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)

EFFECT OF SEAT TUBE ANGLE ON THE WORK EFFICIENCY OF LOWER LIMB MUSCLES DURING CYCLING

The effect of seat tube angle (STA) on work efficiency at lower limb muscle was evaluated during a pedal rotation using inverse dynamic model. Since the target is not professional cyclist, the various seat tube angles of 78, 68, 58 and 48 degrees was investigated. Cycling simulation was performed at 250W and 60rpm. The works of individual muscle of lower limb and the total work was estimated. The result shows that the total work of single leg at seat tube angles of 78, 68, 58 and 48 degrees were 168.1(J), 167.9(J), 168.9(J) and 170.8(J) respectively. In conclusion, the exertion of lower limb for delivering same amount of work to the crank is the smallest at around 72 degree of seat tube angle which mean work efficiency of lower limb is the greates

MOLECULAR DYNAMICS SIMULATION OF WATER BEHAVIOR AS A FUNCTION OF TEMPERATURES AND MONOMER NUMBERS IN NAFION 117

ABSTRACT The proton exchange membrane plays a critical role as an electrolyte for proton transports in the PEMFC. Generally, the membrane, such as Nafion 117, consists of a polytetrafluoroethylene (PTFE) backbone and side-chains terminated with a sulfonate group ( 3 SO − ). Operating the fuel cell, the membrane preferentially becomes hydrated by absorbing water. Then, the hydrogen atom on the 3 SO − part of the side-chain can detach from its own position and hop to the next 3 SO − site. The water management is the key to the efficient operation of the fuel cell, since the water content is the one of decisive factors for membrane's lifetime and efficient operations of fuel cells as well. In this report, we set up the molecular model for hydrated Nafion 117 and simulate the molecular movements for various temperatures and monomer numbers. Here, we obtain the mean square displacements of water molecules and estimate the selfdiffusion coefficients of water in the Nafion 117. Greek Symbol

High-intensity Focused Ultrasound Ablation of Soft-tissue Tumors and Assessment of Treatment Response with Multiparametric Magnetic Resonance Imaging: Preliminary Study Using Rabbit VX2 Tumor Model

BackgroundHigh-intensity focused ultrasound (HIFU) is an emerging technique for noninvasive ablative treatment. However, HIFU has rarely been performed for the treatment of soft-tissue tumors. Thus, we aimed to assess the feasibility and safety of performing extracorporeal HIFU for the treatment of soft-tissue tumor. The treatment response was assessed using functional magnetic resonance imaging (MRI) techniques.Materials and methodsIn the rabbit VX2 intramuscular tumor model, HIFU was performed using an extracorporeal HIFU device (YDME FEP-BY02) by varying the electric power from 50 to 400 W, with the other parameters being fixed. The HIFU beam was insonated to one layer of focal spots having a depth of 8 mm. The degree of ablation was evaluated by histological examination and functional MRI techniques including dynamic contrast-enhanced MRI (DCE-MRI) and apparent diffusion coefficient (ADC) map. The presence of skin burn was also evaluated.ResultsApplying HIFU with an electric power of 200 W discretely produced the ablation zone without skin burn as planned before treatment (maximal depth: 8–9 mm), which shows the suitability of using HIFU (with 200 W electric power) for the treatment of soft-tissue tumors. By contrast, HIFU with an electric power of 100 W produced an ill-marginated ablation zone with internal residual tumor foci, and HIFU with 300–400 W produced ablation zones with a maximum depth of 13–24 mm, which far exceeded the planned depth and caused skin burn. Perfusion maps of DCE-MRI demonstrated the devascularized ablation zone more conspicuously than conventional contrast-enhanced T1-weighted images, and ADC map demonstrated the surrounding edema or granulation tissue better than conventional T2-weighted images.ConclusionExtracorporeal HIFU treatment for soft-tissue tumor may be a feasible approach with adjustment of input energy level. For post-treatment assessment, functional MRI techniques including DCE-MRI and ADC map may be useful and complementary to conventional MRI

Chiral orbital-angular-momentum in the surface states of Bi2Se3

Locking of the spin of a quasi-particle to its momentum in split bands of on the surfaces of metals and topological insulators (TIs) is understood in terms of Rashba effect where a free electron in the surface states feels an effective magnetic field. On the other hand, the orbital part of the angular momentum (OAM) is usually neglected. We performed angle resolved photoemission experiments with circularly polarized lights and first principles density functional calculation with spin-orbit coupling on a TI, Bi2Se3, to study the local OAM of the surface states. We show from the results that OAM in the surface states of Bi2Se3 is significant and locked to the electron momentum in opposite direction to the spin, forming chiral OAM states. Our finding opens a new possibility to have strong light-induced spin-polarized current in the surface states.Comment: 5 pages, 4 figures, 1 tabl

Plexiform Angiomyxoid Myofibroblastic Tumor of the Stomach: A Case Report

Plexiform angiomyxoid myofibroblastic tumor (PAMT) is a recently described mesenchymal tumor of the stomach. We report the first case of PAMT in Korea. A 52-yr-old man underwent esophagogastroduodenoscopy due to dyspepsia for 2 yr. There was a submucosal mass with small mucosal ulceration in the gastric antrum. The tumor measured 3.5 × 2.3 cm in size and showed multinodular plexiform growth pattern of bland-looking spindle cells separated by an abundant myxoid or fibromyxoid matrix rich in small thin-walled blood vessels. The tumor cells were negative for CD117 (c-KIT), CD34 and S-100 protein, but diffusely positive for smooth muscle actin consistent with predominant myofibroblastic differentiation. The patient is doing well without recurrence or metastasis for 5 months after surgery. Although there have been limited follow-up data, PAMT is regarded as a benign gastric neoplasm with histological and immunohistochemical charateristics distinguished from gastrointestinal stromal tumor and other mesenchymal tumors of the stomach

Flash Pulmonary Edema in a Patient With Unilateral Renal Artery Stenosis and Bilateral Functioning Kidneys

Flash pulmonary edema typically exhibits sudden onset and resolves rapidly. It generally is associated with bilateral renal artery stenosis or unilateral stenosis in conjunction with a single functional kidney. We describe a patient who presented with flash pulmonary edema treated by percutaneous therapy with stent implantation. Our case is unique in that the flash pulmonary edema occurred in the setting of unilateral renal artery stenosis with bilateral functioning kidneys