β-Secretase (BACE-1) inhibitory effect of biflavonoids

Here, we describe amentoflavone-type biflavonoids, which were isolated from natural sources and were found to inhibit β-secretase (BACE-1). The structure–activity relationship was studied, and compounds 1–8, 10, 17, and 18 showed BACE-1 inhibitory activity. Among these compounds, 2,3-dihydroamentoflavone 17 and 2,3-dihydro-6-methylginkgetin 18 exhibited potent inhibitory effects with IC₅₀ values of 0.75 and 0.35 μM, respectively.     

Delivery of sphingosine 1-phosphate from poly(ethylene glycol) hydrogels

While protein growth factors promote therapeutic angiogenesis, delivery of lipid factors such as sphingosine 1-phosphate (S1P) may provide better stabilization of newly formed vessels. We developed a biomaterial for the controlled delivery of S1P, a bioactive lipid released from activated platelets. Multiarm poly(ethylene glycol)-vinyl sulfone was cross-linked with albumin, a lipid-transporting protein, to form hydrogels. The rate of S1P release from the materials followed Fickian kinetics and was dependent upon the presence of lipid carriers in the release solution. Delivery of S1P from RGD-modified hydrogels increased the cell migration speed of endothelial cells growing on the materials. The materials also induced angiogenesis in the chorioallantoic membrane assay. Our data demonstrate that the storage and release of lipid factors provides a new route for the induction of angiogenesis by artificial materials.     

Synthesis of pyrrole-imidazole polyamide oligomers based on a copper-catalyzed cross-coupling strategy

Pyrrole-imidazole (Py-Im) polyamides are useful tools for chemical biology and medicinal chemistry studies due to their unique binding properties to the minor groove of DNA. We developed a novel method of synthesizing Py-Im polyamide oligomers based on a Cu-catalyzed cross-coupling strategy. All four patterns of dimer fragments could be synthesized using a Cu-catalyzed Ullmann-type cross-coupling with easily prepared monomer units. Moreover, we demonstrated that pyrrole dimer, trimer, and tetramer building blocks for Py-Im polyamide synthesis were accessible by combining site selective iodination of the pyrrole/pyrrole coupling adduct.     

Relationship between trace metal concentration and antioxidative activity of ancient rice bran (red and black rice) and a present-day rice bran (Koshihikari).

Antioxidative activity and polyphenol and trace metal content in bran from ancient rice varieties (red and black rice) and a present-day variety of rice (Koshihikari) were measured. The antioxidative properties of rice bran in terms of scavenging and quenching activity for reactive oxygen species (ROS), including superoxide anion radicals (*O(2)(-)), hydroxyl radicals (*OH), singlet oxygen ((1)O(2)) and lipid peroxide (LOO*), correlated well with polyphenol and trace metal content. In particular, the possibly that Mn content greatly contributes to the antioxidative properties of rice bran was revealed.     

Head-to-tail macrocyclization of cysteine-free peptides using an o-aminoanilide linker

A head-to-tail macrocyclization protocol for the preparation of cysteine-free cyclic peptides was investigated. The o-aminoanilide linker constructed in the peptide sequence by a standard Fmoc-based peptide synthesis procedure was subjected to nitrite-mediated activation under acidic conditions toward N-acyl benzotriazole as the active ester species. The subsequent cyclization smoothly proceeded by neutralization in the presence of additives such as 1-hydroxybenzotriazole (HOBt) and 1-hydroxy-7-azabenzotriazole (HOAt) to afford the expected cyclic pentapeptide, a CXCR4 antagonist. The cyclization efficiencies were dependent on the precursor open-chain sequence. The application of this step-wise activation-cyclization protocol to microflow reaction systems is also described.     

