BACKGROUND:In recent years, the application of stem cel s to treat autoimmune diseases has become a hot spot. But, studies on umbilical cord blood mesenchymal stem cel s transplantation for the treatment of polymyositis/dermatomyositis are rarely reported. OBJECTIVE:To explore the immunologic mechanism of Th cytokines on the occurrence and development of polymyositis/dermatomyositis by observing the changes in serum interferon-γ, interleukin-4 and interleukin-17 in patients after umbilical cord blood mesenchymal stem cel s transplantation. METHODS:Eighty-one polymyositis/dermatomyositis patients were selected and divided into conventional therapy group (n=44) undergoing glucocorticoid and immunosuppressants therapy and cel transplantation group (n=37) undergoing intravenous infusion of umbilical cord blood mesenchymal stem cel s at a density of (3.5-5.2 )×107 . Dosing regimen was same in the two groups. After fol ow-up of 1, 3, 6 months, the changes of creatine kinase and myodynamia were evaluated;after fol ow-up of 3 and 6 months, lung imaging was evaluated;in the cel transplantation group, interferon-γ, interleukin-4 and interleukin-17 levels were detected before treatment and at 3 and 6 months after treatment. RESULTS AND CONCLUSION:At 1, 3, 6 months after treatment, the creatine kinase level was significantly decreased, and the muscle force grade was significantly increased in both groups (both P<0.001). Compared with the conventional therapy group, the creatine kinase level was lower and the muscle force grade was higher in the cel transplantation group (both P<0.001). Results from lung imaging test showed a remarkable improvement after cel transplantation, and it indicated that umbilical cord blood mesenchymal stem cel s transplantation had good stability. At 6 months after transplantation, the level of interferon-γwas significantly increased, while the interleukin-4 level was decreased significantly (both P<0.01);at 3, 6 months after cel transplantation, the levels of interleukin-17 were significantly decreased (P<0.01). Levels of interleukin-4 and interleukin-17 were positively correlated with the level of creatine kinase at 6 months after cel transplantation (r=0.467, 0.488, both P<0.05), but there was no obvious correlation between the levels of interferon-γand creatine kinase (r=0.213, P>0.05). These findings indicate umbilical cord blood mesenchymal stem cel s transplantation combined with glucocorticoid and immunosuppressants therapy can adjust immune network effects and improve the immune tolerance in polymyositis/dermatomyositis patients, which is safe and effective.

Objective Calculus Bovis(CB)is a kind of valuable traditional Chinese medicine,which has been used in clinic for a long time.It has been shown to have significant anti-stroke,anti-inflammatory and anti-tumor effects.But its mechanism for treating Prostate cancer(PCa)remains unclear.The purpose of this study was to explore the target and mechanism of its action in the treatment of prostate cancer throμgh network pharmacology and in vitro and in vivo experiments.Methods The effective compounds of Calculus Bovis were collected by TCM pharmacology database and analysis platform(TCMSP).Search for potential compound targets in TCMSP.Search the Drμgbank,GeneCards,OMIM,PharmGkb,and TTD databases for disease targets associated with prost cancer.Disease and compound targets were integrated in the STRING database to construct their interaction network(PPI)to reveal the key targets of compound treatment for prostate cancer.In order to elucidate the mechanism of Calculus Bovis in the treatment of prostate cancer,GO functional enrichment and KEGG pathway enrichment analysis were conducted using Cytoscape software.The mechanism of treating prostate cancer with Calculus Bovis was studied in vitro and in vivo.Results A total of 11 compounds with anti-prostate cancer activity were identified.Oleanolic acid,ursolic acid,ergosterol,deoxycorticosterone,methylcholine and cholverdin were potential effective components.A total of 367 targets of Calculus Bovis compounds and 2152 targets of prostate cancer were found.The core targets of Calculus Bovis in the treatment of prostate cancer included TP53,STAT3,AKT1,HSP90AA1,ESR1,SRC,JUN,RELA,CCND1,CDKN1A,EGFR,AR,etc.The biological functions of Calculus Bovis mainly involve oxidative stress response,response to steroid hormones,cell response to chemical stress,peptide-serine modification and phosphorylation,and protein serine/threonine kinase activity.Calculus Bovis treatment of prostate cancer mainly involves PI3K-AKT signaling pathway,TNF signaling pathway,MAPK signaling pathway,etc.In vitro and in vivo experiments showed that Calculus Bovis promoted apoptosis of PC3 cells of prostate cancer by inhibiting PI3K-AKT signaling pathway.Conclusion Calculus Bovis has a therapeutic effect on prostate cancer,and its function is related to inhibiting PI3K-AKT signaling pathway and promoting apoptosis of cancer cells.