Emily M Bradford, Corey A Thompson, Tatiana Goretsky, Terrence A Barrett, Division of Gastroenterology, Department of Internal Medicine, University of Kentucky, Lexington, KY 40536, United States.
World J Gastroenterol. 2017 Jul 28;23(28):5115-5126. doi: 10.3748/wjg.v23.i28.5115.
To assess dietary myo-inositol in reducing stem cell activation in colitis, and validate pβ-catenin as a biomarker of recurrent dysplasia.
We examined the effects of dietary myo-inositol treatment on inflammation, pβ-catenin and pAkt levels by histology and western blot in IL-10 and dextran sodium sulfate-treated colitic mice. Additionally, we assessed nuclear pβ-catenin in patients treated with myo-inositol in a clinical trial, and in patients with and without a history of colitis-induced dysplasia.
In mice, pβ-catenin staining faithfully reported the effects of myo-inositol in reducing inflammation and intestinal stem cell activation. In a pilot clinical trial of myo-inositol administration in patients with a history of low grade dysplasia (LGD), two patients had reduced numbers of intestinal stem cell activation compared to the placebo control patient. In humans, pβ-catenin staining discriminated ulcerative colitis patients with a history of LGD from those with benign disease.
Enumerating crypts with increased numbers of pβ-catenin - positive cells can be utilized as a biomarker in colitis-associated cancer chemoprevention trials.
评估膳食肌醇在减少结肠炎中干细胞激活方面的作用,并验证 pβ-连环蛋白作为复发性异型增生的生物标志物。
我们通过组织学和 Western blot 检测膳食肌醇处理对白细胞介素 10 和葡聚糖硫酸钠处理的结肠炎小鼠炎症、pβ-连环蛋白和 pAkt 水平的影响。此外,我们评估了在临床试验中接受肌醇治疗的患者以及有和无结肠炎相关异型增生病史的患者的核 pβ-连环蛋白。
在小鼠中,pβ-连环蛋白染色忠实地反映了肌醇减少炎症和肠干细胞激活的作用。在肌醇给药治疗低级别异型增生(LGD)病史患者的一项初步临床试验中,与安慰剂对照组患者相比,两名患者的肠干细胞激活数量减少。在人类中,pβ-连环蛋白染色可区分溃疡性结肠炎患者有 LGD 病史和良性疾病患者。
增加 pβ-连环蛋白阳性细胞的隐窝计数可用作结肠炎相关癌症化学预防试验的生物标志物。