Objective:Psoriasis is associated with lipid metabolism disorders,but the underlying mechanisms remain unclear.This study aims to investigate the role of trimethylamine Noxide(TMAO)in lipid metabolism dysregulation in...Objective:Psoriasis is associated with lipid metabolism disorders,but the underlying mechanisms remain unclear.This study aims to investigate the role of trimethylamine Noxide(TMAO)in lipid metabolism dysregulation in psoriasis.Methods:An imiquimod(IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters,TMAO levels,and liver flavin monooxygenase 3(FMO3)mRNA expression.Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles.To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model,exogenous TMAO,choline,or 3,3-dimethyl-1-butanol(DMB)were administered via intraperitoneal injections or diet in IMQ-treated mice.Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways.Results:IMQ-induced psoriatic mice exhibited abnormal glucose,insulin,and lipid levels.IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2(Glut2)and silence information regulator 1(Sirt1),while upregulating glucose transporter 4(Glut4)and peroxisome proliferator-activated receptor gamma(PPARγ).Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice.Additionally,liver FMO3 mRNA expression was increased in the psoriatic mouse model.In patients,TMAO levels positively correlated with Psoriasis Area and Severity Index(PASI)scores,serum triglyceride(TG),and total cholesterol(TC)levels.The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice.A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice,whereas DMB treatment alleviated these effects.RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122(miR-122),which may suppress the expression of gremlin 2(GREM2),thus contributing to lipid metabolism disorder.Conclusion:TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.展开更多
OBJECTIVE Psoriasis is an immune system meditated disease,especially T cells.It disturbed many people around the world and hard to therapy.Paeonia lactiflora Pall has been used as a medicine in china for thousands of ...OBJECTIVE Psoriasis is an immune system meditated disease,especially T cells.It disturbed many people around the world and hard to therapy.Paeonia lactiflora Pall has been used as a medicine in china for thousands of years.Recent studies has found that the main component of Paeonia lactiflora Pall can alleviates the immune response in many diseases.In this study,we researched the effects and possible mechanisms of total glucosides of paeony(TGP)on animal psoriasis in order to study the therapeutic effects and mechanisms of TGP in 5%propranolol creaminduced psoriasis in guinea pigs and Imiquimod(IMQ)cream-induced psoriasis in mice.METHODS The effect of TGP was evaluated using a psoriasis-like model of guinea pigs and mice.Ear thickness was accessed,and pathology injury was observed by HE staining.The levels of serum IL-1β,IL-6,IL-12,IL-17,IL-23,TNF-α,and IFN-γ,skin IL-17A,IL-22 and orphan nuclear receptor(RORγt)mRNA expression,proliferating cell nuclear antigen(PCNA),total or phosphorylated signal transducers and activators of transcription(STAT1 and STAT3)were determined by ELISA,real time PCR,immu⁃nohistochemical staining,and Western blotting,respectively.RESULTS Compared with model group,TGP treatment decreased the ear thickness,improved pathology of psoriasis,alleviated IMQ-induced keratinocyte proliferation,reduced the inflammatory cytokine,and downregulated IL-17A,IL-22,and RORγt mRNA in mice.Further study indicated that TGP inhibited STAT1 and STAT3 phosphorylation in lesion skins of psoriasis-like mice.CONCLUSION TGP alleviates the symptoms of psoriasis-like guinea pigs and mice,and the possible mechanism may relate to inhibit T helper 17(TH17)cell differentiation and keratinocytes proliferation by inhibiting STAT1 and STAT3 phosphorylation.展开更多
OBJECTIVE Recently,some reports show that curcuma has a good curative effect on the treatment of psoriasis;while curcuma has many components,so the present study was designed to investigate the effective parts of curc...OBJECTIVE Recently,some reports show that curcuma has a good curative effect on the treatment of psoriasis;while curcuma has many components,so the present study was designed to investigate the effective parts of curcuma on treatment of psoriasis,in addition,we will explore the mechanisms of curcuma therapeutic effect.METHODS First,we observed that curcuma′s extractions effect on mitosis of mouse vaginal epithelial cells;then psoriasis like was induced by wiping imiquimod in the surface of the binaural dorsal skin of the animal,the score of skin damage was measured on days 7 and 14;in order to explore the mechanisms of curcuma’s extractions on psoriasis,immune factors expression(CK14,CK16,CK17,PCNA,TLR-2,TLR-4,TLR-9)was determined in propranolol induced psoriasis like.RESULTS Curcuma′s extraction prohibited the mitosis of mouse vaginal epithelial cells;curcuma’s extractions produced a significant and dose dependent inhibition of psoriasis during the entire duration of the study in imiquimod induced psoriasis like;and the expression of immune factors(CK14,CK16,CK17,PCNA,TLR-2,TLR-4,TLR-9)was also found to be less in the curcuma′s extraction treated group as compared to control.CONCLUSION We believe that the curative effectof curcuma’sextraction may due to its inhibition effect on the expression of immune factors.Our results contribute towards validation of curcuma in the treatment of psoriasis and other joint disorders.展开更多
Reversible SAHH inhibitor ameliorates psoriasis-like skin inflammation in mice by modulating keratinocyte differentiation and reducing inflammatory infiltration via differentially regulating DNA methylation of GATA3 a...Reversible SAHH inhibitor ameliorates psoriasis-like skin inflammation in mice by modulating keratinocyte differentiation and reducing inflammatory infiltration via differentially regulating DNA methylation of GATA3 and LCN2 promoters,OBJECTIVE To investigate the anti-psoriatic molecular mechanisms of DZ2002.METHODS We performed genome-wide DNA methylation analysis by whole-genome bisulfite sequencing(WGBS)to investigate Cp G methylation alteration in skin of imiquimod(IMQ)-induced psoriasis-like murine model topically treated with DZ2002.Immunohistochemical analysis and flow cytometry examination were used to detect skin infiltration of immune cells.展开更多
基金supported by the National Natural Science Foundation(82173426)the Natural Science Foundation of Hunan Province(2023JJ30984),China。
文摘Objective:Psoriasis is associated with lipid metabolism disorders,but the underlying mechanisms remain unclear.This study aims to investigate the role of trimethylamine Noxide(TMAO)in lipid metabolism dysregulation in psoriasis.Methods:An imiquimod(IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters,TMAO levels,and liver flavin monooxygenase 3(FMO3)mRNA expression.Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles.To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model,exogenous TMAO,choline,or 3,3-dimethyl-1-butanol(DMB)were administered via intraperitoneal injections or diet in IMQ-treated mice.Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways.Results:IMQ-induced psoriatic mice exhibited abnormal glucose,insulin,and lipid levels.IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2(Glut2)and silence information regulator 1(Sirt1),while upregulating glucose transporter 4(Glut4)and peroxisome proliferator-activated receptor gamma(PPARγ).Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice.Additionally,liver FMO3 mRNA expression was increased in the psoriatic mouse model.In patients,TMAO levels positively correlated with Psoriasis Area and Severity Index(PASI)scores,serum triglyceride(TG),and total cholesterol(TC)levels.The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice.A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice,whereas DMB treatment alleviated these effects.RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122(miR-122),which may suppress the expression of gremlin 2(GREM2),thus contributing to lipid metabolism disorder.Conclusion:TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.
