BCCIP binds to and activates its promoter in a YY1-dependent fashion in HCT116 cells.

The restriction of Yin Yang 1 (YY1) at BRCA2 and CDKN1A/p21-interacting protein (BCCIP) transcriptional start site (TSS) proximal region in several human cancer cell lines was found by analyzation of ChIP-Seq database from UCSC Genome Browser (http://genome.ucsc.edu). However, whether the stabilization of YY1 by BCCIP impacts its recruitment in the BCCIP promoter region is unclear. Here, we present evidence that transcriptional regulation of YY1 on BCCIP is closely related to YY1 stability in HCT116 human colon cancer cells. YY1 stabilization was in turn regulated by BCCIP, suggesting the existence of a BCCIP-YY1 feedback loop in regulating BCCIP transcription by the YY1. Overexpression of BCCIP stabilized YY1 while knockdown of BCCIP reduced YY1 protein level. In addition, direct interaction between YY1 and BCCIP was confirmed by coimmunoprecipitation approach. Also, the N-terminus region of BCCIP, including the internal conserved domain (ICD), was responsible for binding with the amino acid 146-270 of YY1. More importantly, YY1 stability was related to the BCCIP/ICD domain-mediated YY1 ubiquitination pathway. Moreover, a limited BCCIP promoter region containing YY1 binding site (CCGCCATC) was tightly associated with the pGL4-BCCIP-Luc luciferase activity. In ChIP assays, shBCCIP lentiviral-mediated YY1 instability decreased recruitment of the YY1 at BCCIP TSS proximal region, which could not be restored by YY1 overexpression. Furthermore, knockdown of YY1 inhibited the binding of BCCIP itself at BCCIP promoter region proximal to TSS, demonstrating that transcriptional regulation of the YY1 on BCCIP can be modulated by BCCIP itself in a YY1-dependent fashion.

[Research of TCM synthetic rehabilitation on the recovery of wrist joint after distal radius fractures].

OBJECTIVE: To evaluate efficacy and advantages of the Traditional Chinese Medicine (TCM) synthetic rehabilitation therapy in the treatment of wrist dysfunction after distal radius fractures. METHODS: From May 2014 to October 2015, 72 patients with distal radius fracture meeting standards were treated using central randomization system for clinical research. All the patients were divided into two groups: 36 patients in test group and 36 in control group. Sixty-nine cases were finished treatment and followed up in the end. The test group fell off 1 case, and the control group fell off 2 cases. The test group was given TCM synthetic rehabilitation (manipulative therapy, joint mobilization, soaking-washing with Chinese medicinal herbs, functional exercise), and the control group was given functional exercise as well as soaking-washing with Chinese medicinal herbs, 3 weeks for both. Five evaluation standards were used in this research, which were grip strength, patient-rated wrist evaluation (PRWE), Gartland and Werley wrist score, self-rating anxiety scale(SAS) and the overall curative effect evaluation. Before treatment(baseline), after 3 weeks of treatment and 3 months after fracture were the three points in time when collected the data. RESULTS: After 3 weeks of treatment and 3 months after fracture, the test group had a significantly better results than those of control group in the PRWE, G-W wrist score and the overall curative effect evaluation(P<0.05). In terms of grip strength recovery, after 3 weeks of treatment, the intergroup difference between the test group and the control group were statistically significant relative to the baseline regarding grip strength of ipsilateral wrist by group t-test(P<0.05). However, the test group and the control group had no statistically significant relative to the baseline at 3 months after fracture in grip strength(P<0.05). For the anxiety of patients, compared with the test group and control group at before and after rehabilitation treatment, the anxiety of both test group and control group cases was eased(P<0.05). However, The degree of anxiety relief in test group and control group cases had no difference(P>0.05). CONCLUSIONS: The TCM synthetic rehabilitation therapy has better curative effects on the treatment of functional disability of wrist joints after distal radius fractures than the general therapy of soaking-washing with Chinese medicinal herbs and functional exercise.

Capsaicin reactivates hMOF in gastric cancer cells and induces cell growth inhibition.

