Garcinone E Blocks Autophagy Through Lysosomal Functional Destruction in Ovarian Cancer Cells

Background: High proliferative rate of cancer cells requires autophagy to maintain nutrient supply and intracellular homeostasis. As a result, impairing autophagic flux could be a novel strategy of cancer therapy. Aims and Objectives: In this study, the mechanism of a xanthone derivative isolated from Garcinia mangostana, garcinone E(GE), was investigated. Materials and Methods: Fluorescence assay was used to observe the accumulation and location of autophagosome and lysosome. Flow cytometry with Lyso-tracker red, MDC, and AO staining were applied to evaluate the lysosome accumulation and cellular acidity. Western blot and RT-qPCR were performed to evaluate the protein and mRNA levels, respectively. Results: GE could cause enhancement of LC3 II and p62 and the accumulation of autophagosome and lysosome. Meanwhile, it limited the protein level of Rab7, increased lysosomal pH, and inhibited the maturation of lysosomal hydrolases such as Cathepsin L, therefore blockaded the fusion of autophagosome and lysosome. Moreover, GE acted as a TFEB modulator by downregulating its protein level, which might contribute to autophagy dysfunction in ovarian cancer cells. Conclusions: GE interfered autophagosome–lysosome fusion in cancer cells, which demonstrated its application as an autophagy regulator and a potential therapeutic agent.     

TFEB易位肾细胞癌1例并文献复习

目的 报道1例TFEB易位肾细胞癌并进行文献复习,探讨TFEB易位肾细胞癌的临床及影像特点,以期提高对该病的认识。方法 回顾性分析1例TFEB易位肾细胞癌的临床及影像资料,并以中国知网、万方数据知识服务平台及PubMed等为数据来源,通过“TFEB易位肾细胞癌”、“MiT家族易位性肾细胞癌”、“6p21 translocation renal cell carcinoma”以及“t (6;11)(p21;q12)”等关键词进行文献检索,筛选出从2010年1月以来公开发表的且有影像学资料的中英文文献,分析TFEB易位肾细胞癌的临床及影像特点。结果 本例为男性,54岁,腰痛伴肉眼血尿,CT平扫表现为边界清楚、囊实性肿块,伴出血及钙化,增强扫描呈不均匀强化,无远处转移。文献报道的13例确诊病例：男女比例为8∶5;平均年龄为37.8岁;肿块平均最大径约7.7 cm;均进行了手术切除,其中1例术前出现双肺转移,其余12例均无转移。影像学方面,肿块多边界清楚,以囊实性混杂密度为主,强化方式以持续的轻中度强化为主。结论 TFEB易位肾细胞癌是一种少见的非侵袭性低度恶性肿瘤,发生于年轻患者、表现为边界...     

Trehalose-Induced Activation of Autophagy Improves Cardiac Remodeling After Myocardial Infarction

Background

Trehalose (TRE) is a natural, nonreducing disaccharide synthesized by lower organisms. TRE exhibits an extraordinary ability to protect cells against different kinds of stresses through activation of autophagy. However, the effect of TRE on the heart during stress has never been tested.