Resveratrol induces apoptosis by directly targeting Ras-GTPase-activating protein SH3 domain-binding protein 1.

Resveratrol (trans-3,5,4'-truhydroxystilbene) possesses a strong anticancer activity exhibited as the induction of apoptosis through p53 activation. However, the molecular mechanism and direct target(s) of resveratrol-induced p53 activation remain elusive. Here, the Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) was identified as a potential target of resveratrol, and in vitro binding assay results using resveratrol-conjugated Sepharose 4B beads confirmed their direct binding. Depletion of G3BP1 significantly diminishes resveratrol-induced p53 expression and apoptosis. We also found that G3BP1 negatively regulates p53 expression by interacting with ubiquitin-specific protease 10 (USP10), a deubiquitinating enzyme of p53. Disruption of the interaction of p53 with USP10 by G3BP1 interference leads to the suppression of p53 deubiquitination. Resveratrol, on the other hand, directly binds to G3BP1 and prevents the G3BP1/USP10 interaction, resulting in enhanced USP10-mediated deubiquitination of p53, and consequently increased p53 expression. These findings disclose a novel mechanism of resveratrol-induced p53 activation and resveratrol-induced apoptosis by direct targeting of G3BP1.

The relationship between psychosocial problems including depression and behavioural trends among middle-aged menopausal women in a cohort study.

OBJECTIVE: We investigated the association of psychosocial problems, menopausal symptoms such as hot flushes, and trends of smoking and use of cosmetics in our previous study. In this follow-up study, we researched psychiatric disorders and psychosocial problems in menopausal women. METHODS: We designed a cohort study with 577 Japanese women aged 30-64 years. Subjects were selected randomly from among women who visited the department of gender-specific medicine at Tokyo Women's Medical University East Medical Center between June 2010 and September 2011. We analysed trends such as smoking, using cosmetics, and menopausal symptoms and their association with the first lifetime episode of severe depression and anxiety using structured clinical interviews for the DSM-IV (structured clinical interview for DSM-IV, outpatient version [SCID]), the Center for Epidemiological Studies Depression Scale (CES-D) and the State-Trait Anxiety Inventory (STAI). RESULTS: Significant associations were observed between hot flushes, smoking and the frequency of using cosmetics. Furthermore, the trends in cosmetic use and smoking affected not only psychosocial problems, but also physical problems. Younger women suffered from psychosocial problems more than twice the rate of post-menopausal women. Those who reported their first severe depression episode were also affected by severe anxiety disorders and physical problems. CONCLUSION: By self-checking the frequency of using cosmetics is up to date knowledge of psychosocial mood problems and improving women's quality of life.

The psychosocial influence to habit using make-up of women aged 40 to 59 years menopausal Japanese women.

We conducted a survey to elucidate the psychosocial influence of menopausal symptoms on the habit of using make-up. This study included 420 Japanese women (age, 40-59 years) who were examined for the first time in a specialized women's outpatient clinic of our institution from June 2010 to September 2011. Using the Menopause-Specific Quality of Life questionnaire (MENQOL), we analysed the scores in relation to menopausal symptoms and whether and how frequently the subject used make-up (including foundation, lip rouge and eyebrow brushing). JMP version 9.0 software was used to statistically analyse the data. Significant results were observed for psychosocial symptoms (P = 0.0002) but not for vasomotor symptoms. Psychosocial symptoms tended to be more severe in women with climacteric <5 years previously. Furthermore, the frequency of make-up use was positively correlated with menopausal symptoms (P = 0.0251). There were strong relationships between psychological symptoms and make-up use in menopausal women. Psychological condition and the frequency of make-up use were inversely correlated, especially in women with climacteric <5 years previously.

Comparison of the symptoms of menopause and symptoms of thyroid disease in Japanese women aged 35-59 years.

