We have previously shown that compound-7g inhibits colorectal cancer cell proliferation and survival by inducing cell cycle arrest and PI3K/AKT/mTOR pathway blockage. However, whether it has the ability to exert antitumor activity in other cancer cells and what is the exact molecular mechanism for its antiproliferation effect remained to be determined. In the present study, compound-7g exhibited strong activity in suppressing proliferation and growth of glioblastoma cells. The inhibitor selectively downregulated F-box protein SKP2 expression and upregulated cell cycle inhibitor p27, and then resulted in G1 cell cycle arrest. Mechanism analysis revealed that compound-7g also provokes the down-regulation of E2F-1, which acts as a transcriptional factor of SKP2. Further results indicated that compound-7g induced an increase of LC3B-II and p62, which causes a suppression of fusion between autophagosome and lysosome. Moreover, compound-7g mediated autophagic flux blockage promoted accumulation of ubiquitinated proteins and then led to endoplasmic reticulum stress. Our study thus demonstrated that pharmacological inactivation of E2F-1-SKP2-p27 axis is a promising target for restricting cancer progression.

Objective To investigate the predisposing conditions, etiology and clinical characteristics of recurrent bacterial meningitis (RBM) in children.Methods Seventy patients of RBM treated in Beijing Children's Hospital from January 2006 through December 2018 were retrospectively analyzed.Results Predisposing conditions of RBM include: inner ear malformations 24(34.3%), dermal sinus tracts 15(21.4%), head trauma 15(21.4%), meningoencephalocele 12(17.1%), and immune deficiency 4(5.7%). Sixty-seven occasions of meningitis had positive bacterial cultures. Thirty-one occasions of Streptococcus pneumoniae ( S. pneumonia ) meningitis and 3 occasions of Haemophilus influenzae type b (Hib) meningitis occurred in the 24 patients with inner ear malformations; Seventeen occasions of S. pneumonia meningitis occurred in the 15 patients with head trauma, while 8 occasions of S. pneumonia meningitis in 12 patients with Meningoencephalocele; There were 2 Enterococcus faecalis meningitis, 1 Escherichia coli meningitis and 1 Staphylococcus aureus meningitis in 15 patients with dermal sinus tracts; Two of 4 patients with immune deficiency suffered S. pneumoniae meningitis.Conclusions Predisposing conditions of RBM in children include inner ear malformations, head trauma, meningoencephalocele, dermal sinus tracts, and immune deficiency. The most common etiology of RBM with inner ear malformation, head trauma, meningoencephalocele, and immune deficiency is S. pneumoniae . Empiric antibiotic treatment of RBM in children should cover S. pneumoniae.