A naturally occurring carotenoid, lutein, reduces PDGF and H2O2 signaling and compromised migration in cultured vascular smooth muscle cells

<p>Abstract</p> <p>Background</p> <p>Platelet-derived growth factor (PDGF) is a potent stimulator of growth and motility of vascular smooth muscle cells (VSMCs). Abnormalities of PDGF/PDGF receptor (PDGFR) are thought to contribute to vascular diseases and malignancy. We previously showed that a carotenoid, lycopene, can directly bind to PDGF and affect its related functions in VSMCs. In this study we examined the effect of the other naturally occurring carotenoid, lutein, on PDGF signaling and migration in VSMCs.</p> <p>Methods</p> <p>Western blotting was performed to examine PDGF and H₂O₂signaling. Flowcytometry was used to determine PDGF binding to VSMCs. Fluorescence microscopy was performed to examine intracellular ROS production. Modified Boyden chamber system (Transwell apparatus) was used for migration assay.</p> <p>Results</p> <p>Lutein reduced PDGF signaling, including phosphorylation of PDGFR-β and its downstream protein kinases/enzymes such as phospholipase C-γ, Akt, and mitogen-activated protein kinases (MAPKs). Although lutein possesses a similar structure to lycopene, it was striking that lutein inhibited PDGF signaling through a different way from lycopene in VSMCs. Unlike lycopene, lutein not only interacted with (bound to) PDGF but also interfered with cellular components. This was evidenced that preincubation of PDGF with lutein and treatment of VSMCs with lutein followed by removing of lutein compromised PDGF-induced signaling. Lutein reduced PDGF-induced intracellular reactive oxygen species (ROS) production and attenuated ROS- (H₂O₂-) induced ERK1/2 and p38 MAPK activation. A further analysis indicated lutein could inhibit a higher concentration of H₂O₂-induced PDGFR signaling, which is known to act through an oxidative inhibition of protein tyrosine phosphatase. Finally, we showed that lutein functionally inhibited PDGF-induced VSMC migration, whereas its stereo-isomer zeaxanthin did not, revealing a special action of lutein on VSMCs.</p> <p>Conclusions</p> <p>Our study reveals a differential action mechanism of lutein from other reported caroteinoids and suggests a possible beneficial effect of lutein but not zeaxanthin on prevention of vascular diseases.</p

Effects of computer-based cognitive training combined with physical training for older adults with cognitive impairment: A four-arm randomized controlled trial

OBJECTIVE: Combined physical (PHY) and cognitive (COG) training in sequential (SEQ) and simultaneous (SIMUL) sessions may delay the progression of cognitive impairment. To date, no study has directly compared in older adults with cognitive impairment the effects of COG training, PHY training, SEQ motor-cognitive training and SIMUL motor-cognitve training on specific indices of cognitive performance and activities of daily living (ADL). The purpose of this study was to determine whether SEQ and SIMUL motor-cognitive training can improve treatment outcomes compared with PHY or COG training alone. We also aimed to compare the effects of SEQ versus SIMUL motor-cognitive training on cognitive functions and instrumental ADL (IADL) in older adults with cognitive impairment. METHODS: A cluster randomized controlled trial was conducted. Eighty older adults with cognitive impairment were randomly assigned to COG, PHY, SEQ or SIMUL training groups. The intervention consisted of 90-min training sessions, totaling 36 sessions. Outcome measures were the Montreal Cognitive Assessment, three subtests of the Wechsler Memory Scale (WMS) and the Lawton IADL scale. RESULTS: Significant interaction effects between group and time were found in WMS-spatial span ( CONCLUSIONS: Our study showed SEQ and SIMUL motor-cognitive training led to more pronounced improvements in visuospatial working memory or verbal memory compared with isolated COG or PHY training for community-based older adults with cognitive impairment. For enhancing effects on IADL, we suggest the use of sensitive measurement tools and context-enriched cognitive training involving real-life task demands

Early Warning System (EWS) of Currency Crises: An Empirical Study of Some SEACEN Countries

This paper investigates the macroeconomic factors in predicting the currency crises in a sample of 7 SEACEN countries using the logit econometric models. The empirical results indicate that the variables that may help predict the timing of the currency crises include real US interest rate, ratio of import to foreign reserves, real effective exchange rate, or money multiplier. In particular, the model that includes real US interest rate and ratio of import to foreign reserves can forecast better than other models for most of the 7 sample countries.

