Bardoxolone treatment alleviates lipopolysaccharide (LPS)-induced acute lung injury through suppressing inflammation and oxidative stress regulated by Nrf2 signaling.

Nuclear factor-erythroid 2 related factor 2 (Nrf2) plays critical roles in attenuating various inflammation- and oxidative stress-induced diseases, including acute lung injury (ALI). Bardoxolone (Bard), a synthetic triterpenoid based on natural product oleanolic acid, is one of the most potent Nrf2 activator. However, if Bard could prevent lipopolysaccharide (LPS)-induced ALI by inducing Nrf2 activation and its down-streaming signals, is still poorly understood. In this study, we attempted to explore the protective effect of Bard on ALI and the underlying molecular mechanisms. The results indicated that Bard significantly attenuated ALI through reducing the lung wet/dry weight ratio and protein concentration, neutrophil infiltration, malondialdehyde (MDA) and myeloperoxidase (MPO) levels, and improving superoxide dismutase (SOD) and glutathione (GSH) activities. In addition, Bard effectively ameliorated histopathological alterations, reactive oxygen species (ROS) production, pro-inflammatory cytokines release, and the expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX2) and high mobility group box 1 (HMGB1). Moreover, the inhibitory role of Bard in inflammation was also attributed to its suppression of nuclear factor-κB (NF-κB) signaling. Furthermore, the activation of mitogen-activated protein kinases (MAPKs) signaling, including p38, extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK), induced by LPS was substantially ameliorated by Bard. The beneficial effects of Bard on ALI were confirmed in LPS-incubated cells in vitro. Meanwhile, the in vitro studies also demonstrated that Bard-improved ALI was largely due to its role in inducing Nrf2 signaling through a dose-dependent manner. Importantly, we found that Bard-attenuated histological changes, inflammation, ROS production, NF-κB and MAPKs signaling in Nrf2+/+ mice were significantly abolished in mice with Nrf2 knockout. Therefore, our study for the first time provided evidence that Bard could effectively ameliorate LPS-induced ALI by reducing oxidative stress and inflammation mainly through the activation of Nrf2 signaling.

Multi/demulti-plexer based on transverse mode conversion in photonic crystal waveguides.

A novel mode multiplexer and demultiplexer (MMUX/DEMMUX) based on 2-D photonic crystal (PC) at 1550 nm is proposed. The PC-based mode MMUX/DEMMUX including mode conversion function with a single-mode and multi-mode waveguides can be realized by quasi phase-matching TE(0) & TE(1) modes of two waveguides. 2DFinite-Difference-Time-Domain and beam propagation methods are used for simulation. The results show that PC-based mode MMUX/DEMMUX has the potential for high-capacity MDM optical communication systems with a low insertion loss (<0.36dB), low mode crosstalk (< -20.9 dB) and wide bandwidth (~100 nm).

Apelin attenuates the osteoblastic differentiation of aortic valve interstitial cells via the ERK and PI3-K/Akt pathways.

Aortic valve calcification (AVC), which used to be recognized as a passive and irreversible process, is now widely accepted as an active and regulated process characterized by osteoblastic differentiation of aortic valve interstitial cells (AVICs). Apelin, the endogenous ligand for G-protein-coupled receptor APJ, was found to have protective cardiovascular effects in several studies. However, the effects and mechanisms of apelin on osteoblastic differentiation of AVICs have not been elucidated. Using a pro-calcific medium, we devised a method to produce calcific human AVICs. These cells were used to study the relationship between apelin and the osteoblastic calcification of AVICs and the involved signaling pathways. Alkaline phosphatase (ALP) activity/expression and runt-related transcription factor 2 (Runx2) expression were examined as hallmark proteins in this research. The involved signaling pathways were studied using the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, and the phosphatidylinositol 3-kinase (PI3-K) inhibitor, LY294002. The results indicate that apelin attenuates the expression and activity of ALP, the expression of Runx2, and the formation of mineralized nodules. This protective effect was dependent on the dose of apelin, reaching the maximum at 100 pM, and was connected to activity of ERK and Akt (a downstream effector of PI3-K). The activation of ERK and PI3-K initiated the effects of apelin on ALP activity/expression and Runx2, but PD98059 and LY294002 abolished the effect. These results demonstrate that apelin attenuates the osteoblastic differentiation of AVICs via the ERK and PI3-K/Akt pathway.

