Aim Ulcerative colitis （UC） is an increasingly common condition particularly in developed countries. The lack of satisfactory treatment fuels the search for alternative therapeutic strategies. In the present study, ...Aim Ulcerative colitis （UC） is an increasingly common condition particularly in developed countries. The lack of satisfactory treatment fuels the search for alternative therapeutic strategies. In the present study, we as- sessed the preclinical activity of berberine for the treatment of dextran sodium sulphate （DSS）-induced chronic re- lapsing colitis in C57BL/6 mice. Methods Colitis of mice was induced by three cycles of 2.0% DSS. From day13 onward, colitis mice were orally administered with 20 mg/kg berberine for 30 days. The disease severity was de- termined by daily monitoring the body weight, stool consistency, and stool bleeding of mice. At the end of treat- ment, colons were collected and subjected to histological, RT-qPCR, Western blot, and LC-MS analyses. Lympho- eytes were isolated from spleens and cultured for assessment of eytokine secretion. Results Berberine significantly ameliorated disease severity, colon shortening, histological injuries of colitis mice. Further, berberine treatment consistently and notably regulated DSS-assoeiated increase in mRNAs levels of Thl7-related eytokines （inhibition of IL-17 and ROR-γt） in the colon out of all tested eytokines. Moreover, the increases of TNF-α, IL-6 and IL-23 mRNA, and the phosphorylated STAT3 in colons of DSS - treated mice were significantly reversed by berberine. In addition, berberine directly inhibited TNF-α and IL-17 secretion from cultured lymphoeytes upon PMA/ionomyein -1 re-stimulation. In the meanwhile, a six-time amount of berberine in colon tissue （4.26 ± 2.62 ng · g^-1 colon） was measured when compared that in serum （0.76 ± 0.23 ng · m1^-1） and no detected histological changes was found in major organs of colitis mice. Conclusion We demonstrate for the first time that berberine exerts immuno- modulatory effect in alleviating DSS-indueed chronic relapsing colitis via inhibition of the JAK/STAT signalling acti- vation in the inflamed colon. The demonstration of activity in this model supports the possibility of clinical efficacy of berberine in treating chronic UC.展开更多
Objective:Active and passive smoking are common environmental risk factors,but there is no definite conclusion about their effects on relapse and disability progression in multiple sclerosis(MS)and neuromyelitis optic...Objective:Active and passive smoking are common environmental risk factors,but there is no definite conclusion about their effects on relapse and disability progression in multiple sclerosis(MS)and neuromyelitis optica spectrum disorder(NMOSD).Methods:This was a retrospective cohort study.Patients were included from four centers.Demographic and clinical data were extracted from the clinical database,while data involving environmental exposures during daily life,relapse,and disability progression were obtained through telephone follow-up interviews.Determinants of relapse were assessed by Cox proportional models,and disability progression was assessed by linear regression.Kaplan‒Meier survival was used to estimate relapse within five years after the first attack.Results:A total of 130 MS patients and 318 NMOSD patients were included in this study,and females accounted for 60%and 79.6%,respectively.MS patients with an active smoking history had a higher risk of relapse,for which the association became borderline significant after accounting for covariates(aHR=1.52,95%CI=1.00,2.31;p=0.052).The relapse risk between ever-smokers who smoked more than 10 cigarettes per day and smokers who smoked less than 10 cigarettes per day was not significantly different(aHR=0.96,95%CI=0.63,1.47;p=0.859).However,exposure to passive smoking was associated with a reduced risk of MS relapse(aHR=0.75,95%CI=0.56,1.00;p=0.044)compared with never-exposed patients.No associations were observed between active smoking/passive smoking and the risk of NMOSD relapse,but patients with a history of smoking were associated with a lower annual progression rate by Expanded Disability Status Scale(EDSS)(aβ=−0.20,95%CI=−0.38,−0.01;p=0.036)and Multiple Sclerosis Severity Score(MSSS)(aβ=−0.23,95%CI=−0.44,−0.03;p=0.028).Conclusion:Our research shows that active smoking increases the relapse risk of MS and has a negative impact on disability progression;thus,smoking cessation should be encouraged.展开更多
