Larval pufferfish protected by maternal tetrodotoxin

Marine pufferfish contain tetrodotoxin (TTX), an extremely potent neurotoxin. All species of the genus Takifugu accumulate TTX in the liver and ovaries, although the tissue(s) in which it is localized can differ among species. TTX is the major defense strategy the pufferfish appears to use against predators. TTX is also used as a male-attracting pheromone during spawning. Here we demonstrate an additional (and unexpected) use of maternal TTX in the early larval stages of the Takifugu pufferfish. Predation experiments demonstrated that juveniles of all the species of fish used as predators ingested pufferfish larvae, but spat them out promptly. Liquid Chromatography-Tandem Mass Spectrometry (LC-MSMS) analysis revealed that the pufferfish larvae contain a small quantity of TTX, which is not enough to be lethal to the predators. Immunohistochemical analysis with anti-TTX monoclonal antibody revealed that the TTX is primarily localized in the body surface of the larvae as a layer of protection. Our study showed the female parent of the Takifugu pufferfish vertically transfers TTX to the larvae through its accumulation in the ovaries, and subsequent localization on the body surface of the larvae

Dielectric and Sorption Responses of Hydrogen-Bonding Network of Amorphous C-60(OH)(12) and C-60(OH)(36)

Hydrophilic fullerene derivatives of C-60(OH)(12) (1) and C-60(OH)(36) (2) bearing different numbers of -OH groups formed amorphous solids of 1.x(H2O) (x = 5-10) and 2.x(H2O) (x = 15-22), respectively, according to the humidity. The thermally activated dynamic molecular motion of polar H2O was confirmed in the DSC and dielectric spectra. Three-dimensional O-H center dot center dot center dot O hydrogen-bonding networks in amorphous 1 and 2 produced extrinsic adsorption-desorption pores with a hydrophilic environment posed by -OH groups, where N-2, CO2, H-2, and CH4 gases vapors and polar H2O, MeOH, and EtOH molecules reversibly adsorbed into the networks. The molecular motion of polar H2O was directly observed in dielectric enhancement and protonic conductivity in three-dimensional O-H center dot center dot center dot O hydrogen-bonding networks. The Brunauer-Emmett-Teller (BET) specific surface areas of amorphous 1 and 2 were 315 and 351 m(2) g(-1), respectively, from the CO2 sorption isotherms. Reversible vapor sorption behaviors with structural changes of amorphous 1 and 2 were also confirmed for the polar H2O, MeOH, and EtOH

Thermoreversible Nanogel Shuttle between Ionic Liquid and Aqueous Phases

We describe a nanogel that can reversibly shuttle between a hydrophobic ionic liquid (IL) phase and an aqueous phase in response to temperature changes. A thermosensitive diblock copolymer, consisting of poly­(ethylene oxide) (PEO) as the first segment and a random copolymer of <i>N</i>-isopropylacrylamide (NIPAm) and <i>N</i>-acryloyloxysuccinimide (NAS) as the second segment, was prepared as a nanogel precursor using anionic ring-opening polymerization of EO followed by reversible addition–fragmentation chain-transfer (RAFT) polymerization of NIPAm and NAS. After the micellization of the diblock copolymer in an aqueous solution upon heating to temperatures higher than the lower critical solution temperature (LCST) of the second segment, a coupling reaction of the NAS group of the P­(NIPAm-<i>r</i>-NAS) core with ethylenediamine gave a nanogel with a well-solvated PEO corona. The nanogel exhibited contrasting thermosensitivities in the aqueous and IL phases. Dynamic light scattering measurements revealed that the nanogel exhibited LCST phase behavior (low-temperature-swollen/high-temperature-shrunken) in the aqueous phase and the opposite upper critical solution temperature (UCST) phase behavior (high-temperature-swollen/low-temperature-shrunken) in hydrophobic ILs. The nanogel favored the aqueous phase at low temperatures and the IL phase at high temperatures because of the solubility changes in the PEO corona. Upon increasing the temperature, the nanogel underwent a swollen-to-shrunken phase change in the aqueous phase, a transfer from the aqueous phase to the IL phase, and a shrunken-to-swollen phase change in the IL phase. These processes were thermally reversible, which made the round-trip shuttling of the nanogel between the aqueous and IL phases possible

A Phenylfurocoumarin Derivative Reverses ABCG2-Mediated Multidrug Resistance In Vitro and In Vivo

The ATP-binding cassette subfamily G member 2 (ABCG2) transporter is involved in the development of multidrug resistance in cancer patients. Many inhibitors of ABCG2 have been reported to enhance the chemosensitivity of cancer cells. However, none of these inhibitors are being used clinically. The aim of this study was to identify novel ABCG2 inhibitors by high-throughput screening of a chemical library. Among the 5812 compounds in the library, 23 compounds were selected in the first screening, using a fluorescent plate reader-based pheophorbide a (PhA) efflux assay. Thereafter, to validate these compounds, a flow cytometry-based PhA efflux assay was performed and 16 compounds were identified as potential inhibitors. A cytotoxic assay was then performed to assess the effect these 16 compounds had on ABCG2-mediated chemosensitivity. We found that the phenylfurocoumarin derivative (R)-9-(3,4-dimethoxyphenyl)-4-((3,3-dimethyloxiran-2-yl)methoxy)-7H-furo [3,2-g]chromen-7-one (PFC) significantly decreased the IC50 of SN-38 in HCT-116/BCRP colon cancer cells. In addition, PFC stimulated ABCG2-mediated ATP hydrolysis, suggesting that this compound interacts with the substrate-binding site of ABCG2. Furthermore, PFC reversed the resistance to irinotecan without causing toxicity in the ABCG2-overexpressing HCT-116/BCRP cell xenograft mouse model. In conclusion, PFC is a novel inhibitor of ABCG2 and has promise as a therapeutic to overcome ABCG2-mediated MDR, to improve the efficiency of cancer chemotherapy