Carnosol induces apoptotic cell death through ROS-dependent inactivation of STAT3 in human melanoma G361 cells

Melanoma is the leading cause of skin cancer deaths, and the poor prognosis of metastatic melanoma has made needs for a novel pharmacological treatment or efficient intervention. Carnosol, a major polyphenolic compound from Rosmarinus officinalis, has a wide range of biological activities including anti-cancer effect. However, the underlying molecular mechanisms of its anti-cancer effect remain poorly understood in malignant human melanoma cells. In the present study, we investigate the apoptotic effect and the underlying anti-cancer mechanisms of carnosol. Our results revealed that carnosol strongly induced apoptosis against human melanoma G361 cells in a dose- and time-dependent manner, and caused dramatical elevation in cellular reactive oxygen species (ROS) level during apoptosis. In mechanistic studies, carnosol treatment decreased protein level of anti-apoptotic B‑cell lymphoma 2 (Bcl-2) and B cell lymphoma-extra large (Bcl-xL), however, increased level of pro-apoptotic Bcl-2-associated X protein (Bax) protein. Moreover, carnosol escalated cellular level of p53, which was accompanied by a decline of mouse double minute 2 homolog (MDM2) level. Also, carnosol inhibited activation of Src and signal transducer and activator of transcription 3 (STAT3), therefore down-regulated STAT3-dependent gene expression, such as D-series cyclin and survivin. These changes by carnosol were attenuated by pre-treatment of N-acetyl cysteine, and abolished progression of carnosol-induced apoptosis. In conclusion, carnosol induced apoptosis in human melanoma G361 cells through ROS generation and inhibition of STAT3-mediated pathway. Our results provide molecular bases of carnosol-induced apoptosis, and suggest a novel candidate for human melanoma treatment.This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2018R1D1A1A02050495, J.-S. Choi) and by the Ministry of Science, ICT and Future Planning 2017R1A2B4009831, K.- S. Chun)

miRNA regulation of cytotoxic effects in mouse Sertoli cells exposed to nonylphenol

Background: It is known that some environmental chemicals affect the human endocrine system. The harmful effects of endocrine disrupting chemical (EDC) nonylphenol (NP) have been studied since the 1980s. It is known that NP adversely affects physiological functions by mimicking the natural hormone 17 beta-estradiol. In the present study, we analyzed the expression of miRNAs and their target genes in mouse Sertoli TM4 cells to better understand the regulatory roles of miRNAs on Sertoli cells after NP exposure. Methods: Mouse TM4 Sertoli cells were treated with NP for 3 or 24 h, and global gene and miRNA expression were analyzed using Agilent mouse whole genome and mouse miRNA v13 arrays. Results: We identified genes that were > 2-fold differentially expressed in NP-treated cells and control cells (P < 0.05) and analyzed their functions through Gene Ontology analysis. We also identified miRNAs that were differentially expressed in NP-treated and control cells. Of the 186 miRNAs the expression of which differed between NP-treated and control cells, 59 and 147 miRNAs exhibited 1.3-fold increased or decreased expression at 3 and 24 h, respectively. Network analysis of deregulated miRNAs suggested that Ppara may regulate the expression of certain miRNAs, including miR-378, miR-125a-3p miR-20a, miR-203, and miR-101a, after exposure to NP. Additionally, comprehensive analysis of predicted target genes for miRNAs showed that the expression of genes with roles in cell proliferation, the cell cycle, and cell death were regulated by miRNA in NP-treated TM4 cells. Levels of expression of the miRNAs miR-135a* and miR-199a-5p were validated by qRT-PCR. Finally, miR-135a* target gene analysis suggests that the generation of reactive oxygen species (ROS) following exposure to NP exposure may be mediated by miR-135a* through regulation of the Wnt/beta-catenin signaling pathway. Conclusions: Collectively, these data help to determine NP's actions on mouse TM4 Sertoli cells and increase our understanding of the molecular mechanisms underlying the adverse effects of xenoestrogens on the reproductive system.This work was supported an Eco-Technopia 21 project grant from the Ministry of Environment (Development of Decision Method of Chromosomal Abnormality in Reproductive System by Toxic Substances at the Korea Institute of Toxicology)

Self-care use patterns in the UK, US, Australia, and Japan: a multinational web-based survey

