Nitazoxanide protects against experimental ulcerative colitis through improving intestinal barrier and inhibiting inflammation.

Ulcerative colitis is a chronic disease with colonic mucosa injury. Nitazoxanide is an antiprotozoal drug in clinic. Nitazoxanide and its metabolite tizoxanide have been demonstrated to activate AMPK and inhibit inflammation, therefore, the aim of the present study is to investigate the effect of nitazoxanide on dextran sulfate sodium (DSS)-induced colitis and the underlying mechanism. Oral administration of nitazoxanide ameliorated the symptoms of mice with DSS-induced colitis, as evidenced by improving the increased disease activity index (DAI), the decreased body weight, and the shortened colon length. Oral administration of nitazoxanide ameliorated DSS-induced intestinal barrier dysfunction and reduced IL-6 and IL-17 expression in colon tissues. Mechanistically, nitazoxanide and its metabolite tizoxanide treatment activated AMPK and inhibited JAK2/STAT3 signals. Nitazoxanide and tizoxanide treatment increased caudal type homeobox 2 (CDX2) expression, increased alkaline phosphatase (ALP) activity and promoted tight junctions in Caco-2 cells. Nitazoxanide and tizoxanide treatment restored the decreased zonula occludens-1(ZO-1) and occludin protein levels induced by LPS or IL-6 in Caco-2 cells. On the other hand, nitazoxanide and tizoxanide regulated macrophage bias toward M2 polarization, as evidenced by the increased arginase-1expression in bone marrow-derived macrophages (BMDM). Nitazoxanide and tizoxanide reduced the increased IL-6, iNOS and CCL2 pro-inflammatory gene expressions and inhibited JAK2/STAT3 activation in BMDM induced by LPS. In conclusion, nitazoxanide protects against DSS-induced ulcerative colitis in mice through improving intestinal barrier and inhibiting inflammation and the underlying mechanism involves AMPK activation and JAK2/STAT3 inhibition.

[Construction and optimization of ecological network in Xi'an based on landscape analysis]. / 基于景观分析的西安市生态网络构建与优化.

Ecological network can connect fragmented habitat patches to increase the connectivity among landscapes, which plays an important role to landscapes and ecological problems caused by urbanization. In this study, the ecological networks of Xi'an City were constructed using landscape pattern index and morphological spatial pattern analysis to reveal landscape pattern features. The performance of the network was evaluated with the gravity model to provide an optimization strategy. The landscape richness index was relatively high, with significant differences of landscape patterns between north and south parts. The ecological sources were predominated in the south and east areas, while a higher comprehensive resistance with low connectivity was found in the north and central areas. The ecological corridors were unevenly distributed, with the radiation channels derived from hydrological analysis providing a supplementary role. Furthermore, ecological networks could be optimized by introducing other ecological sources, supplementing stepping stones, and repairing fracture points, to reduce the problems of uneven distribution of ecological sources, the excessively long ecological corridors in local regions, and the obstruction of road networks. Our optimization method provided an optional way to assist urban planning of Xi'an City.