Evolution of no evidence of disease activity therapeutic goals of multiple sclerosis from new progress of nerve injury mechanisms / 中华神经科杂志

Multiple sclerosis is a severe autoimmune inflammatory disease mainly involving the central nervous system. In recent years, the exploration of the mechanism of nerve injury in multiple sclerosis has made great progress. At the same time, disease-modifying therapeutic drugs with different targets are also emerging. Understanding of the mechanisms of nerve injury in multiple sclerosis can help clinicians comprehensively understand the evolution of disease-modifying therapeutic targets of this disorder. Here, the mechanisms of nerve injury in multiple sclerosis and the relationship with the evolution of disease-modifying therapeutic targets are reviewed.

Piperine inhibits the transformation of endothelial cells into fibroblasts / 中华心血管病杂志

Objective@#To investigate the role of piperine on the transformation of endothelial cells into fibroblasts.@*Methods@#Cultured human umbilical vein endothelial cells (HUVECs, 4-6 passage) were used for the main experiments. The transformation models of endothelial cells into fibroblasts were induced by transforming growth factor β (TGF-β) stimulation. HUVECs were divided into 6 groups: control group, TGF-β group and 4 groups treated with various concentrations of piperine (1, 5, 10, 20 μmol/L). CKK-8 was used to detect cell proliferation. The CD31/α-smooth muscle actin (α-SMA) expression level was detected by fluorescent staining. The vascular endothelial cadherin (VE-cadherin)/vimentin expression was detected by immunofluorescence staining. RT-PCR was used detect the mRNA expressions of transformation markers. Western blot was used to detect the protein expression of snail and twist.@*Results@#TGF-β increased HUVECs proliferation (P<0.05), which could be significantly inhibited by 10 and 20 μmol/L of piperine, but not by 1 and 5 μmol/L of piperine. Immunofluorescence results demonstrated that TGF-β increased HUVECs transformation to fibroblasts as shown by downregulated expression of endothelial markers CD31, VE-cadherin, and upregulated expression of α-SMA and vimentin, again, these effects could be attenuated by 10 and 20 μmol/L piperine. The expression levels of collagen type Ⅰ and type Ⅲ were significantly higher in TGF-β group than in control group (P<0.05), significantly lower in TGF-β+10 μmol/L piperine group and TGF-β+20 μmol/L piperine group than in TGF-β group (P<0.05).In addition, RT-PCR results showed that TGF-β increased mRNA expression of transformation markers (snail1, snail2, twist1, twist2), while 10 and 20 μmol/L of piperine could significantly downregulated the mRNA expressions of these markers. The protein expression levels of snail and twist were significantly higher in TGF-β group than in control group (both P<0.05), which was significantly lower in TGF-β+20 μmol/L piperine group than in TGF-β group (both P<0.05).@*Conclusions@#Piperine can inhibit the transformation of endothelial cells into fibroblasts. This effect might be viewed as one of the potential mechanisms of reduced myocardial fibrosis post piperine treatment.