Objective: To investigate the effect of Astragalus Injection on the Skin Lesion Degree and Caspase-14, SOCS1 and STAT3 Levels of Psoriasis Model in Balb/c Nude Mice. Methods:Sixty Balb/c nude mice were randomly divide...Objective: To investigate the effect of Astragalus Injection on the Skin Lesion Degree and Caspase-14, SOCS1 and STAT3 Levels of Psoriasis Model in Balb/c Nude Mice. Methods:Sixty Balb/c nude mice were randomly divided into groups A, B and C with 20 mice in each group. Group A mice were used as blank control, group B mice as model group and group C mice as treatment group. The PASI score of psoriasis, skin thickness, inflammatory factors, serum levels of Caspase-14, SOCS1 and STAT3 in three groups of mice were analyzed after 2 weeks of treatment. Result: After treatment, the P ASI score of group B was significantly higher than that of group C, with statistical significance (P < 0.05);there was statistical significance in the measurements of lesion skin of three groups of mice after treatment (P <0.05). Compared with the blank control group, the thickness of lesion skin in group B and C was significantly higher, and the thickness of lesion skin in treatment group was significantly lower than that in control group (P < 0.05). Compared with the blank control group, the inflammatory factors IL-17, IL-22 and IL-23 in the B and C groups were significantly increased, and the inflammatory factors IL-17, IL-22 and IL-23 in the treatment group were significantly lower than those in the model group. The levels of serum C aspase-14, SOCS1 and STAT3 in three groups of mice were significantly different after treatment (P < 0.05). Compared with the blank control group, the levels of serum C aspase-14 and SOCS1 in B and C groups were significantly lower and the levels of STAT3 were significantly higher, and the levels of inflammatory factors aspase-14 and SO in treatment group were significantly higher than those in control group. The level of CS1 was significantly lower than that of model group, and the level of STAT3 was significantly higher than that of model group (P <0.05). Conclusion: Astragalus membranaceus injection can effectively improve the degree of psoriasis in Balb/c nude mice. Its possible mechanism is that it can decrease the expression of Caspase-14 and SOCS1, reduce the degree of keratosis in the lesion site of mice, improve the local surface hyperplasia, increase the level of STAT3 and enhance the level of local cell proliferation, which is of positive significance for the rehabilitation of psoriasis.展开更多
Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and af...Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.展开更多
Cardiac fibroblast(CF)differentiation into myofibroblasts is a crucial cause of cardiac fibrosis,which increases in the extracellular matrix(ECM)stiffness.The increased stiffness further promotes CF differentiation an...Cardiac fibroblast(CF)differentiation into myofibroblasts is a crucial cause of cardiac fibrosis,which increases in the extracellular matrix(ECM)stiffness.The increased stiffness further promotes CF differentiation and fibrosis.However,the molecular mechanism is still unclear.We used bioinformatics analysis to find new candidates that regulate the genes involved in stiffnessinduced CF differentiation,and found that there were binding sites for the POU-domain transcription factor,POU2F1(also known as Oct-1),in the promoters of 50 differentially expressed genes(DEGs)in CFs on the stiffer substrate.Immunofluorescent staining and Western blotting revealed that pathological stiffness upregulated POU2F1 expression and increased CF differentiation on polyacrylamide hydrogel substrates and in mouse myocardial infarction tissue.A chromatin immunoprecipitation assay showed that POU2F1 bound to the promoters of fibrosis repressors IL1R2,CD69,and TGIF2.The expression of these fibrosis repressors was inhibited on pathological substrate stiffness.Knockdown of POU2F1 upregulated these repressors and attenuated CF differentiation on pathological substrate stiffness(35 kPa).Whereas,overexpression of POU2F1 downregulated these repressors and enhanced CF differentiation.In conclusion,pathological stiffness upregulates the transcription factor POU2F1 to promote CF differentiation by inhibiting fibrosis repressors.Our work elucidated the crosstalk between CF differentiation and the ECM and provided a potential target for cardiac fibrosis treatment.展开更多
