The "target + activity" method for rapid discovery of active compounds targeting Hsp90 in pancreatic cancer cells from Physalis angulata L / 药学学报

The purpose of this study was to select the active compounds targeting Hsp90 protein in pancreatic cancer cells through a new dual "target + activity" rapid discovery technique. We combined an in vitro anti-cancer activity screening method with a dual-luciferase reporter gene and multi-chromatography separation technology, for rapid discovery of potential Hsp90 inhibitors from the Chinese herbal medicine Physalis angulata L. The anti-proliferation activity of those compounds was assessed in pancreatic cancer cell line BxPC-3 by MTT assays. The molecular mechanisms of Hsp90 inhibition were explored by Western blot and shRNA knockdown assays. As a result, two withanolides, withanolide E (WE) and 4β-hydroxywithanolide E (HWE), were identified from Physalis angulata L. The half maximal inhibitory concentration (IC50) of WE and HWE were 0.71±0.03 and 1.23±0.10 μmol·L-1 for the growth of BxPC-3 cells in 48 h. Luciferase reporter assay demonstrated that WE and HWE significantly induced heat shock element (HSE) activity in a dose- and time-dependent manner. The molecular mechanism study showed that after exposing to 5 μmol·L-1 WE or HWE for 48 h, the aggregation of Hsp90 dimer was upregulated to 6.5±1.3 and 11.8±2.0 fold, while the expression of Hsp90 client protein Akt was downregulated to 21.7%±2.8% and 9.8%±1.4% of the control group. Moreover, the Hsp90 inhibitory activity of WE or HWE was canceled by shRNA mediated Hsp90 knockdown. Overall, based on the dual "target + active" rapid discovery technique, two new Hsp90 inhibitors WE and HWE were found from Physalis angulata L. The Hsp90 inhibitory mechanism of WE and HWE may be mediated by induction of Hsp90 aggregate dimer and inhibition of Hsp90 client protein Akt expression.

Latest progress of BIGH3 gene in corneal diseases and diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#BIGH3 gene plays an important role in ocular diseases. On the one hand, it is closely related to the occurrence of corneal diseases. BIGH3 gene can inhibit corneal neovascularization, lead to corneal dystrophy, participate in keratoconus formation. On the other hand, it can lead to the formation of neovascularization in diabetic retinopathy. The latest experiments show that TGF beta secreted by macrophages can promote the expression of BIGH3 mRNA and BIGH3 protein, and promote apoptosis of retinal endothelial cells and pericytes, which leads to the formation of neovascularization in diabetic retinopathy. This article will describe the new progress of BIGH3 gene in ocular diseases from several aspects as mentioned above.

Research advances of miR-126 and ophthalmic diseases / 国际眼科杂志(Guoji Yanke Zazhi)

Up to now, a variety of microRNAs have been found in a number of studies, that specifically expressed in retinal neuroepithelial, lens, cornea and retinal pigment epithelium, in which miR-126 plays a certain role in the proliferation of tumor cells, the development of thymus lymphocytes and cardiovascular diseases.Some researches show that miR-126 has certain correlations with the formation of corneal neovascularization, the development of diabetic retinopathy, and the immune system related eye disease.In this paper, the current miR-126 in the role of eye disease mechanism and research progress were reviewed.

Long-term surgical outcomes of primary congenital glaucoma in China

OBJECTIVE: To evaluate the long-term outcomes of three surgical procedures for the treatment of primary congenital glaucoma (PCG). INTRODUCTION: PCG is one of the main causes of blindness in children. There is a paucity of contemporary data on PCG in China. METHODS: A retrospective study of 48 patients (81 eyes) with PCG who underwent primary trabeculectomy, trabeculotomy, or combined trabeculotomy and trabeculectomy (CTT). RESULTS: All patients were less than 4 years (yrs) of age, with a mean age of 2.08 ¡À 1.23 yrs. The mean duration of follow-up was 5.49 ¡À 3.09 yrs. The difference in success rates among the three surgical procedures at 1, 3, 6 and 9 yrs was not statistically significant (p = 0.492). However, in patients with over 4 yrs of follow-up, Kaplan-Meier survival analysis revealed that the success rates of trabeculectomy and CTT declined more slowly than that of trabeculotomy. Among the patients, 66.22% acquired good vision (VA ¡Ý 0.4), 17.57% acquired fair vision (VA = 0.1 - 0.3), and 16.22% acquired poor vision (VA < 0.1). The patients with good vision were mostly in the successful surgery group. Myopia was more prevalent postoperatively (p = 0.009). Reductions in the cup-disc ratio and corneal diameter were only seen in the successful surgery group (p = 0.000). In addition, the successful surgery group contained more patients that complied with a regular follow-up routine (p = 0.002). DISCUSSION: Our cases were all primary surgeries. Primary trabeculectomy was performed in many cases because no treatment was sought until an advanced stage of disease had been reached. CONCLUSIONS: In contrast to most reports, in the present study, trabeculectomy and CTT achieved higher long-term success rates than trabeculotomy. The patients with successful surgical results had better vision. Compliance with a routine of regular follow-up may increase the chances of a successful surgical outcome.