Background: Irritable bowel syndrome (IBS) is characterized with abdominal pain, bloating, and changes in bowel habits, and dealing with IBS is still a clinical challenge. The pathogenesis of IBS has been reported to be linked to low-grade mucosal inflammation, and macrophages contribute to the pathological process of this disease. Kurarinone (KAR), a flavanoid derived from Sophora flavescens, has been found medically effective in many inflammatory conditions and cancers. KAR was previously reported to inhibit LPS-induced expression of inflammatory cytokines in macrophages, whether and how KAR regulates the functions of macrophage in IBS remains to be elusive. Methods: We established a TNBS-induced IBS mouse model, in which KAR was administrated, and mucosal cytokine expression was measured by qRT-PCR. Additionally, mouse macrophages were generated in vitro and their responses to LPS were evaluated by flow cytometry and qRT-PCR. AhR +/+ or AhR −/macrophages were transferred into DTx-treated CD11b-DTR transgenic mice to investigate the role of AhR in IBS. We collected colonic biopsies and peripheral blood samples from 64 patients with IBS, and analyzed AhR expression by qRT-PCR. Results: We found KAR effectively alleviated visceral hypersensitivity and maintained intestinal barrier functions in mice with IBS. KAR inhibited LPS-induced macrophage activation and expression of pro-inflammatory genes, while increased anti-inflammatory gene expression including IL-10 in an AhR-dependent manner. Using macrophage-depleted mice, we found that chimera mice with AhR −/macrophages were more susceptible to TNBS-induced IBS and the therapeutic effect of KAR on IBS was significantly impaired in mice with AhR −/macrophages. Additionally, we found AhR expression in macrophages of IBS patients was associated with the disease severity.
Conclusion:Our findings provide new evidences that KAR regulates IBS development via macrophage-intrinsic AhR. KAR might show promise as an immunomodulatory therapeutic agent in treating IBS.
The aim of this study was to examine the effect of non-pharmacological staged interventions on fatigue and dyspnoea in patients with chronic obstructive pulmonary disease. A randomized controlled trial was conducted with 64 patients in a tertiary hospital in China from 2010 to 2011. Patients were randomly assigned to the control group (n = 32), who received routine care, and the intervention group (n = 32), who received additional non-pharmacological staged interventions. The Multidimensional Fatigue Inventory and the five-grade Medical Research Council dyspnoea scale were used to collect data at baseline and after 6 weeks. Compared with the control group, patients in the intervention group had significantly lower scores on general fatigue (P < 0.001), physical fatigue (P < 0.001), reduced activity (P < 0.001) and reduced motivation (P = 0.03) and had better relief of dyspnoea (P = 0.02). Our study showed that non-pharmacological staged interventions were effective in relieving fatigue and dyspnoea in patients with chronic obstructive pulmonary disease.
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