Recent studies indicated that regulatory B cells(Bregs)and nuclear factor erythroid 2-related factor 2(Nrf2)antioxidant signaling pathway play important roles in the pathogenesis of chronic graft-versus-host disease(c...Recent studies indicated that regulatory B cells(Bregs)and nuclear factor erythroid 2-related factor 2(Nrf2)antioxidant signaling pathway play important roles in the pathogenesis of chronic graft-versus-host disease(cGVHD).Mangiferin(MA),a polyphenol compound,has been reported to activate Nrf2/antioxidant-responsive element(ARE)signaling pathway.This study was aimed to investigate the effects of MA on Bregs and Nrf2 antioxidant signaling in murine splenic mononuclear cells(MNCs)in vitro.Our results revealed that MA could increase the Bregs level in murine splenic MNCs.Moreover,MA up-regulated the expression of Bregs-associated immunosuppressive factor interleukin-10(IL-10)by activating the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)and extracellular signal-regulated kinase(ERK)signaling in murine splenic MNCs.Meanwhile,MA inhibited the proinflammatory cytokines IL-2 and interferon-y(INF-y)at both mRNA and protein levels.MA also enhanced the transcription and protein expression of Nrf2 and NADPH quinine oxidoreductase 1(NQOl),whereas decreased that of Kelch-like ECH-associated protein 1(Keapl)in murine splenic MNCs.Moreover,MA promoted the proliferation and inhibited the apoptosis of murine splenic MNCs.These results suggested that MA exerts immunosuppressive effects by upregulating the Bregs level,activating the Nrf2 antioxidant pathway,and inhibiting the expression of pro-immunoinflammatory factors.MA,as a natural immunomodulatory and anti-inflammatory agent,may have a potential role in the prophylaxis and treatment of cGVHD.展开更多
Background:Allogeneic stem-cell transplantation (SCT) is a well-established immunotherapeutic strategy for multiple myeloma (MM) with a potent and often sustained graft-vs.-myeloma effect.This multicenter investigatio...Background:Allogeneic stem-cell transplantation (SCT) is a well-established immunotherapeutic strategy for multiple myeloma (MM) with a potent and often sustained graft-vs.-myeloma effect.This multicenter investigation aimed to analyze the complications and survival of haploidentical SCT in patients with MM,and compare the main outcomes with matched-related donors (MRDs).Methods:Haploidentical and MRD SCT was identified from a cohort of 97 patients with MM who received a myeloablative transplantation in 13 hospitals from May 2001 to December 2017.A matched-pair analysis was designed.For each haplo recipient,the recipients were randomly selected from the MRD group and were matched according to the following criteria:year of the hematopoietic SCT (±2 years),disease status at transplantation,and the length of follow-up.ults:Seventy cases received MRD and 27 received haploidendcal transplantation.The two groups showed no significant ifferences regarding age,gender,cytogenetic risk,and diagnostic stage.The cumulative incidences of non-relapse mortality (NRM) at1 and 3 years based on donor type were 20.5%(95% confidence interval [CI],10.90-30.10%) and 24.2%(95% CI,13.81-34.59%) for the MRD group and 16.80%(95% CI,1.71-31.89%) and 28.70%(95% CI,8.71-48.69%) for the haplo group,respectively.Cumulative incidence of NRM did not differ significantly between the two groups (x2 =0.031,P =0.861).The cumulative incidences of progression-free survival (PFS) and 1 year and 3 years by type of donors were 59.8 %(95 % CI,48.24-71.36 %) and 45.4 %(95 % CI,33.44-57.36%),and 65.6%(95% CI,47.18-84.02%) and 26.8%(95% CI,7.59-46.01%) for MRD and haploidentical donor,respectively.Cumulative incidence of PFS did not differ significantly between the two groups (x2 =0.182,P =0.670).In multivariate analyses,no statistically significant differences were observed between haploidentical and MRD for relapse,NRM,PFS,and overall survival.There were no statistically differences on main outcomes after haploidentical and MRD.Conclusion:Haploidentical SCT could be performed safely and feasibly for patients with MM in need.展开更多
基金the National Natural Science Foundation of China(No.81470347,No.81974003)The authors would like to thank the Department of Central Laboratory,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China,for providing relevant experimental facilities and technical support.