Capsaicin (CAP) is the major pungent component of chili pepper and is being evaluated for use against numerous types of tumors. Although CAP is indicated to target multiple signaling pathways, exact mechanisms of how it disturb cancer cell metablism remain obscure. Recent studies revealed Sirtuin 1 (SIRT1) serves as a potential target of CAP in cancer cells, indicating a direct regulation of cancer cell histone acetylation by capsaicin. The present study evaluated the effect of CAP on gastric cancer (GC) cell lines to understand the mechanism of cell growth inhibition. The results showed that CAP could significantly suppress cell growth, while altering histone acetylation in GC cell lines. Further studies found that hMOF, a major histone acetyltranferase for H4K16, is central to CAP-induced epigenetic changes. Reduced hMOF activity was detected in GC tissues, which could be restored by CAP both in vivo and in vitro. These findings revealed an important role of hMOF-mediated histone acetylation in CAP-directed anti-cancer processes, and suggested CAP as a potential drug for use in gastric cancer prevention and therapy.

Human INO80/YY1 chromatin remodeling complex transcriptionally regulates the BRCA2- and CDKN1A-interacting protein (BCCIP) in cells.

The BCCIP (BRCA2- and CDKN1A-interacting protein) is an important cofactor for BRCA2 in tumor suppression. Although the low expression of BCCIP is observed in multiple clinically diagnosed primary tumor tissues such as ovarian cancer, renal cell carcinoma and colorectal carcinoma, the mechanism of how BCCIP is regulated in cells is still unclear. The human INO80/YY1 chromatin remodeling complex composed of 15 subunits catalyzes ATP-dependent sliding of nucleosomes along DNA. Here, we first report that BCCIP is a novel target gene of the INO80/YY1 complex by presenting a series of experimental evidence. Gene expression studies combined with siRNA knockdown data locked candidate genes including BCCIP of the INO80/YY1 complex. Silencing or over-expressing the subunits of the INO80/YY1 complex regulates the expression level of BCCIP both in mRNA and proteins in cells. Also, the functions of INO80/YY1 complex in regulating the transactivation of BCCIP were confirmed by luciferase reporter assays. Chromatin immunoprecipitation (ChIP) experiments clarify the enrichment of INO80 and YY1 at +0.17 kb downstream of the BCCIP transcriptional start site. However, this enrichment is significantly inhibited by either knocking down INO80 or YY1, suggesting the existence of both INO80 and YY1 is required for recruiting the INO80/YY1 complex to BCCIP promoter region. Our findings strongly indicate that BCCIP is a potential target gene of the INO80/YY1 complex.

[Case-control study on tibetan Baimai ointment (see symbol in text) for the treatment of wrist-dysfunction after distal radius fracture].

OBJECTIVE: To evaluate efficacy and safety of Baimai ointment (see symbol in text) in the treatment of wrist-dysfunction after distal radius fracture. METHODS: From April, 2011 to June, 2012, 43 patients with distal radius fracture were treated with plaster fixation. All the patients were divided into two group: test group and control group. Twenty-one patients in test group and 22 in control group, and the baseline was balance (P > 0.05). The 21 patients in test group were treated with Baimai ointment (see symbol in text), fomentation, functional exercises. The 22 patients in control group were treated with placebo, fomentation, functional exercises. Foment affected side wrist with wet towel in 20 min before medication, with the temperature between 50 degrees C and 60 degrees C. Smear drugs uniformly in range of 3 cm in the vicinity of palm stripes after drying (about 3 g) and take functional exercises for the activities of wrist and hand. Continuous follow the program per 8 hours once and follow-up for 8 weeks. The Wrist's pain was assessed with VAS. The wrist's activities were measured with the protractor of orthopedic. Measure The grip strength was measured with dynamometer. The wrist's function were assessed with the table of Cooney. RESULTS: The test group had a significantly better results than those of control group in the extent of wrist's pain throughout the treatment (P < 0.001), and grip strength on the 28th day and the 56th day (P < 0.05), and Cooney functional assessment on the 56th day (P < 0.05). Wrist's activities had no significane difference throughout the 8 weeks (P > 0.05). There were no drug adverse reactions occurred. CONCLUSION: Tibetan Baimai ointment (see symbol in text) has the treatment of wrist-dysfunction after distal radius fracture for external use, which can reduce the extent of wrist's pain, promote grip strength recovery in the middle and late of process, promote wrist's function recovery latterly, and safety for external use.