AbstractBackgroundThe trend toward patient- or consumer-centered healthcare has been accelerated by advances in technology, consumer empowerment, and a shift from infectious to chronic diseases. The purpose of this study was to examine the growing self-care market by analyzing self-care patterns.MethodsWe conducted a cross-sectional, web-based survey involving adults from nine major cities in the UK, the USA, Australia, and Japan. This study examined the extent and frequency of self-care, self-care expenditure, sources of self-care information, and reasons for self-care in each country.ResultsThe results showed that the prevalence of self-care was highest in Japan (54.9%), followed by the UK (43.1%), the USA (42.5%), and Australia (40.4%). The primary reason for practicing self-care was “to manage my healthcare myself” (cited by 45.7%, 59.5%, 49.2%, and 4.1% of participants in Australia, Japan, the UK, and the USA, respectively). Significant linear associations were observed between age and the prevalence of self-care in all countries (p<0.05), indicating that self-care prevalence decreased with age in the UK, the USA, and Australia, and increased with age in Japan. The frequency with which self-care was practiced was positively correlated with age in the USA (p<0.05), Australia (p<0.01), and Japan (p<0.05). In addition to acquaintances, internet search engines and information obtained from pharmacies were considered reliable and widely used sources of self-care information.ConclusionWhen developing self-care products or services, healthcare providers and policymakers should consider self-care patterns

In-situ fabrication of cobalt-doped SrFe2As2 thin films by using pulsed laser deposition with excimer laser

The remarkably high superconducting transition temperature and upper critical field of iron(Fe)-based layered superconductors, despite ferromagnetic material base, open the prospect for superconducting electronics. However, success in superconducting electronics has been limited because of difficulties in fabricating high-quality thin films. We report the growth of high-quality c-axis-oriented cobalt(Co)-doped SrFe2As2 thin films with bulk superconductivity by using an in-situ pulsed laser deposition technique with a 248-nm-wavelength KrF excimer laser and an arsenic(As)-rich phase target. The temperature and field dependences of the magnetization showing strong diamagnetism and transport critical current density with superior Jc-H performance are reported. These results provide necessary information for practical applications of Fe-based superconductors.Comment: 8 pages, 3figures. to be published at Appl. Phys. Let

ヒガシアジア ケイザイ キョウドウタイ ノ スイシン ホウコウ ト カダイ

訳: 金, 美善 / Translated by Kim, Mi Seo

Potassium chloride elicits enhancement of bilobalide and Ginkgolides production by Ginkgo biloba cell cultures

This study investigated the ability of potassium chloride (KCl) to elicit the production of bilobalide (BB), ginkgolide A (GA) and ginkgolide B (GB) by Ginkgo biloba cell suspension cultures. The salt stress by KCl treatments increased production of BB, GA and GB in both suspended cells and cultured medium. Especially, treatment of KCl 800 mM of highest concentration was stimulated emission into cultured medium BB, GA and GB compounds accumulated in cells. Although KCl 800 mM severely inhibited cells growth, the maximum content of GA and GB in cells was obtained in the treatment of KCl 800 mM, which was 1.9 and 4.0 times higher than the control. These results thus suggest that salt stress can afford enhanced production of secondary metabolites by plant cell cultures

Radiofrequency Ablation of Liver Cancer: Early Evaluation of Therapeutic Response with Contrast-Enhanced Ultrasonography

The early assessment of the therapeutic response after percutaneous radiofrequency (RF) ablation is important, in order to correctly decide whether further treatment is necessary. The residual unablated tumor is usually depicted on contrast-enhanced multiphase helical computed tomography (CT) as a focal enhancing structure during the arterial and portal venous phases. Contrast-enhanced color Doppler and power Doppler ultrasonography (US) have also been used to detect residual tumors. Contrast-enhanced gray-scale US, using a harmonic technology which has recently been introduced, allows for the detection of residual tumors after ablation, without any of the blooming or motion artifacts usually seen on contrast-enhanced color or power Doppler US. Based on our experience and reports in the literature, we consider that contrast-enhanced gray-scale harmonic US constitutes a reliable alternative to contrast-enhanced multiphase CT for the early evaluation of the therapeutic response to RF ablation for liver cancer. This technique was also useful in targeting any residual unablated tumors encountered during additional ablation