Aquaporin (AQP) 3, which is predominantly expressed in the colon, is considered to play an important role in regulating the fecal water content in the colon. In this study, the role of AQP3 in the colon was examined using HgCl(2) and CuSO(4), which are known to inhibit AQP3 function. The fecal water content was measured up to 1 h after the rectal administration of HgCl(2) or CuSO(4) to rats. The results showed that the fecal water content in the HgCl(2) administration group increased significantly to approximately 4 times that in the control group, and severe diarrhea was observed. However, no changes were observed in the mRNA expression level of the osmoregulatory genes (sodium myo-inositol transporter and taurine transporter) and the level and distribution of AQP3 protein expression, as determined 1 h after the administration of HgCl(2). Comparable results were observed in the CuSO(4) administration group. The results of this study indicated that the inhibition of AQP3 function in the colon caused diarrhea. Therefore, it has been revealed that the fecal water content in the colon is controlled by the transport of water from the luminal side to the vascular side, which is mediated by AQP3. Our findings suggest that a drug that modulates the function or expression of AQP3 in the colon may represent a new target for the development of laxatives.

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We previously showed that ergosterol has an inhibitory effect on bladder carcinogenesis. In this study, we aimed to elucidate the molecular mechanism by which ergosterol inhibits bladder carcinogenesis using a rat model of N-butyl-N-(4-hydroxybutyl)nitrosamine-induced bladder cancer. The messenger ribonucleic acid (mRNA) expression level of the cell cycle-related gene cyclin D1 and inflammation-related gene cyclooxygenase-2 in bladder epithelial cells was significantly increased in the carcinogenesis group compared with the control group. In contrast, in ergosterol-treated rats, these increases were significantly suppressed. Ergosterol did not affect the plasma testosterone concentration or the binding of dihydrotestosterone to androgen receptor (AR). The mRNA expression levels of 5α-reductase type 2 and AR were higher in the carcinogenesis group than in the control group but were significantly decreased by ergosterol administration. These results suggest that ergosterol inhibits bladder carcinogenesis by modulating various aspects of the cell cycle, inflammation-related signaling, and androgen signaling. Future clinical application of the preventive effect of ergosterol on bladder carcinogenesis is expected.

The ocular histopathological and ultrastructural features of fucosidosis in a man who survived to the age of 25 years are reported. Virtually all of the cells of the eye contained cytoplasmic, membrane-bound, and confluent areas of fibrillogranular and multilaminated material. The most striking accumulations were present within the endothelial cells lining blood vessels and corneal endothelium, and the least amount was present in the uveal melanocytes.

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We have previously shown that menthol attenuates the anticoagulant effect of warfarin by increasing the expression levels of CYP3A and CYP2C in the liver. This study evaluated the effects of menthol on the pharmacokinetics of the CYP3A substrate triazolam and the CYP2C substrate phenytoin. Menthol was orally administered to mice for 7 d. Twenty-four hours after the administration of menthol, triazolam was orally administered, and the plasma concentration was measured. In addition, the CYP3A metabolic activity for triazolam and the CYP3A expression level in the liver were determined. The effects of menthol on the pharmacokinetics of phenytoin were assessed in the same manner. In the menthol-treated group, the area under the blood concentration-time curve (AUC) of triazolam was lower and its clearance was higher compared with the control group. The CYP3A metabolic activity and CYP3A expression level in the liver were significantly increased in the menthol-treated group compared with the control group. Similarly, the AUC of phenytoin was lower and the hepatic CYP2C expression level was higher in the menthol-treated group. Thus, menthol lowered the plasma concentrations of triazolam and phenytoin when concurrently administered. These effects may be attributed to an increased metabolic activity for these drugs due to the increased expression of CYP3A and CYP2C in the liver.

Aim We previously clarified that the herbal medicine Polyporus Sclerotium, a constituent of Choreito, has an inhibitory effect on bladder carcinogenesis and that ergosterol is the active ingredient. In addition, we showed that this action of ergosterol may be caused by the metabolite brassicasterol. Here, we aimed to elucidate the detailed molecular mechanism by which brassicasterol inhibits bladder carcinogenesis. Methods A rat model of bladder cancer was established by feeding rats N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine (BHBN) and sodium saccharin (SS). After intraperitoneal administration of brassicasterol to rats, the mRNA expression levels of cell cycle‐related genes (cyclin D1, c‐fos, and c‐jun), inflammation‐related genes (cyclooxygenase‐2; COX‐2), and androgen signal‐related genes (5α‐reductase type 1; 5α‐R1, 5α‐reductase type 2; 5α‐R2, and the androgen receptor; AR) in bladder epithelial cells were analyzed. Results Brassicasterol significantly suppressed bladder carcinogenesis induced by BHBN and SS. The mRNA expression levels of cyclin D1 in bladder epithelial cells were significantly higher in the carcinogenesis group than in the control group. Additionally, the expression levels of c‐fos and c‐jun, constituents of the transcription factor activator protein‐1 (AP‐1) upstream of cyclin D1, were significantly increased in the carcinogenesis group compared with the control group. Moreover, the expression levels of COX‐2, 5α‐R1, 5α‐R2, and AR were significantly higher in the carcinogenesis group. In contrast, in rats treated with brassicasterol, the increases in the expression levels of these molecules were significantly suppressed. Conclusion We clarified that brassicasterol suppresses bladder carcinogenesis by acting on cell cycle‐related signaling, inflammation‐related signaling, and androgen signaling via multiple mechanisms.