Discovery of anti-allergic components in Guomingkang Formula using sensitive HEMT biochips coupled with in vitro and in vivo validation.

BACKGROUND: Allergic rhinitis (AR) is a prevalent allergic disease, which seriously affects the sufferers' life quality and increases the socioeconomic burden. Guominkang (GMK), a well-known prescription for AR treatment, showed satisfactory effects; while its anti-allergic components remain to be disclosed. AlGaN/GaN HEMT biochip is more sensitive and cost-effective than other binding equipments, indicating its great potential for screening of active ingredients from herbal medicines. METHODS: AR mouse models were first established to test the anti-allergic effect of GMK and discover the ingredients absorbed into blood by ultra-high performance liquid chromatography-mass spectra (UHPLC-MS). Then, novel Syk/Lyn/Fyn-functionalized high electron mobility transistor (HEMT) biochips with high sensitivity and specificity were constructed and applied to screen the active components. Finally, the results from HEMT biochips screening were validated via in silico (molecular docking and molecular dynamics simulation), in vitro (RBL-2H3 cells), and in vivo (PCA mice model) assays. RESULTS: GMK showed a potent therapeutic effect on AR mice, and fifteen components were identified from the medicated plasma. Furthermore, hamaudol was firstly found to selectively inhibit the Syk and Lyn, and emodin was to selectively inhibit Lyn, which were further confirmed by isothermal titration calorimetry, molecular docking, and molecular dynamics simulation analyses. Suppression of the activation of FcεRI-MAPK signals might be the possible mechanism of the anti-allergic effect of hamaudol. CONCLUSIONS: The targets of emodin and hamaudol were discovered by HEMT biochips for the first time. This study provided a novel and effective strategy to discover active components in a complex herbal formula by using AlGaN/GaN HEMT biochips.

[Case control study on clinical effects of sacrococcygeal manipulation in the treatment of coccyx pain].

OBJECTIVE: To study the clinical efficacy of sacral manual therapy in the treatment of coccygodynia. METHODS: From November 2013 to July 2015, 184 patients with sacrococcygeal pain were divided into treatment group and control group. There were 26 males and 65 females in the treatment group, with an average age of (39.63±11.62) years old. In the control group, there were 31 males and 62 females, with an average age of (41.47±11.56) years old. The patients in the treatment group were treated with sacrococcygeal massage therapy, 3 times a week for 2 weeks. The patients in the control group were treated with Diclofenac Diethylamine Emulgel, 2 times a day for 2 weeks. The VAS pain score, score in rating scale of sacrococcygeal pain and degree of tenderness were obtained on the first day of treatment, 2, 7, 14 days and 3 months after treatment to evaluate clinical results. RESULTS: When comparing the VAS pain score of sacrococcygeal pain within the two groups, the differences began to reach statistical significance on the second day(P<0.001). The chagne of VAS pain scores, the change of scores in rating scale of sacrococcygeal pain and the degree of tenderness in the treatment group were all significontly larger that those in the contral group from the second day. CONCLUSIONS: The curative effect of sacral manipulation group is better than that of Diclofenac Diethylamine Emulgel group in the treatment of sacrococcygeal pain.

The transcription factor Yin Yang 1 is essential for oligodendrocyte progenitor differentiation.

The progression of progenitors to oligodendrocytes requires proliferative arrest and the activation of a transcriptional program of differentiation. While regulation of cell cycle exit has been extensively characterized, the molecular mechanisms responsible for the initiation of differentiation remain ill-defined. Here, we identify the transcription factor Yin Yang 1 (YY1) as a critical regulator of oligodendrocyte progenitor differentiation. Conditional ablation of yy1 in the oligodendrocyte lineage in vivo induces a phenotype characterized by defective myelination, ataxia, and tremor. At the cellular level, lack of yy1 arrests differentiation of oligodendrocyte progenitors after they exit from the cell cycle. At the molecular level, YY1 acts as a lineage-specific repressor of transcriptional inhibitors of myelin gene expression (Tcf4 and Id4), by recruiting histone deacetylase-1 to their promoters during oligodendrocyte differentiation. Thus, we identify YY1 as an essential component of the transcriptional network regulating the transition of oligodendrocyte progenitors from cell cycle exit to differentiation.