OBJECTIVE: In this study, we surveyed thyroid function abnormalities and menopausal symptoms in young as well as in menopausal women. METHODS: We conducted a random survey among outpatients at our facility from September 2008 to June 2011. The study included 853 women aged 35-59 years. We assessed the subjects according to the Simplified Menopause Index, menstrual status, thyroid hormone measurements (thyroid stimulating hormone, free thyroxine, free triiodothyronine), the presence of Hashimoto's disease antibodies (anti-thyroid peroxidase antibody or anti-thyroglobulin antibody), the presence of Grave's disease (anti-TSH receptor antibody), markers of thyroid tumor (high thyroglobulin), and thyroid ultrasonography studies. The data were analyzed by means of the statistical program JMP version 8.0. RESULTS: 'Facial flushing', 'sweating', and 'thyroid tumor' were all positively related with age and menstrual status. 'Breathlessness and palpitations' were positively related to Grave's disease. Moreover, 'sweating', 'irritability', and 'stiff shoulders, low back pain, and joint pain' were related to thyroid tumors. 'Insomnia' decreased with age. Patients with Hashimoto's disease were very rare because they were usually treated at other hospitals that specialize in thyroid disease. CONCLUSION: The symptoms of thyroid function abnormalities were shown to be very similar to menopausal symptoms and were found to occur in younger women before the onset of menopause. This study shows the need to differentiate menopausal symptoms from those of thyroid diseases.

A study of menopausal symptoms in relation to habits of smoking and make-up using in Japanese women aged 35-59.

We conducted a survey to elucidate the influence with menopause symptoms and the impact of not only smoking but also using make-up among for Japanese women, included ages above and below the menopausal generation. The subjects of this study were 335 Japanese women from 35 to 59 years of age who were examined for the first time in the specialized women's outpatient clinic of our institution from July 2010 to June 2011 for 1 year period. We used the items of the Menopause-Specific Quality of Life Questionnaire. Similarly, we analysed the scores in relation to menopausal symptoms and whether the subject smoked, whether the subject used make-up depend on women (including foundation, lip rouge, brush one's eyebrows), how frequently she used make-up. The JMP version 9.0 software program was used to statistically analyse the score data. Significant associations were observed in psychosocial (P = 0.0196), tended to be more severe in women before menopause and after climacteric. Furthermore, the frequency of using make-up were negative relations with menopause symptoms (P = 0.0251) after climacteric. Smoking had made worse for physical symptoms (P < 0.001). Menopause symptoms are already experienced by younger women, especially, psychological symptoms. Also, physical conditions were influenced by smoking. Using make-up frequently was often seen after climacteric because of appearance changes by oestrogen dynamic decline.

Enantiomer separation by gas and high-performance liquid chromatography with tripeptide derivatives as chiral stationary phases.

Excellent enantiomer separation of a variety of racemic compounds, including alcohols, amines, amino alcohols, carboxylic acids, hydroxy acids and amino acids, was achieved by GC and HPLC with tripeptide derivatives, containing L-valyl-L-valyl-L-valine isopropyl ester as a chiral selector, bonded to amino silicone oil (CSP-3) and N-(2-aminoethyl)-3-aminopropyl silica gel (CSP-4) via a triazine ring, respectively. These results show that the hydrogen bonding association between solutes and chiral stationary phases (CSPs) can play an important role in chiral recognition in both GC and HPLC. The joint use of two CSPs is promising for the direct separation of racemic compounds.

Determination of felodipine and its metabolites in plasma using capillary gas chromatography with electron-capture detection and their identification by gas chromatography-mass spectrometry.

A novel method for the determination of felodipine and its metabolites in plasma by capillary gas chromatography (GC) with electron capture detection was developed. Felodipine and its oxidized metabolite were assayed by capillary GC after solid-phase extraction with the aid of a cool on-column injection technique. Acid metabolites, methyl monoacid and ethyl monoacid and diacid, were extracted with diethyl ether and propylated with 1-n-propyl-3-p-tolyltriazene before being submitted to capillary GC. These methods were very sensitive and useful for the pharmacokinetic study of felodipine. Felodipine and its metabolites were identified by GC-mass spectrometry. The mass spectral patterns of the peaks of extracts from human plasma samples after oral administration of felodipine were in good agreement with those of reference compounds.

Relationship between the structures of fatty acid amide derivatives and their antimicrobial activities.

The structure-activity relationships of derivatives of the antibiotic cerulenin were investigated by chemically modifying dodecanoic acid, its skeletal back-bone. The dimethylamide derivatives were active against both gram-positive and -negative bacteria, and fungi. Among the compounds having modified groups at positions C2 and C4, the most active were those with a carbonyl group at C4 and a double bond at C2. The dimethylamide and pyrrolidine amide derivatives of this structure type were the most active. Activity against bacteria and yeast increased with the number of carbon atoms in the skeleton, with the maximum activity being observed at C=12. No significant differences in activity against fungi were observed with change in chain length.