基金China Pharmaceutical University "Double First-Class" University project(CPU2018GY32)National Science and Technology Major Project of China(2016ZX09101031)
文摘OBJECTIVE Psoriasis is an immune system meditated disease,especially T cells.It disturbed many people around the world and hard to therapy.Paeonia lactiflora Pall has been used as a medicine in china for thousands of years.Recent studies has found that the main component of Paeonia lactiflora Pall can alleviates the immune response in many diseases.In this study,we researched the effects and possible mechanisms of total glucosides of paeony(TGP)on animal psoriasis in order to study the therapeutic effects and mechanisms of TGP in 5%propranolol creaminduced psoriasis in guinea pigs and Imiquimod(IMQ)cream-induced psoriasis in mice.METHODS The effect of TGP was evaluated using a psoriasis-like model of guinea pigs and mice.Ear thickness was accessed,and pathology injury was observed by HE staining.The levels of serum IL-1β,IL-6,IL-12,IL-17,IL-23,TNF-α,and IFN-γ,skin IL-17A,IL-22 and orphan nuclear receptor(RORγt)mRNA expression,proliferating cell nuclear antigen(PCNA),total or phosphorylated signal transducers and activators of transcription(STAT1 and STAT3)were determined by ELISA,real time PCR,immu⁃nohistochemical staining,and Western blotting,respectively.RESULTS Compared with model group,TGP treatment decreased the ear thickness,improved pathology of psoriasis,alleviated IMQ-induced keratinocyte proliferation,reduced the inflammatory cytokine,and downregulated IL-17A,IL-22,and RORγt mRNA in mice.Further study indicated that TGP inhibited STAT1 and STAT3 phosphorylation in lesion skins of psoriasis-like mice.CONCLUSION TGP alleviates the symptoms of psoriasis-like guinea pigs and mice,and the possible mechanism may relate to inhibit T helper 17(TH17)cell differentiation and keratinocytes proliferation by inhibiting STAT1 and STAT3 phosphorylation.
文摘OBJECTIVE Recently,some reports show that curcuma has a good curative effect on the treatment of psoriasis;while curcuma has many components,so the present study was designed to investigate the effective parts of curcuma on treatment of psoriasis,in addition,we will explore the mechanisms of curcuma therapeutic effect.METHODS First,we observed that curcuma′s extractions effect on mitosis of mouse vaginal epithelial cells;then psoriasis like was induced by wiping imiquimod in the surface of the binaural dorsal skin of the animal,the score of skin damage was measured on days 7 and 14;in order to explore the mechanisms of curcuma’s extractions on psoriasis,immune factors expression(CK14,CK16,CK17,PCNA,TLR-2,TLR-4,TLR-9)was determined in propranolol induced psoriasis like.RESULTS Curcuma′s extraction prohibited the mitosis of mouse vaginal epithelial cells;curcuma’s extractions produced a significant and dose dependent inhibition of psoriasis during the entire duration of the study in imiquimod induced psoriasis like;and the expression of immune factors(CK14,CK16,CK17,PCNA,TLR-2,TLR-4,TLR-9)was also found to be less in the curcuma′s extraction treated group as compared to control.CONCLUSION We believe that the curative effectof curcuma’sextraction may due to its inhibition effect on the expression of immune factors.Our results contribute towards validation of curcuma in the treatment of psoriasis and other joint disorders.
文摘Reversible SAHH inhibitor ameliorates psoriasis-like skin inflammation in mice by modulating keratinocyte differentiation and reducing inflammatory infiltration via differentially regulating DNA methylation of GATA3 and LCN2 promoters,OBJECTIVE To investigate the anti-psoriatic molecular mechanisms of DZ2002.METHODS We performed genome-wide DNA methylation analysis by whole-genome bisulfite sequencing(WGBS)to investigate Cp G methylation alteration in skin of imiquimod(IMQ)-induced psoriasis-like murine model topically treated with DZ2002.Immunohistochemical analysis and flow cytometry examination were used to detect skin infiltration of immune cells.
