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BackgroundGuizhi-Shaoyao-Zhimu decoction (GSZD) has been extensively used for rheumatoid arthritis (RA) therapy. Marked therapeutic efficacy of GSZD acting on RA has been demonstrated in several long-term clinical trials without any significant side effects. However, its pharmacological mechanisms remain unclear due to a lack of appropriate scientific methodology.MethodsGSZD’s mechanisms of action were investigated using an integrative approach that combined drug target prediction, network analysis, and experimental validation.ResultsA total of 77 putative targets were identified for 165 assessed chemical components of GSZD. After calculating the topological features of the nodes and edges in the created drug-target network, we identified a candidate GSZD-targeted signal axis that contained interactions between two putative GSZD targets [histone deacetylase 1 (HDAC1) and heat shock protein 90 kDa alpha, class A member 1 (HSP90AA1)] and three known RA-related targets [NFKB2; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta (IKBKB); and tumor necrosis factor-alpha (TNF-α)]. This signal axis could connect different functional modules that are significantly associated with various RA-related signaling pathways, including T/B cell receptor, Toll-like receptor, NF-kappa B and TNF pathways, as well as osteoclast differentiation. Furthermore, the therapeutic effects and putative molecular mechanisms of GSZD’s actions on RA were experimentally validated in vitro and in vivo.ConclusionsGSZD may partially attenuate RA by reversing inflammation-immune system imbalance and regulating the HDAC1–HSP90AA1–NFKB2–IKBKB–TNF-α signaling axis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0921-x) contains supplementary material, which is available to authorized users.

Improving zinc (Zn) content in wheat and its processed foods is an effective way to solve human Zn deficiency, which can cause a variety of diseases. This article summarizes the works on Zn in wheat grain, wheat processing, and wheat-derived foods. Grain Zn content in wheat was 31.84 mg•kg −1 globally but varied across continents, for example, 25.10 mg•kg −1 in Europe, 29.00 mg•kg −1 in Africa, 33.63 mg•kg −1 in Asia, and 33.91 mg•kg −1 in North America. Grain Zn content in wheat improved from 28.96 to 36.61 mg•kg −1 and that in flour increased from 10.51 to 14.82 mg•kg −1 after Zn fortification. Furthermore, Zn content varied in the different processed components of wheat; that is, Zn content was 12.58 mg•kg −1 in flour, 70.49 mg•kg −1 in shorts, and 86.45 mg•kg −1 in bran. Zinc content was also different in wheat-derived foods, such as 13.65 mg•kg −1 in baked food, 10.65 mg•kg −1 in fried food, and 8.03 mg•kg −1 in cooking food. Therefore, the suitable Zn fortification, appropriate processing, and food type of wheat are important to meet people's Zn requirement through wheat.

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