1.Tet: novel anti-tumor drug target based on DNA demethylation
Wei GONG ; Wenli MENGZHOU ; Na TIAN ; Guanqiao LIN ; Tianran FU ; Liang ZHANG
Journal of Shanghai Jiaotong University(Medical Science) 2017;37(4):551-555
Tet (ten-eleven translocation) proteins belong to α-ketoglutaric acid (α-KG or 2-OG) and Fe2+ dependent dioxygenases. Tets are found to be involved in the unique mammalian DNA active demethylation process by specifically oxidizing the methyl group of 5-methylcytosine (5mC) in mammalian genome, and play critical roles in gene regulation in early embryonic development and stem cell differentiation via regulating the dynamic balance distribution of 5mC. Abnormal expression and function of Tets are closely associated with various hematological malignances, including myelodysplastic syndrome, chronic myelomonocytic leukemia, and acute lymphoblastic leukemia, as well as solid tumors. Hence, Tets and Tets-mediated DNA demethylation are novel anti-tumor drug targets. Investigation of biological function and catalytic mechanism of Tets is helpful for further understanding mechanisms of tumor incidence and development relevant to DNA demethylation pathway and can provide reference for developing new anti-tumor targeted drugs.
2.Impacts on urodynamic parameters and the protein expressions of M2 and M3 receptors of detrusor in the rats of detrusor hyperreflexia treated with ginger-salt-isolated moxibustion at "Shenque" (CV 8).
Yi LIU ; Xuerui WANG ; Tianran LI ; Liting LIN ; Guangxia SHI ; Yuanbo FU ; Cunzhi LIU
Chinese Acupuncture & Moxibustion 2017;37(4):401-405
OBJECTIVETo discuss the effects on detrusor hyperreflexia treated with ginger-salt-isolated moxibustion at "Shenque" (CV 8) and its mechanism.
METHODSThirty female adult SD rats were selected. The model of detrusor hyperreflexia was prepared with complete spinal transection at T, of which, 20 rats were randomized into a model group (10 rats) and a moxibustion group (10 rats). A sham-operation group (10 rats) was set up for sham-spinal transection. In the moxibustion group, when urine incontinence occurred (about in 2 weeks of modeling), the ginger-salt-isolated moxibustion at "Shenque" (CV 8) was given, 3 moxa cones each time, once a day, continuously for 7 days. After treatment, in each group, the urodynamic parameters were determined, after which, the bladder detrusor was collected. Western blot was used to determine the protein expressions of M2 and M3 receptors.
RESULTSCompared with the sham-operation group, the micturition interval was shortened apparently (<0.01); the maximal bladder pressure was increased apparently (<0.01); the protein expression of M2 receptor in the detrusor was increased significantly (<0.05) and that of M3 receptor had no apparent change (>0.05) in the rats of the model group. Compared with the model group, the micturition interval was longer apparently (<0.01), the maximal bladder pressure was reduced apparently (<0.01), the protein expression of M2 receptor in the detrusor was reduced significantly (<0.05) and that of M3 receptor had no apparent change (>0.05) in the rats of the moxibustion group.Compared with the sham-operation group, the results of the above indicators were not different significantly in the moxibustion group (all>0.05).
CONCLUSIONSThe ginger-salt-isolated moxibustion at "Shenque" (CV 8) suppresses the overactive bladder in the rat with spinal transection and its effect mechanism is possibly relevant with reducing the protein expression of detrusor M2 and inhibiting the excessive contraction of the detrusor.