The majority of premalignant gastric lesions develop in the mucosa that has been modified by chronic inflammation. As components of the gastritis microenvironment, mesenchymal stem cells (MSCs) and macrophages are critically involved in the initiation and development of the chronic gastritis-associated gastric epithelial lesions/malignancy process. However, in this process, the underlying mechanism of macrophages interacting with MSCs, particularly the effect of macrophages on MSCs phenotype and function remains to be elucidated. The present study revealed that human umbilical cord-derived MSCs were induced to differentiate into cancer-associated fibroblasts (CAFs) phenotype by co-culture with macrophages (THP-1 cells) in vitro, and which resulted in gastric epithelial lesions/potential malignancy via epithelial-mesenchymal transition-like changes. The results of the present study indicated that macrophages could induce MSCs to acquire CAF-like features and a pro-inflammatory phenotype to remodel the inflammatory microenvironment, which could potentiate oncogenic transformation of gastric epithelium cells. The present study provides potential targets and options for inflammation-associated gastric cancer prevention and intervention.
BackgroundMany observational studies have shown that exposure to fluoride in drinking water is associated with hip fracture risk. However, the findings are varied or even contradictory. In this work, we performed a meta-analysis to assess the relationship between fluoride exposure and hip fracture risk.MethodsPubMed and EMBASE databases were searched to identify relevant observational studies from the time of inception until March 2014 without restrictions. Data from the included studies were extracted and analyzed by two authors. Summary relative risks (RRs) with corresponding 95% confidence intervals (CIs) were pooled using random- or fixed-effects models as appropriate. Sensitivity analyses and meta-regression were conducted to explore possible explanations for heterogeneity. Finally, publication bias was assessed.ResultsFourteen observational studies involving thirteen cohort studies and one case-control study were included in the meta-analysis. Exposure to fluoride in drinking water does not significantly increase the incidence of hip fracture (RRs, 1.05; 95% CIs, 0.96–1.15). Sensitivity analyses based on adjustment for covariates, effect measure, country, sex, sample size, quality of Newcastle–Ottawa Scale scores, and follow-up period validated the strength of the results. Meta-regression showed that country, gender, quality of Newcastle–Ottawa Scale scores, adjustment for covariates and sample size were not sources of heterogeneity. Little evidence of publication bias was observed.ConclusionThe present meta-analysis suggests that chronic fluoride exposure from drinking water does not significantly increase the risk of hip fracture. Given the potential confounding factors and exposure misclassification, further large-scale, high-quality studies are needed to evaluate the association between exposure to fluoride in drinking water and hip fracture risk.
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