文摘Recent studies indicated that regulatory B cells(Bregs)and nuclear factor erythroid 2-related factor 2(Nrf2)antioxidant signaling pathway play important roles in the pathogenesis of chronic graft-versus-host disease(cGVHD).Mangiferin(MA),a polyphenol compound,has been reported to activate Nrf2/antioxidant-responsive element(ARE)signaling pathway.This study was aimed to investigate the effects of MA on Bregs and Nrf2 antioxidant signaling in murine splenic mononuclear cells(MNCs)in vitro.Our results revealed that MA could increase the Bregs level in murine splenic MNCs.Moreover,MA up-regulated the expression of Bregs-associated immunosuppressive factor interleukin-10(IL-10)by activating the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)and extracellular signal-regulated kinase(ERK)signaling in murine splenic MNCs.Meanwhile,MA inhibited the proinflammatory cytokines IL-2 and interferon-y(INF-y)at both mRNA and protein levels.MA also enhanced the transcription and protein expression of Nrf2 and NADPH quinine oxidoreductase 1(NQOl),whereas decreased that of Kelch-like ECH-associated protein 1(Keapl)in murine splenic MNCs.Moreover,MA promoted the proliferation and inhibited the apoptosis of murine splenic MNCs.These results suggested that MA exerts immunosuppressive effects by upregulating the Bregs level,activating the Nrf2 antioxidant pathway,and inhibiting the expression of pro-immunoinflammatory factors.MA,as a natural immunomodulatory and anti-inflammatory agent,may have a potential role in the prophylaxis and treatment of cGVHD.
基金supported by the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(81621001)the National Natural Science Foundation of China(82100227)+1 种基金the Key Program of National Natural Science Foundation of China(81930004)the National Key Research and Development Program of China(2017YFA0104500)。
基金grants from Foundation for Innovative Research Groups of the National Natural Science Foundation of China (No. 81621001)National Natural Science Foundation of China (Nos. 81670167 and 81670166).
文摘Background:Allogeneic stem-cell transplantation (SCT) is a well-established immunotherapeutic strategy for multiple myeloma (MM) with a potent and often sustained graft-vs.-myeloma effect.This multicenter investigation aimed to analyze the complications and survival of haploidentical SCT in patients with MM,and compare the main outcomes with matched-related donors (MRDs).Methods:Haploidentical and MRD SCT was identified from a cohort of 97 patients with MM who received a myeloablative transplantation in 13 hospitals from May 2001 to December 2017.A matched-pair analysis was designed.For each haplo recipient,the recipients were randomly selected from the MRD group and were matched according to the following criteria:year of the hematopoietic SCT (±2 years),disease status at transplantation,and the length of follow-up.ults:Seventy cases received MRD and 27 received haploidendcal transplantation.The two groups showed no significant ifferences regarding age,gender,cytogenetic risk,and diagnostic stage.The cumulative incidences of non-relapse mortality (NRM) at1 and 3 years based on donor type were 20.5%(95% confidence interval [CI],10.90-30.10%) and 24.2%(95% CI,13.81-34.59%) for the MRD group and 16.80%(95% CI,1.71-31.89%) and 28.70%(95% CI,8.71-48.69%) for the haplo group,respectively.Cumulative incidence of NRM did not differ significantly between the two groups (x2 =0.031,P =0.861).The cumulative incidences of progression-free survival (PFS) and 1 year and 3 years by type of donors were 59.8 %(95 % CI,48.24-71.36 %) and 45.4 %(95 % CI,33.44-57.36%),and 65.6%(95% CI,47.18-84.02%) and 26.8%(95% CI,7.59-46.01%) for MRD and haploidentical donor,respectively.Cumulative incidence of PFS did not differ significantly between the two groups (x2 =0.182,P =0.670).In multivariate analyses,no statistically significant differences were observed between haploidentical and MRD for relapse,NRM,PFS,and overall survival.There were no statistically differences on main outcomes after haploidentical and MRD.Conclusion:Haploidentical SCT could be performed safely and feasibly for patients with MM in need.
