Design, Synthesis and Biological Evaluation of Glycosylated Derivatives of Silibinin as Potential Anti-Tumor Agents.

Objective: Silibinin, a natural product extracted from the seeds of the Silybum marianum, is versatile with various pharmacological effects. However, its clinical application was strongly hampered by its low bioavailability and poor water solubility. Herein, a series of glycosylated silibinin derivatives were identified as novel anti-tumor agents. Materials and Methods: The cell viability was evaluated by CCK8 assay. Furthermore, cell apoptosis and cell cycle progression were tested by flow cytometry. In addition, the pharmacokinetic assessment of compound 15 and silibinin through intravenous administration (i.v., 2 mg/kg) to ICR mice were performed. Results: The synthesized compounds showed better water solubilities than silibinin. Among them, compound 15 exhibited inhibitory activity against DU145 cells with IC50 value of 1.37 ± 0.140 µM. Moreover, it arrested cell cycle at G2/M phase and induced apoptosis in DU145 cells. Additionally, compound 15 also displayed longer half-life (T1/2 = 128.3 min) in liver microsomes than that of silibinin (T1/2 = 82.5 min) and appropriate pharmacokinetic parameters in mice. Conclusion: Overall, glycosylation of silibinin would be a valid strategy for the development of silibinin derivatives as anti-tumor agents.

Effect of Pars Plana Vitrectomy With or Without Cataract Surgery in Patients with Diabetes: A Systematic Review and Meta-Analysis.

INTRODUCTION: Pars plana vitrectomy (PPV) is considered to be an essential and effective surgical approach for the management of complications of diabetic retinopathy. Given the high rate of accelerated cataract progression after PPV, PPV combined with cataract surgery appears to be an attractive treatment option for patients with diabetes. However, this combined surgical approach remains controversial in terms of effectiveness and safety. We have therefore conducted a meta-analysis to evaluate the treatment outcome of PPV with or without cataract surgery. METHODS: A systematic search of three electronic databases (PubMed, Web of Science, and the Cochrane Library) was performed to identify relevant articles, using the key words "pars plana vitrectomy," "cataract," and "diabetic retinopathy." Main outcome measures included the final visual acuity and postoperative complications. The incidence of postoperative complications was pooled using odds ratio (OR) with 95% confidence intervals in a random effect model. RESULTS: Ultimately, one randomized controlled trial (RCT) and four high-quality retrospective studies met the inclusion criteria and were included in the meta-analysis. In four of these studies, final visual acuity did not vary significantly between patients undergoing PPV alone and those undergoing PPV combined with cataract surgery (combined surgery). Only one study reported better visual improvement in the combined treatment group. Our analysis also showed that most phakic eyes after PPV had cataract progression with varying degrees. In addition, patients receiving PPV alone had a lower risk of neovascular glaucoma (OR 0.36; P < 0.05), iris synechias to anterior capsule (OR 0.36; P < 0.05), and iris rubeosis (OR 0.26; P < 0.05) compared with those receiving combined surgery. CONCLUSION: Overall, our findings show that PPV combined with cataract surgery achieved good outcomes without a substantial increased risk to visual acuity or most complications. Given the high rates of cataract progression after PPV, combined surgery may be the more appropriate treatment for patients with diabetes and coexistent visually significant cataract.