Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn's Disease Mouse Model.

Mycophenolate mofetil (MMF) is an alternative immunosuppressive agent that has been reported to be effective and well tolerated for the treatment of refractory inflammatory bowel disease (IBD). The aim of this study was to investigate the therapeutic effect of MMF on intestinal injury and tissue inflammation, which were caused by Crohn's disease (CD). Here, trinitrobenzene sulfonic acid-relapsing (TNBS) colitis was induced in mice; then, we measured the differentiation of Th1/Th2 cells in mouse splenocytes by flow cytometry and the secretion of cytokines in mice with TNBS-induced colitis by real-time polymerase chain reaction and/or enzyme-linked immunosorbent assay (RT-PCR/ELISA). The results show that MMF significantly inhibited mRNA expression of pro-inflammatory cytokines IFN-γ, TNF-α, IL-12, IL-6, and IL-1ß in mice with TNBS-induced colitis; however, MMF did not inhibit the expression of IL-10 mRNA. Additionally, ELISA showed that the serum levels of IFN-γ, TNF-α, IL-12, IL-6, and IL-1ß were down-regulated in a TNBS model of colitis. Flow cytometric analysis showed MMF markedly reduced the percentages of Th1 and Th2 splenocytes in the CD mouse model. Mycophenolic acid (MPA) also significantly decreased the percentages of splenic Th1 and Th2 cells in vitro. Furthermore, MMF treatment not only significantly ameliorated diarrhea, and loss of body weight but also abrogated the histopathologic severity and inflammatory response of inflammatory colitis, and increased the survival rate of TNBS-induced colitic mice. These results suggest that treatment with MMF may improve experimental colitis and induce inflammatory response remission of CD by down-regulation of pro-inflammatory cytokines via modulation of the differentiation of Th1/Th2 cells.

Palliative treatment of malignant colorectal obstruction caused by advanced malignancy: a self-expanding metallic stent or surgery? A system review and meta-analysis.

We conducted a meta-analysis to compare the outcomes of a self-expanding metallic stent (SEMS) vs. surgery for the palliative treatment of colorectal obstruction caused by advanced colorectal malignancy. The databases of MEDLINE, EMBASE, Cochrane controlled trials registry and the Chinese Wanfang were retrieved (updated to 31 August 2011) to identify eligible studies. We calculated the odds ratio or weighted mean difference and its corresponding 95 % confidence interval. In total, nine primary studies were included in this analysis. The success rate of SEMS placement was 93.9 %, with short-term and long-term complication rates of 26.2 and 16.1 %, respectively. Combined analyses revealed that the SEMS group had a similar risk of short-term complications as the surgical group (P = 0.22). Moreover, SEMS was not associated with a higher mortality risk than surgical intervention (P = 0.22) and it required a significantly shorter hospitalization time (P < 0.01); however, SEMS patients had a higher risk of long-term complications (P = 0.03). Because of great heterogeneities between patients and chemoradiotherapy, we did not analyze the survival times of the two groups. These results support the feasibility of SEMS as a palliative treatment for malignant colorectal obstruction caused by incurable malignancy, as it requires shorter hospitalization and is followed by quick recovery. However, the risk of long-term complications such as perforation and stent migration should be borne in mind.

Function of macrophage-derived exosomes in chronic liver disease: From pathogenesis to treatment.

Chronic liver disease (CLD) imposes a heavy burden on millions of people worldwide. Despite substantial research on the pathogenesis of CLD disorders, no optimal treatment is currently available for some diseases, such as liver cancer. Exosomes, which are extracellular vesicles, are composed of various cellular components. Exosomes have unique functions in maintaining cellular homeostasis and regulating cell communication, which are associated with the occurrence of disease. Furthermore, they have application potential in diagnosis and treatment by carrying diverse curative payloads. Hepatic macrophages, which are key innate immune cells, show extraordinary heterogeneity and polarization. Hence, macrophage-derived exosomes may play a pivotal role in the initiation and progression of various liver diseases. This review focuses on the effects of macrophage-derived exosomes on liver disease etiology and their therapeutic potential, which will provide new insights into alleviating the global pressure of CLD.