St. John’s Wort Regulates Proliferation and Apoptosis in MCF-7 Human Breast Cancer Cells by Inhibiting AMPK/mTOR and Activating the Mitochondrial Pathway

St. John’s Wort (SJW) has been used as an estrogen agonist in the systems affected by menopause. Also, hypericin, a bioactive compound of SJW, has been used as a photosensitizer in photodynamic therapy. In the present study, we investigate the anti-proliferative and pro-apoptotic effects of SJWto demonstrate the chemo-preventive effect in human breast cancer cells. MCF-7 cellswere culturedwith DMSO or various concentrations of SJWethanol extract (SJWE). Cell viability, proliferation, apoptosis, the expression of proteins involved in cell growth and apoptosis, and caspase-3/7 activity were examined. SJWE dose-dependently suppressed cell growth and induced apoptosis ofMCF-7 cells. Mechanistically, SJWE enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and decreased the expression of p-mammalian target of rapamycin (p-mTOR) and p-eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1). Also, SJWE inhibited the phosphorylation of protein kinase B (Akt) and showed increases in the expression of pro-apoptotic proteins Bax and Bad with decreases in the expression of anti-apoptotic proteins including B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), and p-Bcl-2-associated death promoter (p-Bad). SJWE at 50 µg/mL showed markedly enhanced caspase-7 activation. Taken together, our results provide evidence that SJWE shows anti-proliferative and pro-apoptotic effects via inhibition of AMPK/mTOR and activation of a mitochondrial pathway. Therefore, SJWE can be used as a chemo-preventive agent without photo-activation

ケータイのかくれた次元 : モバイル・メディアをめぐる解釈的メディア論

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 水越 伸, 東京大学准教授 山内 祐平, 東京大学准教授 北田 暁大, 関西大学教授 岡田 朋之, 静岡大学准教授 原 知章University of Tokyo(東京大学

Effects of Electroacupuncture on N-Methyl-D-aspartate Receptor-Related Signaling Pathway in the Spinal Cord of Normal Rats

This study examined the influence of the N-methyl-D-aspartate receptor (NMDAR) on the modulation of related spinal signaling after electroacupuncture (EA) treatment in normal rats. Bilateral 2 Hz EA stimulations (1-2-3.0 mA) were delivered at acupoints corresponding to Zusanli (ST36) and Sanyinjiao (SP6) in men for 30 min. Thermal sensitization was strongly inhibited by EA, but this analgesia was reduced by preintrathecal injection of the NMDAR antagonist, MK801. Phosphorylation of the NMDAR NR2B subunit, cAMP response element-binding protein (CREB), and especially phosphatidylinositol 3-kinase (PI3K) were significantly induced by EA. However, these marked phosphorylations were not observed in MK801-pretreated rats. EA analgesia was reduced by preintrathecal injection with the calcium chelators Quin2 and TMB8, similar to the results evident using MK801. Phosphorylation of PI3K and CREB induced by EA was also inhibited by TMB8. Calcium influx by NMDAR activation may play an important role in EA analgesia of normal rats through the modulation of the phosphorylation of spinal PI3K and CREB

Red pepper seed water extract inhibits preadipocyte differentiation and induces mature adipocyte apoptosis in 3T3-L1 cells

BACKGROUND/OBJECTIVES: Reducing the number of adipocytes by inducing apoptosis of mature adipocytes as well as suppressing differentiation of preadipocytes plays an important role in preventing obesity. This study examines the anti-adipogenic and pro-apoptotic effect of red pepper seed water extract (RPS) prepared at 4°C (RPS4) in 3T3-L1 cells. MATERIALS/METHODS: Effect of RPS4 or its fractions on lipid accumulation was determined in 3T3-L1 cells using oil red O (ORO) staining. The expressions of AMP-activated protein kinase (AMPK) and adipogenic associated proteins [peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding proteins α (C/EBP α), sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC)] were measured in 3T3-L1 cells treated with RPS4. Apoptosis and the expression of Akt and Bcl-2 family proteins [B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad), Bcl-2 like protein 4 (Bax), Bal-2 homologous antagonist/killer (Bak)] were measured in mature 3T3-L1 cells treated with RPS4. RESULTS: Treatment of RPS4 (0-75 ug/mL) or its fractions (0-50 ug/mL) for 24 h did not have an apparent cytotoxicity on pre and mature 3T3-L1 cells. RPS4 significantly suppressed differentiation and cellular lipid accumulation by increasing the phosphorylation of AMPK and reducing the expression of PPAR-γ, C/EBP α, SREBP-1c, FAS, and ACC. In addition, all fractions except ethyl acetate fraction significantly suppressed cellular lipid accumulation. RPS4 induced the apoptosis of mature adipocytes by hypophosphorylating Akt, increasing the expression of the pro-apoptotic proteins, Bak, Bax, and Bad, and reducing the expression of the anti-apoptotic proteins, Bcl-2 and p-Bad. CONCLUSIONS: These finding suggest that RPS4 can reduce the numbers as well as the size of adipocytes and might useful for preventing and treating obesity

