Objective To investigate the expression of microRNA (miRNA)-10a in the intestinal mucosa,serum and peripheral blood mononuclear cell (PBMC) of patients with inflammatory bowel disease (IBD) and explore its role and relevance in the pathogenesis of the disease.Methods The intestinal or colonic mucosal biopsy specimens of nine active ulcerative colitis (UC) patients,11 active Crohn's disease (CD) patients and eight patients with negative colonoscopy result as control were collected.The sera of 12 active UC patients,13 active CD patients and nine healthy controls were collected.The PBMC of nine active UC patients,11 active CD patients and eight healthy controls were collected.The expression of miRNA-10a in the intestinal mucosa,sera and PBMC and the expression of IL-12/IL-23 p40 in the intestinal mucosa were detected by real-time polymerase chain reaction (PCR).Each 8 cases of active UC and CD patients were collected.The intestinal mucosa before infliximab (IFX) treatment and six weeks after three times of IFX treatment were collected.And at same time,the intestinal mucosa of 11 active UC patients and 10 active CD patients were collected and cultured for 18 hours stimulated with IFX in vitro and then the expression of miRNA-10a in the intestinal mucosa was tested.One-way analysis of variance was used for comparison in three samples.Paired t-test was used for two samples comparison.Spearman test was used for correlation analysis.Results Compared with healthy controls,the expression of miRNA-10a in the intestinal mucosa,serum and PBMC of UC and CD patients significantly decreased (F=38.45,30.46 and 14.74,all P＜0.05).There was no statistic significance between UC and CD groups.The expression of IL-12/IL-23 p40 in the intestinal mucosa of UC and CD patients significantly increased (F=32.90,P＜0.05).The expression of IL-12/IL-23 p40 was negatively correlated with the expression of miRNA-10a in the intestinal mucosa of CD patients.After three times of IFX treatment,the expression of miR-10a in the intestinal mucosa of IBD patients significantly increased (t=3.341,3.382,both P＜0.05).After stimulated with IFX in vitro,the expression of miRNA-10a in the intestinal mucosa significantly increased (t=3.095,7.193,both P＜0.05).Conclusions miRNA-10a was closely correlated with the inflammation of IBD patients and with the role of targeting IL-12/IL-23 p40.miRNA-10a might be a new target for the IBD treatment.

BACKGROUND:Berberine has the potential to induce osteogenic differentiation of various mesenchymal stem cells under normal conditions and special conditions such as high glucose,infection and inflammation.It is a natural small molecule drug that can induce bone formation in seed cells instead of growth factors,and has great application prospect in bone tissue engineering. OBJECTIVE:To review and summarize the research progress in the osteogenic mechanism and efficacy of berberine,especially its osteogenic potential under high glucose,infection and inflammation conditions,and its biological safety,so as to provide theoretical basis for its development and application in bone tissue engineering. METHODS:PubMed,WanFang,and CNKI were searched for relevant literature using the keywords of"berberine,bone defects,bone repair,bone regeneration,osteoinductive,osteoporosis,osteoblast,osteoclast,bone tissue engineering,bone,high glucose,diabetes,inflam*,infect*"in English and Chinese,respectively.A total of 105 literatures were selected for review. RESULTS AND CONCLUSION:Berberine can be used to treat multiple diseases including bone diseases,and it has the ability to promote bone regeneration.This article systematically reviews the mechanism of berberine on bone regeneration and in vivo and in vitro studies.Studies have shown that it can play a role in bone repair by promoting osteogenesis,inhibiting osteoclast formation and activity,and preventing osteoporosis.It shows excellent osteogenic differentiation potential mainly via Wnt/β-catenin,PI3K/AKT,EGFR/MEK/p38MAPK,cAMP/PKA/CREB,ERK and other signaling pathways.Berberine can also relieve the inhibition of osteogenic differentiation caused by high glucose,infection and inflammation,which provides more possibilities for the treatment of bone defects in patients with diabetes or infection and inflammation in the bone defect site.Berberine also has the advantages of low toxicity,low price,easy access(currently it can be synthesized),which is a relatively ideal bone induction potential drug.In recent years,the application of berberine in the treatment of bone defect tends to be localized,mainly through the combination with bone tissue engineering technology to improve bioavailability,and has shown good bone repair effect and excellent biological safety in animal experiments.In addition,preclinical experiments have shown splendid bone regeneration potential in the conditions of diabetes,local infection and inflammation.In the future,more studies are needed to fully reveal the osteogenic mechanism and biological safety of berberine,and seek the most suitable controlled release loading system to make artificial bone replacement materials with good mechanical strength,efficacy and biological safety.