RESUMO
BACKGROUND: STIM- and Orai-mediated store operated calcium entry (SOCE) is a ubiquitous Ca2+ signaling process, crucial for the proper function of immune, muscle and neuronal systems. To treat SOCE-related disorder or diseases of these systems, and to mechanistically dissect activation and function of SOCE, specific SOCE inhibitors are needed. However, strategies for developing new SOCE modifiers are still limited.
Methodology: In this study, we identified a novel SOCE inhibitor named 2PHDO from a small pool of Chinese herbal extracts used for treating psoriasis. It could block SOCE and SOCE-mediated NFAT translocation in multiple types of cells with a half inhibitory concentration around 1 µM. At this concentration, 2PHDO was specific for SOCE. Mechanistically, 2PHDO didn't affect the activation of STIM1 or its physical coupling with Orai1. Rather, 2PHDO inhibited SOCE via its actions on Orai1. Results: 2PHDO may serve as a good template for developing new medicines aiming to treat SOCE related diseases. Conclusion: Overall, we proved the feasibility of screening and identification of novel SOCE inhibitors from active monomers of Chinese herbal medicine.RESUMO
BACKGROUND: Bipolar transurethral enucleation and resection of the prostate in saline has recently been considered as a safe and technically feasible endoscopic procedure for symptomatic benign prostatic hyperplasia. However, it has not been accepted widely because of the perception of technical difficulty. METHODS: A retrospective data review was performed of the first consecutive 100 patients who had undergone bipolar transurethral enucleation and resection of prostatic adenoma. Operative outcome, complications, ratio of conversion to conventional transurethral resection of the prostate and efficiency of tissue enucleation and resection were used to assess the learning curve. RESULTS: Bipolar transurethral enucleation and resection of the prostate was successfully performed in 83 patients. The mean operative time was 117.5 min, and the mean indwelling catheterization was 3.3 ± 1.9 days. After 6 months, maximum urinary flow was 21.34 ± 4.09 ml/s, IPSS was 9.66 ± 2.64, and quality of life was 2.31 ± 0.92 with a residual prostate volume of 35.29 ± 17.57 ml. Regarding the learning curve, the ratio of conversion to conventional bipolar transurethral resection of the prostate decreased after 30 cases, and the efficiency of enucleation and resection increased significantly with accumulative experience after 50 cases. CONCLUSIONS: The current results established that bipolar transurethral enucleation and resection of the prostate in saline is a safe and reproducible procedure.