Front Matter

This file contains cover for Volume II, Issue II, Editorial Board, Acknowledgements

Mediastinal lymphoma in a young Turkish Angora cat

An 8-month old intact male Turkish Angora cat was referred to the Veterinary Medical Teaching Hospital (VMTH), Seoul National University, for an evaluation of anorexia and severe dyspnea. The thoracic radiographs revealed significant pleural effusion. A cytology evaluation of the pleural fluid strongly suggested a lymphoma containing variable sized lymphocytes with frequent mitotic figures and prominent nucleoli. The feline leukemia virus and feline immunodeficiency virus tests were negative. The cat was euthanized at his owner's request and a necropsy was performed. A mass was detected on the mediastinum and lung lobes. A histopathology evaluation confirmed the mass to be a lymphoma. Immunohistochemistry revealed the mass to be CD3 positive. In conclusion, the cat was diagnosed as a T-cell mediastinal lymphoma

Low-Concentration Phosphate Removal Using Microwave-Assisted Granular Activated Carbon Modified by Magnesium

Objectives In this study, we propose a new method for preparing magnesium-modified granular activated carbon (Mg-GAC) using microwave irradiation. The objective is to identify the optimal factors for efficiently removing low-concentration phosphate using the Mg-GAC. Methods We impregnated Mg on activated carbon and modified Mg-GAC using microwave irradiation. Experiments were conducted with modification parameters such as impregnation time (1-12 hours), impregnation solution concentration (0.5-3 M), and microwave irradiation time (0-20 minutes). Factors affecting phosphate removal were set as pH (2-10) and reaction time (0-240 minutes), and were applied to kinetic models and isothermal adsorption models. Results and Discussion After modification, particle distribution on the adsorbent's surface and 40-time increase in percent composition of Mg showed that Mg effectively coated to the GAC surface. At initial concentration of 2 mg P/L, the optimal modification conditions were 1-M Mg impregnation solution concentration, 2-hr impregnation time, and 10-min microwave irradiation time. The optimal experimental conditions for low phosphate removal efficiency were pH 4 and 180-min adsorption time. The difference of maximum removal efficiency between Mg-GAC (91.9%) and GAC (63.6%) was 28.3%. Mg-GAC is suitable for both Langmuir and Freundlich isotherm models, and the reaction kinetics followed a pseudo-second-order model. The microwave irradiation time for Mg-GAC preparation was 10 min, and the energy consumption was 0.55 kWh/g, which showed that microwave irradiation is one of promising methods for modification of GAC by metal. Conclusion The Mg-GAC modified by magnesium and microwave irradiation enhanced removal efficiency for low-concentration phosphate compared with GAC

Multiple assessment methods of prenatal exposure to radio frequency radiation from telecommunication in the Mothers and Children’s Environmental Health (MOCEH) study

Objectives: To evaluate prenatal exposure to radiofrequency radiation (RFR) from telecommunication using a mobile phone questionnaire, operator data logs of mobile phone use and a personal exposure meter (PEM). Material and Methods: The study included 1228 mother–infants pairs from the Mothers and Children’s Environmental Health (MOCEH) study – a multicenter prospective cohort study ongoing since 2006, in which participants were enrolled at ≤ 20 weeks of pregnancy, with a follow-up of a child birth and growth to assess the association between prenatal environmental exposure and children’s health. The questionnaire included the average calling frequency per day and the average calling time per day. An EME Spy 100 PEM was used to measure RFR among 269 pregnant women from November 2007 to August 2010. The operators’ log data were obtained from 21 participants. The Spearman’s correlation test was performed to evaluate correlation coefficient and 95% confidence intervals between the mobile phone use information from the questionnaire, operators’ log data, and data recorded by the PEM. Results: The operators’ log data and information from the self-reported questionnaire showed significantly high correlations in the average calling frequency per day (ρ = 0.6, p = 0.004) and average calling time per day (ρ = 0.5, p = 0.02). The correlation between information on the mobile phone use in the self-reported questionnaire and exposure index recorded by the PEM was poor. But correlation between the information of the operators’ log data and exposure index for transmission of mobile communication was significantly high: correlation coefficient (p-value) was 0.44 (0.07) for calling frequency per day, and it was 0.49 (0.04) for calling time per day. Conclusions: The questionnaire information on the mobile phone use showed moderate to high quality. Using multiple methods for exposure assessment might be better than using only one method. Int J Occup Med Environ Health 2016;29(6):959–97