Amino Acid Sequences of Glycopeptides from Cucumisin

Oxidation of short-chain iso-alkanes (isobutane, isopentane, 2-methylpentane, and 3-methylpentane) was studied with propane-grown resting mycelia of Scedosporium sp. A-4. Isobutane was oxidized to terf-butanol, but both isobutane and tert-butanol were not used for growth. Isopentane was oxidized to 3-methyl-1-butanol, 2-methyl-2-butanol, and 3-methyl-2-butanol but not to 2-methyl-1-butanol. 2-Methylpentane was oxidized to 4-methyl-1-pentanol, 2-methyl-2-pentanol, and 4-methyl-2-pentanol but not to 2-methyl-1-pentanol or 2-methyl-3-pentanol. 3-Methylpentane was not oxidized. Oxidation of branched alcohols was also studied.     

Systemic administration of IL-23 induces potent antitumor immunity primarily mediated through Th1-type response in association with the endogenously expressed IL-12

IL-23, a cytokine, which is composed of the p40 subunit shared with IL-12 and the IL-23-specific p19 subunit, has been shown to preferentially act on Th1 effector/memory CD4+ T cells and to induce their proliferation and IFN-gamma production. The IL-23 is also reported to act on Th17-CD4+ T cells, which are involved in inducing tissue injury. In this study, we examined the antitumor effects associated with systemic administration of IL-23 and their mechanisms in mouse tumor system. Systemic administration of high-dose IL-23 was achieved using in vivo electroporation of IL-23 plasmid DNA into the pretibial muscles of C57BL/6 mice. The IL-23 treatment was associated with significant suppression of the growth of pre-existing MCA205 fibrosarcoma and prolongation of the survival of treated mice without significant toxicity when compared with those of the mice treated with EGFP. Although the therapeutic outcomes were similar to those with the IL-12 treatment, the IL-23 treatment induced characteristic immune responses distinctive to those of IL-12 treatment. The IL-23 administration even at the therapeutic levels did not induce detectable IFN-gamma concentration in the serum. In vivo depletion of CD4+ T cells, CD8+ T cells, or NK cells significantly inhibited the antitumor effects of IL-23. Furthermore, the CD4+ T cells in the lymph nodes in the IL-23-treated mice showed significant IFN-gamma and IL-17 response upon anti-CD3 mAb stimulation in vitro. These results and the ones in the IFN-gamma or IL-12 gene knockout mice suggest that potent antitumor effects of IL-23 treatment could be achieved when the Th1-type response is fully promoted in the presence of endogenously expressed IL-12.     

<Emphasis Type="Italic">Cacopsylla biwa</Emphasis> sp. nov. (Hemiptera: Psyllidae): a new pest of loquat <Emphasis Type="Italic">Eriobotrya japonica</Emphasis> (Rosaceae) in Japan

A new psyllid species, Cacopsylla biwa Inoue, sp. nov., is described from Tokushima Prefecture, Shikoku, Japan. This new species develops only on Eriobotrya japonica (Thunb.) Lindl. (Rosaceae), causing severe damage to its fruits and flowers. It is strongly suspected that C. biwa is an alien species. Morphological similarities and host-plant relationships indicate that C. biwa is most closely related to Cacopsylla eriobotryae (Yang) comb. nov. (transferred from Edentatipsylla Li), which occurs in Taiwan and feeds on Eriobotrya deflexa (Hemsl.) Nakai. Morphological diagnostic characteristics of C. biwa and differences from the other congeners are discussed. Information is provided on the biology and life cycle of the new species.     

Detection of Picomole Levels in Lipid Hydroperoxides by a Chemiluminescence Assay

A highly sensitive and simple chemiluminescent method for the quantitation of lipid hydroperoxides at the picomole level is described. The method is based on detecting the chemiluminescence generated during the oxidation of luminol by the reaction with hydroperoxide and cytochrome c under mild conditions. A semilogarithmic relationship was observed between the hydroperoxide added and the chemiluminescence produced. For lipid hydroperoxides, cytochrome c was a most favorable catalyst for generating the chemiluminescence, rather than cytochrome c heme peptide and horseradish peroxidase. This method had high sensitivity to methyl linoleate hydroperoxide, arachidonic acid hydroperoxide and cholesterol hydroperoxide, but low to /-butyl hydroperoxide, J-butyl perbenzoate, diacyl peroxides (lauroyl peroxode and benzoyl peroxide) and dialkyl peroxides (di-/-butyl peroxide and dicumyl peroxide).