Amlexanox targeted inhibition of TBK1 regulates immune cell function to exacerbate DSS-induced inflammatory bowel disease.

Amlexanox (ALX) is a small molecule drug for the treatment of inflammatory, autoimmune, metabolic and tumor diseases. At present, there are no studies on whether ALX has a therapeutic effect on inflammatory bowel disease (IBD). In this study, we used a mouse model of dextran sulfate sodium (DSS)-induced colitis to investigate the effect of ALX targeted inhibition of TBK1 on colitis. We found that the severity of colitis in mice was correlated with TBK1 expression. Notably, although ALX inhibited the activation of the TBK1-NF-κB/TBK1-IRF3 pro-inflammatory signaling pathway, it exacerbated colitis and reduced survival in mice. The results of drug safety experiments ruled out a relationship between this exacerbating effect and drug toxicity. In addition, ELISA results showed that ALX promoted the secretion of IL-1ß and IFN-α, and inhibited the production of cytokines IL-6, TNF-α, IL-10, TGF-ß and secretory IgA. Flow cytometry results further showed that ALX promoted T cell proliferation, activation and differentiation, and thus played a pro-inflammatory role; Also, ALX inhibited the generation of dendritic cells and the polarization of macrophages to M1 type, thus exerting anti-inflammatory effect. These data suggest that the regulation of ALX on the function of different immune cells is different, so the effect on the inflammatory response is bidirectional. In conclusion, our study demonstrates that simply inhibiting TBK1 in all immune cells is not effective for the treatment of colitis. Further investigation the anti-inflammatory mechanism of ALX on dendritic cells and macrophages may provide a new strategy for the treatment of IBD.

Evaluation of indices in differentiation between iron deficiency anemia and beta-thalassemia trait for Chinese children.

SUMMARY: Iron deficiency anemia (IDA) and beta-thalassemia trait (beta-TT) are the most common microcytic anemia. Kinds of discrimination indices have been established as simple, fast, and inexpensive means since 1970s. This study evaluates the validity of 12 indices in differentiation between IDA and beta-TT for Chinese children. The 12 discrimination indices were red blood cell (RBC) count, RBC distribution width, Mentzer Index, Green and King Index, RBC distribution width Index, England and Fraser Index, Shine and Lal Index, Srivastava Index, Ricerca Index, Ehsani Index, Sirdah Index, and Huber-Herklotz-Index. A total of 300 children (beta-TT, n=127 and IDA, n=173) were enrolled in the study. We calculated the sensitivity and specificity, positive and negative predictive values, and Youden's index for each index. We also established new cut-off values by receiver operating characteristic curves. Green and King Index showed the highest reliability, as it had the largest area under the curve (AUC=0.947), whereas Srivastava Index and Shine and Lal Index showed the lowest reliability (AUC=0.679 and 0.532, respectively). We concluded Green and King Index, Ricerca Index, and England and Fraser Index could be used in discrimination between IDA and beta-TT in Chinese children.