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A drug-eluting stent (DES) is one of the commonly used treatment techniques in percutaneous coronary intervention (PCI). Sirolimus (SRL) has been widely used for DES as a drug for suppressing neointimal hyperplasia causing restenosis. Phytoncides (PTC) are compounds released from trees and plants, and their solutions contain monoterpenoids such as α-pinene, careen, and myrceen. Some studies have reported that these components exhibit antioxidant, antimicrobial, and anti-inflammatory activities. We hypothesized that PTC may become an alternative drug to SRL for DES, exhibiting alleviated side effects as compared to SRL. A PTC-incorporated stent was compared with an SRL-incorporated stent in terms of physicochemical, pharmacokinetic, and biological properties. In in vitro studies, the effects of each drug on cells were investigated. The results showed that both drugs exhibited similar cytotoxicity, anti-inflammation, and antiproliferation effects. However, these effects resulted from different mechanisms associated with cells, as seen in the immunofluorescence result. An in vivo assay showed that the lumen area was significantly larger and the neointimal area was significantly smaller in SRL- and PTC-loaded stents compared to a drug-unloaded stent. These results suggest that phytoncide can be a feasible alternative drug to SRL for advanced DES although more studies are needed.

Several Fusarium species produce the polyketide mycotoxin zearalenone (ZEA), a causative agent of hyperestrogenic syndrome in animals that is often found in F. graminearum-infected cereals in temperate regions. The ZEA biosynthetic cluster genes PKS4, PKS13, ZEB1 and ZEB2 encode a reducing polyketide synthase, a non-reducing polyketide synthase, an isoamyl alcohol oxidase and a transcription factor respectively. In this study, the production of two isoforms (ZEB2L and ZEB2S) from the ZEB2 gene in F. graminearum via an alternative promoter was characterized. ZEB2L contains a basic leucine zipper (bZIP) DNA-binding domain at the N-terminus, whereas ZEB2S is an N-terminally truncated form of ZEB2L that lacks the bZIP domain. Interestingly, ZEA triggers the induction of both ZEB2L and ZEB2S transcription. ZEB2L and ZEB2S interact with each other to form a heterodimer that regulates ZEA production by reducing the binding affinity of ZEB2L for the ZEB2L gene promoter. Our study provides insight into the autoregulation of ZEB2 expression by alternative promoter usage and a feedback loop during ZEA production; this regulatory mechanism is similar to that observed in higher eukaryotes.