Effectiveness of YouTube as a Source of Medical Information on Heart Transplantation.

BACKGROUND: In this digital era, there is a growing tendency to use the popular Internet site YouTube as a new electronic-learning (e-learning) means for continuing medical education. Heart transplantation (HTx) remains the most viable option for patients with end-stage heart failure or severe coronary artery disease. There are plenty of freely accessible YouTube videos providing medical information about HTx. OBJECTIVE: The aim of the present study is to determine the effectiveness of YouTube as an e-learning source on HTx. METHODS: In order to carry out this study, YouTube was searched for videos uploaded containing surgical-related information using the four keywords: (1) "heart transplantation", (2) "cardiac transplantation", (3) "heart transplantation operation", and (4) "cardiac transplantation operation". Only videos in English (with comments or subtitles in English language) were included. Two experienced cardiac surgeons watched each video (N=1800) and classified them as useful, misleading, or recipients videos based on the HTx-relevant information. The kappa statistic was used to measure interobserver variability. Data was analyzed according to six types of YouTube characteristics including "total viewership", "duration", "source", "days since upload", "scores" given by the viewers, and specialized information contents of the videos. RESULTS: A total of 342/1800 (19.00%) videos had relevant information about HTx. Of these 342 videos, 215 (62.8%) videos had useful information about specialized knowledge, 7/342 (2.0%) were found to be misleading, and 120/342 (35.1%) only concerned recipients' individual issues. Useful videos had 56.09% of total viewership share (2,175,845/3,878,890), whereas misleading had 35.47% (1,375,673/3,878,890). Independent user channel videos accounted for a smaller proportion (19% in total numbers) but might have a wider impact on Web viewers, with the highest mean views/day (mean 39, SD 107) among four kinds of channels to distribute HTx-related information. CONCLUSIONS: YouTube videos on HTx benefit medical professionals by providing a substantial amount of information. However, it is a time-consuming course to find high-quality videos. More authoritative videos by trusted sources should be posted for dissemination of reliable information. With an improvement of ranking system and content providers in future, YouTube, as a freely accessible outlet, will help to meet the huge informational needs of medical staffs and promote medical education on HTx.

Optically-controlled high-speed terahertz wave modulator based on nonlinear photonic crystals.

An optically-controlled terahertz (THz) modulator based on nonlinear photonic crystals (PCs) is proposed, which has the merits of high speed, compactness and easy integration. The PC structure consists of point and line defects. High speed modulation of THz wave can be realized by filling one of the point defects with organic polymer polyaniline which has rapid nonlinear response time. Simulation results show that the modulation rate, modulation depth and insertion loss of the modulator achieve 2.5 GHz, 20.3 dB and 1.02 dB, respectively.

[Quantitation of telomerase activity using the polymerase chain reaction-based enzyme immunoassay and its clinical application].

OBJECTIVE: To investigate detective methodology of telomerase activity and its clinical application. METHODS: The telomerase activity was quantitated by polymerase chain reaction-base enzyme immunoassay (PCR-EIA). The TS primer was biotinylated (TS-B), and CX primer was digoxigeninated (CX-D). The amplicons containing TS-B were combined with microtiter plate coated streptavidin, then combined with anti-digoxigenin antibody labeled with POD and finally reacted to tetramethylbenzidine substrate solution. RESULTS: Telomerase activity measured by the PCR-EIA method was comparable to that obtained from TRAP-silver stain protocol. The CV of the PCR-EIA method was 4.138%. Telomerase activity was detected in 90% of various tumer tissues. In control tissues, telomerase activity was detected only in 7.1%. CONCLUSION: The PCR-EIA method offers a rapid, quantitative, and nonisotopic assay for the determination of telomerase activity. It is simpler than silver stain protocol. The detection of telomerase activity may play a significant role in the diagnosis of clinical tumors.