Zhao J.,Wuhan University |
Zhao J.,The Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases |
Zhao J.,Peking Union Medical College |
Zhao J.,Sun Yat Sen University |
And 11 more authors.
Oncotarget | Year: 2017
Glutaminolysis is important for metabolism and biosynthesis of cancer cells, and GLS is essential in the process. Selenite is widely regarded as a chemopreventive agent against cancer risk. Emerging evidence suggests that it also has chemotherapeutic potential in various cancer types, but the mechanism remains elusive. We demonstrate for the first time that supranutritional dose of selenite suppresses glutaminolysis by promoting GLS1 protein degradation and apoptosis. Mechanistically, selenite promotes association of APC/C-CDH1 with GLS1 and leads to GLS1 degradation by ubiquitination, this process is related to induction of PTEN expression. In addition, GLS1 expression is increased in human colorectal cancer tissues compared with normal mucosae. Our data provide a novel mechanistic explanation for the anticancer effect of selenite from a perspective of cell metabolism. Moreover, our results indicate that glutaminolysis especially GLS1 could be an attractive therapeutic target in colorectal cancer.
Yu Q.,Wuhan University |
Yu Q.,The Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases |
Zhu S.,Wuhan University |
Zhu S.,The Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases |
And 11 more authors.
PLoS ONE | Year: 2013
Background:Sinomenine, a pure alkaloid isolated in Chinese medicine from the root of Sinomenium acutum, has been demonstrated to have anti-inflammatory and immunosuppressive effects. MicroRNAs (miRNAs) are gradually being recognized as critical mediators of disease pathogenesis via coordinated regulation of molecular effector pathways.Methodology/Findings:After colitis was induced in mice by instillation of 5% (w/v) 2,4,6-trinitrobenzenesulfonic acid (TNBS), sinomenine at a dose of 100 or 200 mg/kg was orally administered once daily for 7 days. We evaluated body weight, survival rate, diarrhea score, histological score and myeloperoxidase (MPO) activity. The mRNA and protein expression levels of miR-155, c-Maf, TNF-α and IFN-γ were determined by quantitative RT-PCR and immunohistochemistry, respectively. Sinomenine (100 or 200 mg/kg)-treated mice with TNBS-induced colitis were significantly improved in terms of body weight, survival rate, diarrhea score, histological score and MPO activity compared with untreated mice. Both dosages of sinomenine significantly decreased the mRNA and protein expression levels of c-Maf, TNF-α and IFN-γ, which elevated in TNBS-induced colitis. Furthermore, sinomenine at a dose of 200 mg/kg significantly decreased the level of miR-155 expression by 71% (p = 0.025) compared with untreated TNBS-induced colitis in mice.Conclusions/Significance:Our study evaluated the effects and potential mechanisms of sinomenine in the anti-inflammatory response via miRNA-155 in mice with TNBS-induced colitis. Our findings suggest that sinomenine has anti-inflammatory effects on TNBS-induced colitis by down-regulating the levels of miR-155 and several related inflammatory cytokines. © 2013 Yu et al.
Chen M.,Wuhan University |
Chen M.,The Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases |
Yi F.,The Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases |
Zhou F.,Wuhan University |
And 8 more authors.
Surgery Today | Year: 2015
Purposes: To establish the risk factors for initial surgery in patients with Crohn’s disease (CD) in Central China. Methods: The subjects of this study were patients with CD treated at Zhongnan Hospital of Wuhan University, an IBD center in Wuhan City, Central China, between January, 1992 and June, 2012. We conducted uni- and multivariate analyses of the risk factors for initial surgery for CD in these patients. Results: A total of 197 patients with CD were included in this study. The cumulative incidence of initial surgery was 21.8, 28.9, and 32.5 %, at 1, 5, and 10 years, respectively, after the onset of symptoms. Analysis using multivariate Cox models showed that the relative risk for initial surgery was lower in patients who were younger than 16 years at diagnosis (HR = 0.57, 95 % CI 0.34–0.96, P = 0.034). The risk increased in patients with stricturing (HR = 4.75, 95 % CI 2.48–9.11), those with CD showing penetrating behavior at diagnosis (HR = 5.14, 95 % CI 2.54–10.39), and those with a history of appendectomy (HR = 1.87, 95 % CI 1.03–3.40). Azathioprine (AZA) treatment appeared to decrease the risk for initial surgery in patients with non-penetrating and non-stricturing CD (HR = 0.14, 95 % CI 0.13–3.10). Conclusion: Age at diagnosis, disease behavior, and a history of appendectomy appeared to have an impact on the risk for initial surgery. AZA treatment might be helpful for decreasing the risk of needing initial surgery for patients in whom stricturing or fistulizing disease has not yet developed. © 2014, Springer Japan.
Shang J.,Wuhan University |
Shang J.,The Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases |
Wang X.,Wuhan University |
Wang X.,The Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases |
And 12 more authors.
Yonsei Medical Journal | Year: 2016
Purpose: The -1237T/C polymorphism of the Toll-like receptor 9 (TLR9) gene has been implicated in the susceptibility of inflammatory bowel diseases (IBDs), but the results remain conflicting. We further investigated this association via meta-analysis. Materials and Methods: Multiple electronic databases were extensively searched until February, 2015. The strength of association was evaluated by calculating the pooled odds ratios (ORs) and 95% confidence intervals (CIs). Results: A total of 2987 cases and 2388 controls from eight studies were analyzed. Overall, association was found between TLR9 -1237T/C polymorphism and the risk of IBDs when all the studies were pooled (recessive model, OR: 1.59, 95% CI: 1.02–2.47, p=0.04; homozygote comparison, OR: 1.62, 95% CI: 1.04–2.52, p=0.03; allele model, OR: 1.13, 95% CI: 1.00–1.27, p=0.05). Stratification by ethnicity indicated an association between TLR9-1237T/C polymorphism and IBDs risk in Caucasians (recessive model, OR: 1.59, 95% CI: 1.02–2.47, p=0.04; homozygote comparison, OR: 1.62, 95% CI: 1.04–2.52, p=0.03; allele model, OR: 1.12, 95% CI: 1.00–1.27, p=0.05). When stratified by disease type, significant correlation were only found in the Crohn’s disease subgroup (recessive model, OR: 1.69, 95% CI: 1.05–2.73, p=0.03; homozygote model, OR: 1.74, 95% CI: 1.07–2.82, p=0.02; allele model, OR: 1.15, 95% CI: 1.01–1.32, p=0.04). Conclusion: The present study suggested that the TLR9 -1237T/C polymorphism might act as a risk factor in the development of IBDs, particularly in Caucasians. © Yonsei University College of Medicine 2016.