文摘Objective: To investigate the effect of Astragalus Injection on the Skin Lesion Degree and Caspase-14, SOCS1 and STAT3 Levels of Psoriasis Model in Balb/c Nude Mice. Methods:Sixty Balb/c nude mice were randomly divided into groups A, B and C with 20 mice in each group. Group A mice were used as blank control, group B mice as model group and group C mice as treatment group. The PASI score of psoriasis, skin thickness, inflammatory factors, serum levels of Caspase-14, SOCS1 and STAT3 in three groups of mice were analyzed after 2 weeks of treatment. Result: After treatment, the P ASI score of group B was significantly higher than that of group C, with statistical significance (P < 0.05);there was statistical significance in the measurements of lesion skin of three groups of mice after treatment (P <0.05). Compared with the blank control group, the thickness of lesion skin in group B and C was significantly higher, and the thickness of lesion skin in treatment group was significantly lower than that in control group (P < 0.05). Compared with the blank control group, the inflammatory factors IL-17, IL-22 and IL-23 in the B and C groups were significantly increased, and the inflammatory factors IL-17, IL-22 and IL-23 in the treatment group were significantly lower than those in the model group. The levels of serum C aspase-14, SOCS1 and STAT3 in three groups of mice were significantly different after treatment (P < 0.05). Compared with the blank control group, the levels of serum C aspase-14 and SOCS1 in B and C groups were significantly lower and the levels of STAT3 were significantly higher, and the levels of inflammatory factors aspase-14 and SO in treatment group were significantly higher than those in control group. The level of CS1 was significantly lower than that of model group, and the level of STAT3 was significantly higher than that of model group (P <0.05). Conclusion: Astragalus membranaceus injection can effectively improve the degree of psoriasis in Balb/c nude mice. Its possible mechanism is that it can decrease the expression of Caspase-14 and SOCS1, reduce the degree of keratosis in the lesion site of mice, improve the local surface hyperplasia, increase the level of STAT3 and enhance the level of local cell proliferation, which is of positive significance for the rehabilitation of psoriasis.
基金supported by American Diabetes Association,American Heart Association,NIH NIEHS,NIH NIA,NIH NINDS,and NIH ARRA
文摘Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.
基金support of a grant from the National Natural Science Foundation of China(81530009 to Y.Y.Z.)a grant from the National Natural Science Foundation of China(81822003 and 81670205 to H.X.)a grant from Natural Science Foundation of Beijing Municipality(7191013 to E.D.D.).
文摘Cardiac fibroblast(CF)differentiation into myofibroblasts is a crucial cause of cardiac fibrosis,which increases in the extracellular matrix(ECM)stiffness.The increased stiffness further promotes CF differentiation and fibrosis.However,the molecular mechanism is still unclear.We used bioinformatics analysis to find new candidates that regulate the genes involved in stiffnessinduced CF differentiation,and found that there were binding sites for the POU-domain transcription factor,POU2F1(also known as Oct-1),in the promoters of 50 differentially expressed genes(DEGs)in CFs on the stiffer substrate.Immunofluorescent staining and Western blotting revealed that pathological stiffness upregulated POU2F1 expression and increased CF differentiation on polyacrylamide hydrogel substrates and in mouse myocardial infarction tissue.A chromatin immunoprecipitation assay showed that POU2F1 bound to the promoters of fibrosis repressors IL1R2,CD69,and TGIF2.The expression of these fibrosis repressors was inhibited on pathological substrate stiffness.Knockdown of POU2F1 upregulated these repressors and attenuated CF differentiation on pathological substrate stiffness(35 kPa).Whereas,overexpression of POU2F1 downregulated these repressors and enhanced CF differentiation.In conclusion,pathological stiffness upregulates the transcription factor POU2F1 to promote CF differentiation by inhibiting fibrosis repressors.Our work elucidated the crosstalk between CF differentiation and the ECM and provided a potential target for cardiac fibrosis treatment.
