This study aimed to elucidate the potential mechanisms through which bone marrow-derived mesenchymal stem cells(BM-MSCs)may be effective in alleviating experimental colitis induced by treatment with 2,4,6-trinitrobenz...This study aimed to elucidate the potential mechanisms through which bone marrow-derived mesenchymal stem cells(BM-MSCs)may be effective in alleviating experimental colitis induced by treatment with 2,4,6-trinitrobenzene-sulfonate acid(TNBS),specifically through autophagy modulation.Methods:BM-MSCs were collected from BALB/c mice for subsequent experiments.The study employed cell counting kits(CCK-8)to investigate the impact of the MSC-conditioned medium(M medium)on the proliferation of RAW264.7 macrophages.The GFP-mRFP-LC3 adenovirus was transfected into RAW264.7 to detect autophagic flux.The gene expression of cytokines was assessed through quantitative reverse transcription polymerase chain reaction(qRT-PCR).Western blot analysis was employed to determine the presence of a binding interaction between NOD-like receptor protein 3(NLRP3)and autophagy.Furthermore,a colitis mouse model was established by TNBS induction.Clinical disease activity score was assessed regularly,and histological and morphometric analyses were performed on colonic tissues.Inflammatory serum cytokines were identified using an enzyme-linked immunosorbent assay.Results:BM-MSCs significantly promoted the proliferation of RAW264.7.In vitro lipopolysaccharide(LPS)-stimulated RAW264.7 cells,treated with BM-MSCs,triggered autophagy and inhibited cytokine mRNA expression.Additionally,in LPS-induced RAW264.7,BM-MSCs enhanced the Beclin1 protein expression and the microtubule-associated protein 1 light chain 3(LC3)-II to LC3-I ratio while suppressing the protein levels of NLRP3 and apoptosis-associated speck-like protein(ASC).Nevertheless,3-methyladenine(3-MA),an inhibitor of autophagy,prevented the impact of BM-MSCs by reducing the levels of NLRP3 and ASC proteins,suggesting that autophagy triggered the inhibition of the NLRP3 inflammasome.In comparison to the mice in the TNBS group,the mice in the TNBS+MSC group displayed a more acute form of colitis,and the IL1βand IL18 cytokines in their serum were lowered as well.In the meantime,3-MA raised IL1βand IL18 cytokine levels and worsened TNBS-induced experimental colitis.Conclusions:BM-MSCs can suppress inflammation in TNBS-induced experimental mice by inhibiting the NLRP3 inflammasome,thereby enhancing autophagy.展开更多
The Qinghai-Tibet Plateau(QTP)possesses the largest areas of permafrost in the midand low latitude regions on the earth and many large lakes in the permafrost area.Based on a comprehensive investigation around certain...The Qinghai-Tibet Plateau(QTP)possesses the largest areas of permafrost in the midand low latitude regions on the earth and many large lakes in the permafrost area.Based on a comprehensive investigation around certain typical lakes,this study found that although the presence of lakes formed different ranges of unfrozen zones in permafrost,the heating effect of lake water on surrounding permafrost is limited to a small extent.The temperature of permafrost around the lake is closely related to the distance to the lake and the ice content of the permafrost.Around lakes are ice-rich permafrost zones and permafrost temperature in this area is significantly lower than that far away from the lake,which indicates that the existence of lakes in the QTP has special effect on the permafrost distribution.Based on the monitoring results,this study presents the typical distribution pattern of the permafrost around large lakes and discusses the reasons for the distribution pattern.Due to the huge area of lakes and the significant impact of lakes on permafrost distribution,it is suggested to re-estimate the total permafrost area and underground ice storage in the QTP.展开更多
文摘This study aimed to elucidate the potential mechanisms through which bone marrow-derived mesenchymal stem cells(BM-MSCs)may be effective in alleviating experimental colitis induced by treatment with 2,4,6-trinitrobenzene-sulfonate acid(TNBS),specifically through autophagy modulation.Methods:BM-MSCs were collected from BALB/c mice for subsequent experiments.The study employed cell counting kits(CCK-8)to investigate the impact of the MSC-conditioned medium(M medium)on the proliferation of RAW264.7 macrophages.The GFP-mRFP-LC3 adenovirus was transfected into RAW264.7 to detect autophagic flux.The gene expression of cytokines was assessed through quantitative reverse transcription polymerase chain reaction(qRT-PCR).Western blot analysis was employed to determine the presence of a binding interaction between NOD-like receptor protein 3(NLRP3)and autophagy.Furthermore,a colitis mouse model was established by TNBS induction.Clinical disease activity score was assessed regularly,and histological and morphometric analyses were performed on colonic tissues.Inflammatory serum cytokines were identified using an enzyme-linked immunosorbent assay.Results:BM-MSCs significantly promoted the proliferation of RAW264.7.In vitro lipopolysaccharide(LPS)-stimulated RAW264.7 cells,treated with BM-MSCs,triggered autophagy and inhibited cytokine mRNA expression.Additionally,in LPS-induced RAW264.7,BM-MSCs enhanced the Beclin1 protein expression and the microtubule-associated protein 1 light chain 3(LC3)-II to LC3-I ratio while suppressing the protein levels of NLRP3 and apoptosis-associated speck-like protein(ASC).Nevertheless,3-methyladenine(3-MA),an inhibitor of autophagy,prevented the impact of BM-MSCs by reducing the levels of NLRP3 and ASC proteins,suggesting that autophagy triggered the inhibition of the NLRP3 inflammasome.In comparison to the mice in the TNBS group,the mice in the TNBS+MSC group displayed a more acute form of colitis,and the IL1βand IL18 cytokines in their serum were lowered as well.In the meantime,3-MA raised IL1βand IL18 cytokine levels and worsened TNBS-induced experimental colitis.Conclusions:BM-MSCs can suppress inflammation in TNBS-induced experimental mice by inhibiting the NLRP3 inflammasome,thereby enhancing autophagy.
基金supported by the Strategic Priority Research Program of Chinese Academy of Sciences(XDA23060703)the National Natural Science Foundation of China(41671068)the State Key Laboratory of Cryospheric Science(SKLCS-ZZ-2023)。
文摘The Qinghai-Tibet Plateau(QTP)possesses the largest areas of permafrost in the midand low latitude regions on the earth and many large lakes in the permafrost area.Based on a comprehensive investigation around certain typical lakes,this study found that although the presence of lakes formed different ranges of unfrozen zones in permafrost,the heating effect of lake water on surrounding permafrost is limited to a small extent.The temperature of permafrost around the lake is closely related to the distance to the lake and the ice content of the permafrost.Around lakes are ice-rich permafrost zones and permafrost temperature in this area is significantly lower than that far away from the lake,which indicates that the existence of lakes in the QTP has special effect on the permafrost distribution.Based on the monitoring results,this study presents the typical distribution pattern of the permafrost around large lakes and discusses the reasons for the distribution pattern.Due to the huge area of lakes and the significant impact of lakes on permafrost distribution,it is suggested to re-estimate the total permafrost area and underground ice storage in the QTP.
