No abstract

We have previously reported that seventy percent ethanol extract of Chrysanthemum indicum Linne (CIE) strongly reduces Epstein-Barr virus (EBV)-transformed lymphoblastoid cell line (LCL) survival by inhibiting virus-encoded latent infection membrane protein 1 (LMP1)-induced NF-κB activation. To identify an active compound(s) in CIE that inhibits LMP1-induced NF-κB activation, activity-guided fractionation was employed. The CH2Cl2 fraction of CIE strongly reduced LMP1-induced NF-κB activation and LCL viability with relatively low cytotoxic effects on primary human foreskin fibroblast (HFF), HeLa or Burkitt’s lymphoma (BL41) cells. Furthermore, lupeol, a pentacyclic triterpene, was identified in the CH2Cl2 fraction of CIE to attenuate LMP1-induced NF-κB activation and LCL viability. This study demonstrates that lupeol is one of active compounds in the CH2Cl2 fraction of CIE that inhibits LMP1-induced NF-κB activation and reduces NF-κB-dependent LCL viability.

Na[(18)F]F PET/CT is a promising hot-spot imaging modality for MI.

Positron emission tomography (PET)/computed tomography (CT) using sodium [18F]fluoride (Na[18F]F) has been proven to be a promising hot-spot imaging modality for myocardial infarction (MI). We investigated Na[18F]F uptake in ischemia–reperfusion injury (IRI) of rats and humans. Sodium [18F]fluoride PET/CT was performed in Sprague-Dawley rats that had IRI surgery, and it readily demonstrated prominent Na[18F]F uptake in the infarct area post-IRI. Sodium [18F]fluoride uptake was matched with negative 2,3,5-triphenyl-2H-tetrazolium chloride staining results, accompanied by myocardial apoptosis and associated with positive calcium staining results. Furthermore, area at risk was negative for Na[18F]F uptake. Cyclosporine A (CysA) treatment reduced standardized uptake value of 18F over the infarct area, and a significant decrease in infarct size was also observed by the CysA treatment. In humans, Na[18F]F PET/CT readily demonstrated increased Na[18F]F uptake in the 2 patients with MI post-percutaneous coronary intervention. In conclusion, this study sheds light on the potential utility of Na[18F]F PET/CT as a hot-spot imaging modality for myocardial IRI.

A proof-of-concept study is presented using dual gene therapy that employed a small hairpin RNA (shRNA) specific for mammalian target of rapamycin (mTOR) and a herpes simplex virus-thymidine kinase (HSV-TK) gene to inhibit the growth of tumors. Recombinant adeno-associated virus (rAAV) vectors containing a mutant TK gene (sc39TK) were transduced into HeLa cells, and the prodrug ganciclovir (GCV) was administered to establish a suicide gene-therapy strategy. Additionally, rAAV vectors expressing an mTOR-targeted shRNA were employed to suppress mTOR-dependent tumor growth. GCV selectively induced death in tumor cells expressing TK, and the mTOR-targeted shRNA altered the cell cycle to impair tumor growth. Combining the TK-GCV system with mTOR inhibition suppressed tumor growth to a greater extent than that achieved with either treatment alone. Furthermore, HSV-TK expression and mTOR inhibition did not mutually interfere with each other. In conclusion, gene therapy that combines the TK-GCV system and mTOR inhibition shows promise as a novel strategy for cancer therapy.