,a transplantation of bone marrow mesenchymal stem cells(BMMSCs)can play a beneficial role in animal models of Alzheimer’s disease.However,the relevant mechanism remains to be fully elucidated.Main body Subsequent to the transplantation of BMMSCs,memory loss and cognitive impairment were significantly improved in animal models with Alzheimer’s disease(AD).Potential mechanisms involved neurogenesis,apoptosis,angiogenesis,inflammation,immunomodulation,etc.The above mechanisms might play different roles at certain stages.It was revealed that the transplantation of BMMSCs could alter some gene levels.Moreover,the differential expression of representative genes was responsible for neuropathological phenotypes in Alzheimer’s disease,which could be used to construct gene-specific patterns.Conclusions Multiple signal pathways involve therapeutic mechanisms by which the transplantation of BMMSCs improves cognitive and behavioral deficits in AD models.Gene expression profile can be utilized to establish statistical regression model for the evaluation of therapeutic effect.The transplantation of autologous BMMSCs maybe a prospective therapy for patients with Alzheimer’s disease.
基金supported by grants from Beijing Natural Science Foundation(517100)National Key Research and Development Project(2017YFA0105200)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(CIFMS,2016-12 M-2-006).
文摘Autophagy is a catabolic process that can degrade worn-out organelles and invading pathogens.The activation of autophagy regulates innate and adaptive immunity,playing a key role in the response to microbial invasion.Microbial infection may cause different consequences such as the elimination of invaders through autophagy or xenophagy,host cell death,and symbiotic relationships.Pathogens adapt to the autophagy mechanism and further relieve intracellular stress,which is conducive to host cell survival and microbial growth.The regulation of autophagy forms a complex network through which host immunity is modulated,resulting in a variety of pathophysiological manifestations.Modification of the autophagic pathway is an essential target for the development of antimicrobial drugs.
基金supported by CAMS Innovation Fund for Medical Sciences(CIFMS,2021-I2M-1-066,2017-I2M-4-002 to H.Z.,2021-I2M-1-019 to W.S.,2021-1-I2M-014 to C.Z.L.)the National Natural Science Foundation of China(81972311,82141127 and 81672461 to H.Z.,81672472,and 31970794 to W.S.,81570780 to C.Z.L.,32000586 to K.L.)+4 种基金the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences(2019PT310026 to H.Z.)Sanming Project of Medicine in Shenzhen(SZSM202011010 to H.Z.)the National Key Research and Development Program of China(2018YFC1003500 to W.S.)the State Key Laboratory Special fund from the Ministry of Science(2060204 to W.S.)the State Key Project on Infection Diseases of China(2017ZX10201021-007-003 to H.Z.).
文摘Prolonged activation of nuclear factor(NF)-кB signaling significantly contributes to the development of colorectal cancer(CRC).New therapeutic opportunities are emerging from targeting this distorted cell signaling transduction.Here,we discovered the critical role of RING finger 138(RNF138)in CRC tumorigenesis through regulating the NF-кB signaling,which is independent of its Ubiquitin-E3 ligase activity involved in DNA damage response.RNF138^(−/−) mice were hyper-susceptible to the switch from colitis to aggressive malignancy,which coincided with sustained aberrant NF-кB signaling in the colonic cells.Furthermore,RNF138 suppresses the activation of NF-кB signaling pathway through preventing the translocation of NIK and IKK-Beta Binding Protein(NIBP)to the cytoplasm,which requires the ubiquitin interaction motif(UIM)domain.More importantly,we uncovered a significant correlation between poor prognosis and the downregulation of RNF138 associated with reinforced NF-кB signaling in clinical settings,raising the possibility of RNF138 dysregulation as an indicator for the therapeutic intervention targeting NF-кB signaling.Using the xenograft models built upon either RNF138-dificient CRC cells or the cells derived from the RNF138-dysregulated CRC patients,we demonstrated that the inhibition of NF-кB signaling effectively hampered tumor growth.Overall,our work defined the pathogenic role of aberrant NF-кB signaling due to RNF138 downregulation in the cascade events from the colitis switch to colonic neoplastic transformation and progression,and also highlights the possibility of targeting the NF-кB signaling in treating specific subtypes of CRC indicated by RNF138-ablation.