Low Cost Seismic Network Practical Applications for Producing Quick Shaking Maps in Taiwan

Two major earthquakes of ML greater than 6.0 occurred in Taiwan in the first half of 2013. The vibrant shaking brought landslides, falling rocks and casualties. This paper presents a seismic network developed by National Taiwan University (NTU) with 401 Micro-Electro Mechanical System (MEMS) accelerators. The network recorded high quality strong motion signals from the two events and produced delicate shaking maps within one minute after the earthquake occurrence. The high shaking regions of the intensity map produced by the NTU system suggest damage and casualty locations. Equipped with a dense array of MEMS accelerometers, the NTU system is able to accommodate 10% signals loss from part of the seismic stations and maintain its normal functions for producing shaking maps. The system also has the potential to identify the rupture direction which is one of the key indices used to estimate possible damage. The low cost MEMS accelerator array shows its potential in real-time earthquake shaking map generation and damage avoidance

Finding a Fair Land Dispute Settlement Mechanism Between Adat Law Community Vs. Investor

Land utilization for investment in local areas raises various land related problems that ends with conflicts within the community. A conflict that occurs, usually begins with the management of communal land “tanah ulayat” within the adat law community environment, and in this case, land utilization that is managed by the third party (investors). The basic problem is the difference of perception and expectations toward the company that exists in the land which is claimed by the community. Both parties have their own claim on the land based on each legal systems, in this situation adat law or local law faced with state law which is used by investors. So far, the Indonesian government has yet to have legal grounds in giving a directions for land dispute/conflict settlement mechanism. This paper attempts to give an input regarding a land dispute settlement mechanism that can be accepted for all disputing parties. The paper features critical analysis using legal pluralism approach towards related government policies and technical regulations in the ministerial level. These regulations, among others are, Minister of Agrarian Regulation No. 5 of 1999 on the Guidance for Dispute Settlement of Communal Land Rights, and Ministry of Agrarian and Spatial Affairs Regulation No. 9 of 2015 on Procedures of Appointment of Communal Land Rights for Adat Law Community and Communities Located in certain regions, also the draft of Law regarding Recognition and Protection of Adat Law Community

Extracorporeal membrane oxygenation for neonatal congenital diaphragmatic hernia: The initial single-center experience in Taiwan

Background/Purpose Extracorporeal membrane oxygenation (ECMO) is a treatment option for stabilizing neonates with congenital diaphragmatic hernia (CDH) in a critical condition when standard therapy fails. However, the use of this approach in Taiwan has not been previously reported. Methods The charts of all neonates with CDH treated in our institute during the period 2007–2014 were reviewed. After 2010, patients who could not be stabilized with conventional treatment were candidates for ECMO. We compared the demographic data of patients with and without ECMO support. The clinical course and complications of ECMO were also reviewed. Results We identified 39 neonates with CDH with a median birth weight of 2696 g (range, 1526–3280 g). Seven (18%) of these patients required ECMO support. The APGAR score at 5 minutes differed significantly between the ECMO and non-ECMO groups. The survival rate was 84.6% (33/39) for all CDH patients and 57.1% (4/7) for the ECMO group. The total ECMO bypass times in the survivors was in the range of 5–36 days, whereas all nonsurvivors received ECMO for at least 36 days (mean duration, 68 days). Surgical bleeding occurred in four of seven patients in the ECMO group. Conclusion The introduction of ECMO rescued some CDH patients who could not have survived by conventional management. Prolonged (i.e., > 36 days) ECMO support had no benefit for survival

Methyl 1-benzyl-1H-1,2,3-triazole-4-carboxyl­ate

In the title compound, C11H11N3O2, prepared by the [3+2] cycloaddition reaction of benzyl azide with methyl propiolate, the dihedral angle between the ring planes is 67.87 (11)°