Chaperone protein BiP binds to Ire1 and dissociates in response to endoplasmic reticulum (ER) stress. However, it remains unclear how the signal transducer Ire1 senses ER stress and is subsequently activated. The crystal structure of the core stress-sensing region (CSSR) of yeast Ire1 luminal domain led to the controversial suggestion that the molecule can bind to unfolded proteins. We demonstrate that, upon ER stress, Ire1 clusters and actually interacts with unfolded proteins. Ire1 mutations that affect these phenomena reveal that Ire1 is activated via two steps, both of which are ER stress regulated, albeit in different ways. In the first step, BiP dissociation from Ire1 leads to its cluster formation. In the second step, direct interaction of unfolded proteins with the CSSR orients the cytosolic effector domains of clustered Ire1 molecules.

The effect of passion fruit, the fruit of Passiflora edulis , on melanin inhibition and collagen synthesis was studied using cultured human melanoma and fibroblast cells. Passion fruit was divided into three parts, rind (PF-R), pulp (PF-P), and seed (PF-S), and each part was extracted using 80% ethanol. The concentration of polyphenols was higher in PF-S than in PF-R or PF-P. Treatment of melanoma cells with PF-S led to inhibition of melanogenesis. In addition, the production of total soluble collagen was elevated in dermal fibroblast cells cultured in the presence of PF-S. PF-R and PF-P did not yield these effects. Furthermore, the removal of polyphenols from PF-S led to the abolishment of the effects described above. We discovered that piceatannol (3,4,3',5'-tetrahydroxy-trans-stilbene) is present in passion fruit seeds in large amounts and that this compound is the major component responsible for the PF-S effects observed on melanogenesis and collagen synthesis.

Piceatannol (trans-3,3',4,5'-tetrahydroxystilbene), a natural analogue of resveratrol, has multiple biological functions. Nevertheless, piceatannol's biological fate is yet to be determined. In this study, we evaluated the absorption and metabolism of piceatannol in rats. Furthermore, the area under the plasma concentration curves (AUC) and metabolic pathway of piceatannol were compared with those of resveratrol. We determined the plasma concentrations of piceatannol, resveratrol, and their respective metabolites following their intragastric administration. Resveratrol metabolites were only conjugates, whereas piceatannol metabolites were piceatannol conjugates, O-methyl piceatannol, and its conjugates. The AUC for piceatannol, resveratrol, and their metabolites increased in a dose-dependent manner (90-360 μmol/kg). The AUC for total piceatannol was less than that for total resveratrol, whereas the AUC for piceatannol (8.6 μmol·h/L) after piceatannol and resveratrol coadministration was 2.1 times greater than that for resveratrol (4.1 μmol·h/L). The greater AUC for piceatannol was a result of its higher metabolic stability.

With conventional MRI, a tendency of ADCs could be predicted. ADCs may not provide additional information, especially to discriminate benign from malignant lesions.

Piceatannol is present in passion fruit (Passiflora edulis) seeds in high amounts. In this study, we isolated the second major polyphenolic compound of passion fruit seeds and identified it as scirpusin B, which is a dimer of piceatannol. We investigated the antioxidant activities and vasorelaxing effects of these polyphenols. Their antioxidant effects were measured using an in vitro 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, and their vasorelaxant effects were determined ex vivo in rat thoracic aorta. Both polyphenolic compounds exhibited potent antioxidant activities and significant vasorelaxant effects in endothelium-intact aortas. More specifically, scirpusin B exerted a greater antioxidant activity and vasorelaxant effect compared with that of piceatannol. Additionally, the vasorelaxation effects of the compounds were induced via the NO derived from the endothelium. This study provides the possibility that polyphenols in passion fruit seeds are effective against cardiovascular diseases (CVDs).

