Korea University

About: Korea University is a education organization based out in Seoul, South Korea. It is known for research contribution in the topics: Population & Thin film. The organization has 39756 authors who have published 82424 publications receiving 1860927 citations. The organization is also known as: Bosung College & Bosung Professional College.

α-Synuclein Activates Microglia by Inducing the Expressions of Matrix Metalloproteinases and the Subsequent Activation of Protease-Activated Receptor-1

Abstract: The mutation or overexpression of alpha-synuclein protein plays a pivotal role in the pathogenesis of Parkinson's disease. In our preliminary experiments, we found that alpha-synuclein induced the expression of matrix metalloproteinases (MMPs) (MMP-1, -3, -8, and -9) in rat primary cultured microglia. Thus, the current study was undertaken to determine the roles of MMPs in alpha-synuclein-induced microglial activation. The inhibition of MMP-3, -8, or -9 significantly reduced NO and reactive oxygen species levels and suppressed the expression of TNF-alpha and IL-1beta. Notably, MMP-8 inhibitor suppressed TNF-alpha production more efficaciously than MMP-3 or MMP-9 inhibitors. Inhibition of MMP-3 or -9 also suppressed the activities of MAPK, NF-kappaB, and AP-1. Previously, protease-activated receptor-1 (PAR-1) has been associated with the actions of MMPs, and thus, we further investigated the role of PAR-1 in alpha-synuclein-induced inflammatory reactions. A PAR-1-specific inhibitor and a PAR-1 antagonist significantly suppressed cytokine levels, and NO and reactive oxygen species production in alpha-synuclein-treated microglia. Subsequent PAR-1 cleavage assay revealed that MMP-3, -8, and -9, but not alpha-synuclein, cleaved the synthetic peptide containing conventional PAR-1 cleavage sites. These results suggest that MMPs secreted by alpha-synuclein-stimulated microglia activate PAR-1 and amplify microglial inflammatory signals in an autocrine or paracrine manner. Furthermore, our findings suggest that modulation of the activities of MMPs and/or PAR-1 may provide a new therapeutic strategy for Parkinson's disease.

Nitric oxide negatively regulates c-Jun N-terminal kinase/stress-activated protein kinase by means of S-nitrosylation

Abstract: NO, produced from l-arginine in a reaction catalyzed by NO synthase, is an endogenous free radical with multiple functions in mammalian cells. Here, we demonstrate that endogenously produced NO can suppress c-Jun N-terminal kinase (JNK) activation in intact cells. Treatment of BV-2 murine microglial cells with IFN-gamma induced endogenous NO production, concomitantly suppressing JNK1 activation. Similarly, IFN-gamma induced suppression of JNK1 activation in RAW264.7 murine macrophage cells and rat alveolar macrophages. The IFN-gamma-induced suppression of JNK1 activation in BV-2, RAW264.7, or rat alveolar macrophage cells was completely prevented by N(G)-nitro-l-arginine, a NO synthase inhibitor. Interestingly, the IFN-gamma-induced suppression of JNK1 activation was not affected by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of guanylyl cyclase. 8-Bromo-cGMP, a membrane-permeant analogue of cGMP, did not change JNK1 activation in intact cells either. In contrast, S-nitro-N-acetyl-dl-penicillamine (SNAP), a NO donor, inhibited JNK1 activity in vitro. Furthermore, a thiol reducing agent, DTT, reversed not only the in vitro inhibition of JNK1 activity by SNAP but also the in vivo suppression of JNK1 activity by IFN-gamma. Substitution of serine for cysteine-116 in JNK1 abolished the inhibitory effect of IFN-gamma or SNAP on JNK1 activity in vivo or in vitro, respectively. Moreover, IFN-gamma enhanced endogenous S-nitrosylation of JNK1 in RAW264.7 cells. Collectively, our data suggest that endogenous NO mediates the IFN-gamma-induced suppression of JNK1 activation in macrophage cells by means of a thiol-redox mechanism.

Overcoming the Limits of Hypoxia in Photodynamic Therapy: A Carbonic Anhydrase IX-Targeted Approach.

Abstract: A major challenge in photodynamic cancer therapy (PDT) is avoiding PDT-induced hypoxia, which can lead to cancer recurrence and progression through activation of various angiogenic factors and significantly reduce treatment outcomes. Reported here is an acetazolamide (AZ)-conjugated BODIPY photosensitizer (AZ-BPS) designed to mitigate the effects of PDT-based hypoxia by combining the benefits of anti-angiogenesis therapy with PDT. AZ-BPS showed specific affinity to aggressive cancer cells (MDA-MB-231 cells) that overexpress carbonic anhydrase IX (CAIX). It displayed enhanced photocytotoxicity compared to a reference compound, BPS, which is an analogous PDT agent that lacks an acetazolamide unit. AZ-BPS also displayed an enhanced in vivo efficacy in a xenograft mouse tumor regrowth model relative to BPS, an effect attributed to inhibition of tumor angiogenesis by both PDT-induced ROS generation and CAIX knockdown. AZ-BPS was evaluated successfully in clinical samples collected from breast cancer patients. ...

Biochar Aging: Mechanisms, Physicochemical Changes, Assessment, And Implications for Field Applications.

Abstract: Biochar has triggered a black gold rush in environmental studies as a carbon-rich material with well-developed porous structure and tunable functionality. While much attention has been placed on its apparent ability to store carbon in the ground, immobilize soil pollutants, and improve soil fertility, its temporally evolving in situ performance in these roles must not be overlooked. After field application, various environmental factors, such as temperature variations, precipitation events and microbial activities, can lead to its fragmentation, dissolution, and oxidation, thus causing drastic changes to the physicochemical properties. Direct monitoring of biochar-amended soils can provide good evidence of its temporal evolution, but this requires long-term field trials. Various artificial aging methods, such as chemical oxidation, wet-dry cycling and mineral modification, have therefore been designed to mimic natural aging mechanisms. Here we evaluate the science of biochar aging, critically summarize aging-induced changes to biochar properties, and offer a state-of-the-art for artificial aging simulation approaches. In addition, the implications of biochar aging are also considered regarding its potential development and deployment as a soil amendment. We suggest that for improved simulation and prediction, artificial aging methods must shift from qualitative to quantitative approaches. Furthermore, artificial preaging may serve to synthesize engineered biochars for green and sustainable environmental applications.

The selective detection of C2H5OH using SnO2–ZnO thin film gas sensors prepared by combinatorial solution deposition

Abstract: Sensing materials for selective detection of C2H5OH were designed using combinatorial solution deposition of SnO2–ZnO thin films. The SnO2–ZnO composite sensor prepared by alternate deposition of 10 droplets of SnO2 and ZnO sols (S50Z50 sensor) showed a high response to 200 ppm C2H5OH (S(ethanol) = Ra/Rg = 4.69, Ra: resistance in air, Rg: resistance in gas) at 300 °C, while the gas responses to 100 ppm C3H8, 100 ppm CO, 200 ppm H2, and 5 ppm NO2 ranged from 1.11 to 1.19. The S(ethanol) value of the S50Z50 sensor was twice that to 200 ppm CH3COCH3 (S(acetone)). In contrast, the S(ethanol) and S(acetone) of pure SnO2 and ZnO thin films were similar to each other. The heterostructure between SnO2 and ZnO was suggested as one of the probable reasons for the successful discrimination between C2H5OH and CH3COCH3.