Serum Copper and Zinc Levels and Colorectal Cancer in Adults: Findings from the National Health and Nutrition Examination 2011-2016.

Several studies have indicated an association between serum copper and zinc levels and colorectal cancer, but results were controversial. This study assessed the association of serum copper, zinc, and copper/zinc ratio with colorectal cancer in US adults aged 20 years and older through the use of National Health and Nutrition Examination Survey (NHANES) 2011-2016 data. Serum concentrations of copper and zinc were measured using inductively coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS). Odds ratios with 95% confidence intervals (ORs with CIs) were calculated for serum copper, zinc, and copper/zinc ratio by multivariate logistic regression. A total of 4663 participants (2320 males and 2343 females) with 24 colorectal cancer patients were included in the analyses. We did not observe a statistically significant association between serum copper level and colorectal cancer (top vs bottom quartile multivariate OR 1.71; 95% CI, 0.37-7.88; P for trend = 0.429). In addition, serum zinc level was also not significantly associated with colorectal cancer (top vs bottom quartile multivariate OR 0.72; 95% CI, 0.12-4.27; P for trend = 0.346). While in the age- and gender-adjusted model, there seemed to be a trend that participants with higher copper/zinc ratio level had higher odds of colorectal cancer than participants with lower copper/zinc ratio level; no statistically significant association was observed in multivariate-adjusted models. Our findings did not support a significant association between serum copper and zinc level and colorectal cancer risk in the general US population. Furthermore, large longitudinal studies should be needed to confirm these findings.

Involvement of microRNA-23b in TNF-α-reduced BMSC osteogenic differentiation via targeting runx2.

Elucidation of the molecular mechanism governing bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation is of great importance for improving the treatment of osteoporosis. TNF-α is a well-known inhibitory factor during osteogenic differentiation of BMSCs. In our experiment, we consistently observed that TNF-α significantly inhibited BMSC osteogenic differentiation, which was partially rescued by BAY 11-7082 (NF-κB inhibitor). In this study, we examined the potential roles of microRNAs (miRNAs) involved in TNF-α-mediated reduction of BMSC osteogenesis. We found that microRNA-23b (miR-23b) was dramatically induced under the stimulation of TNF-α, which was abolished by BAY 11-7082. Similar to the effect of TNF-α, miR-23b agonist (agomir-23b) obviously impaired BMSC osteogenic differentiation in vitro and in vivo. However, agomir-23b had no effect on osteoclast activity. Overexpression of miR-23b significantly reduced runx2, the master transcription factor during osteogenesis, suggesting that miR-23b acts as an endogenous attenuator of runx2 in BMSCs. Mutation of the putative miR-23b binding site in runx2 mRNA blocked miR-23b-mediated repression of the runx2 3' untranslated region (3'UTR) luciferase reporter activity, suggesting that miR-23b directly binds to runx2 3'UTR. Furthermore, infection with Ad-runx2 (adenovirus carrying the entire CDS sequence of runx2) effectively rescued the inhibition of BMSC osteogenic differentiation in miR-23b-overexpressing cells, indicating that the inhibiting effect of miR-23b on osteogenesis is mediated by suppression of runx2. Moreover, caudal vein injection of agomir-23b notably caused severe osteoporosis in mice, and forced expression of runx2 by combined injecting Ad-runx2 attenuated the bone loss induced by miR-23b. Collectively, these data indicated that miR-23b was involved in TNF-α-mediated reduction of BMSC osteogenesis by targeting runx2. These findings may provide new insights into understanding the regulatory role of miR-23b in the process of BMSC osteogenic differentiation in inflammatory conditions and a novel therapeutic target for osteoporosis.