文摘Aim Ulcerative colitis （UC） is an increasingly common condition particularly in developed countries. The lack of satisfactory treatment fuels the search for alternative therapeutic strategies. In the present study, we as- sessed the preclinical activity of berberine for the treatment of dextran sodium sulphate （DSS）-induced chronic re- lapsing colitis in C57BL/6 mice. Methods Colitis of mice was induced by three cycles of 2.0% DSS. From day13 onward, colitis mice were orally administered with 20 mg/kg berberine for 30 days. The disease severity was de- termined by daily monitoring the body weight, stool consistency, and stool bleeding of mice. At the end of treat- ment, colons were collected and subjected to histological, RT-qPCR, Western blot, and LC-MS analyses. Lympho- eytes were isolated from spleens and cultured for assessment of eytokine secretion. Results Berberine significantly ameliorated disease severity, colon shortening, histological injuries of colitis mice. Further, berberine treatment consistently and notably regulated DSS-assoeiated increase in mRNAs levels of Thl7-related eytokines （inhibition of IL-17 and ROR-γt） in the colon out of all tested eytokines. Moreover, the increases of TNF-α, IL-6 and IL-23 mRNA, and the phosphorylated STAT3 in colons of DSS - treated mice were significantly reversed by berberine. In addition, berberine directly inhibited TNF-α and IL-17 secretion from cultured lymphoeytes upon PMA/ionomyein -1 re-stimulation. In the meanwhile, a six-time amount of berberine in colon tissue （4.26 ± 2.62 ng · g^-1 colon） was measured when compared that in serum （0.76 ± 0.23 ng · m1^-1） and no detected histological changes was found in major organs of colitis mice. Conclusion We demonstrate for the first time that berberine exerts immuno- modulatory effect in alleviating DSS-indueed chronic relapsing colitis via inhibition of the JAK/STAT signalling acti- vation in the inflamed colon. The demonstration of activity in this model supports the possibility of clinical efficacy of berberine in treating chronic UC.
基金supported by the National Natural Science Foundation of China (U20A20357)Program for Innovative Research Team of the First Affiliated Hospital of USTC。
文摘Objective:Active and passive smoking are common environmental risk factors,but there is no definite conclusion about their effects on relapse and disability progression in multiple sclerosis(MS)and neuromyelitis optica spectrum disorder(NMOSD).Methods:This was a retrospective cohort study.Patients were included from four centers.Demographic and clinical data were extracted from the clinical database,while data involving environmental exposures during daily life,relapse,and disability progression were obtained through telephone follow-up interviews.Determinants of relapse were assessed by Cox proportional models,and disability progression was assessed by linear regression.Kaplan‒Meier survival was used to estimate relapse within five years after the first attack.Results:A total of 130 MS patients and 318 NMOSD patients were included in this study,and females accounted for 60%and 79.6%,respectively.MS patients with an active smoking history had a higher risk of relapse,for which the association became borderline significant after accounting for covariates(aHR=1.52,95%CI=1.00,2.31;p=0.052).The relapse risk between ever-smokers who smoked more than 10 cigarettes per day and smokers who smoked less than 10 cigarettes per day was not significantly different(aHR=0.96,95%CI=0.63,1.47;p=0.859).However,exposure to passive smoking was associated with a reduced risk of MS relapse(aHR=0.75,95%CI=0.56,1.00;p=0.044)compared with never-exposed patients.No associations were observed between active smoking/passive smoking and the risk of NMOSD relapse,but patients with a history of smoking were associated with a lower annual progression rate by Expanded Disability Status Scale(EDSS)(aβ=−0.20,95%CI=−0.38,−0.01;p=0.036)and Multiple Sclerosis Severity Score(MSSS)(aβ=−0.23,95%CI=−0.44,−0.03;p=0.028).Conclusion:Our research shows that active smoking increases the relapse risk of MS and has a negative impact on disability progression;thus,smoking cessation should be encouraged.