Objective: Major depressive disorder (MDD) and adjustment disorder (AD) are common psychiatric disorders in cancer patients but are often overlooked in clinical oncology settings. We introduced a clinical screening program utilizing the Distress and Impact Thermometer (DIT) to identify MDD and AD in cancer outpatients receiving chemotherapy. This study assessed the usefulness of the screening program.Methods: Pharmacists administered the DIT to consecutive patients undergoing chemotherapy at an outpatient clinic. Psychiatric treatment was recommended to all the patients with positive screening results. The proportion of patients referred to the Psychiatric Service during the program period was then compared with that during a usual care period.Results: Of the 520 patients who started chemotherapy during the 6-month program period, 5.0% (26/520) were referred to the Psychiatric Service and 2.7% (15/520) were diagnosed as having MDD or AD. No statistically significant difference in the referral rates was observed between the two periods (2.7 vs 1.0%, p 5 0.46). However, the period from the first chemotherapy treatment until the visit to the Psychiatric Service was significantly shorter during the program period than during the period of usual care (12.9713.2 days vs 55.6717.6 days, po0.001).Conclusions: The proportion of patients referred to the Psychiatric Service for the treatment of MDD or AD during the program period was not different from that during the usual care period. However, the program was useful for introducing psychiatric treatment at an earlier stage. Further modifications to the program to improve the referral rate are necessary.

We previously found that passion fruit (Passiflora edulis) seeds contained a high amount of piceatannol (3,5,3′,4′-trans-tetrahydroxystilbene), a natural analog of resveratrol (3,5,4′-trans-trihydroxystilbene). Resveratrol has been proposed as a potential anti-metabolic disorder compound, by its activation of sirtuin and AMP-activated protein kinase. Many reports show that resveratrol ameliorates diet-induced obesity and insulin resistance. However, it is not known whether piceatannol also affects diet-induced obesity. We explored the effect of piceatannol on high fat diet-fed mice. The results showed that piceatannol did not affect high fat diet-induced body weight gain or visceral fat gain in mice. However, piceatannol did reduce fasting blood glucose levels. Furthermore, to explore the potential of passion fruit seed extract containing piceatannol as a functional food, passion fruit seed extract was administered in a genetic diabetic mouse model (db/db mice). Single administration of passion fruit seed extract, as well as piceatannol reduced the blood glucose levels of these db/db mice. These results suggest that piceatannol and passion fruit seed extract may have potential application in the prevention of diabetes.Key words piceatannol; passion fruit seed; antidiabetic activity; high fat diet; db/dbThe incidence of metabolic syndrome is increasing worldwide due to aging and changes in lifestyle. In particular, this increase is largely attributed to the rise in the prevalence of obesity, and this common metabolic disorder is associated with increased risk of cardiovascular diseases and type II diabetes, and the latter substantially decreases quality of life and increases health care costs. It is difficult to strictly control blood glucose levels over the long term, even though many anti-diabetic medications are clinically available. Therefore, the development of functional foods that can prevent or improve type II diabetes is an urgent matter.Resveratrol is a natural component of several plants, including grapes, berries, and peanuts. Resveratrol displays widespread functions and has several health-promoting effects owing to its anti-cancer, anti-inflammation, and antioxidant activity.1) Recently, resveratrol has been proposed as a potential anti-metabolic syndrome compound because of its role in activating sirtuin and AMP-activated protein kinase (AMPK).2-5) Indeed, several studies have shown that resveratrol protects mice against diet-induced obesity.6-8) Resveratrol has also been shown to have a favorable effect on glucose metabolism in humans.9,10) However, it should be noted that no weight loss has been reported after resveratrol treatment in any human study. 11)Piceatannol is a hydroxylated analog of resveratrol and is also found in various plants, including grapes and rhubarb. Although piceatannol shows activities similar to resveratrol, its levels in plants are significantly lower than those of resveratrol, 12) and it has therefore received far less research attention. We previously found that passion...

Piceatannol is a phytochemical that is present in large amounts in passion fruit (Passiflora edulis) seeds, and is an analog of resveratrol. Recently, the absorption and metabolism of piceatannol were investigated in rats, and isorhapontigenin, O-methyl piceatannol, was detected as a piceatannol metabolite in rat plasma. To elucidate the function of piceatannol and its metabolites, we investigated the expression of sirtuin 1 (SIRT1) in THP-1 monocytic cells after treatment with piceatannol and its metabolites, and compared their effects with those of resveratrol and its metabolites. Piceatannol and resveratrol upregulated the expression levels of SIRT1 mRNA and SIRT1 protein. An extract of passion fruit seeds, which contained high levels of piceatannol, also upregulated SIRT1 mRNA expression. As for the metabolites, isorhapontigenin upregulated SIRT1 mRNA expression, whereas resveratrol glucuronides and sulfate did not affect SIRT1 expression. These findings indicate that after intake of piceatannol, not only piceatannol itself, but also its metabolite, isorhapontigenin, contributed to the upregulation of SIRT1 expression.