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

Influence of Socioeconomic Factors, Gender and Indigenous Status on Smoking in Taiwan.

The indigenous Austronesian minority of Taiwan is heavily affected by health disparities which may include suffering from a greater burden of the tobacco epidemic. While a lack of representative data has historically precluded an investigation of the differences in smoking between Taiwanese ethnicities, these data have recently become available through an annual population-based telephone survey conducted by the Health Promotion Administration, Ministry of Health and Welfare (previously known as the Bureau of Health Promotion (BHP), Department of Health). We used the BHP monitoring data to observe the prevalence of smoking and environmental tobacco smoke exposure among indigenous and non-indigenous Taiwanese surrounding a tobacco welfare tax increase in 2006, investigate ethnic differences in smoking prevalence and environmental tobacco smoke exposure each year between 2005 and 2008, and perform multiple logistic regression to estimate measures of association between potential risk factors and smoking status. Despite significant ethnic and gender differences in smoking prevalence, smoking status was not found to be significantly associated with ethnicity after controlling for socioeconomic and demographic factors

Community-acquired Methicillin-resistant Staphylococcus aureus in Children, Taiwan

Highly virulent community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) with Panton-Valentine leukocidin (PVL) is common worldwide. Using antimicrobial drug susceptibility testing, staphylococcal cassette chromosome mec typing, exotoxin profiling, and pulsed-field gel electrophoresis typing, we provide evidence that supports the relationship between nasal strains of PVL-positive MRSA and community-acquired disease

Changing trends in antimicrobial resistance of major bacterial pathogens, 1985–2005: A study from a medical center in northern Taiwan

BackgroundAntimicrobial resistance is a major health problem worldwide. We evaluated the antimicrobial resistance trends of 16 major bacterial pathogens at a tertiary medical center in northern Taiwan.MethodsWe conducted a retrospective review of annual summary documents for antimicrobial susceptibility of clinically isolated gram-positive and gram-negative bacteria from 1985 to 2005. The numbers of isolates and susceptibilities were calculated for three 7-year periods: first period, 1985–1991; second period, 1992–1998; and the third period, 1999–2005.ResultsDuring the 21-year period, 219,715 bacterial pathogens were identified. A significant increase in incidence over time was found for methicillin-resistant Staphylococcus aureus, methicillin-resistant S epidermidis, penicillin-nonsusceptible Streptococcus pneumoniae, erythromycin-resistant S pneumoniae, vancomycin-resistant enterococci, cefotaxime/ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae, and imipenem-resistant Acinetobacter baumannii. Additionally, a significant increase in ciprofloxacin resistance rates over time from 1996 to 2005 was noted for E coli, Enterobacter cloacae, and A baumannii (through 1997 to 2005). However, a significant decrease in erythromycin resistance rate with time from 1999 to 2005 was found for Groups A and B streptococci, non-A, B, D streptococci, and S pneumoniae.ConclusionResistance to antimicrobial agents increased rapidly in the past two decades in Taiwan and has become very common in major bacterial pathogens. Continuous enforcement of policies to limit use of antimicrobial agents and active surveillance of antimicrobial resistance through a nationwide system are both warranted

Study of sponge gourd ascorbate peroxidase and winter squash superoxide dismutase under respective flooding and chilling stresses

AbstractThe objectives of this work were to study the responses of ascorbate peroxidase (APX), catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), and physiological parameters of bitter melon (BM), sponge gourd (SG), and winter squash (WS) under waterlogged and low temperature conditions. The BM and SG plants were subjected to 0–72h flooding treatments. Moreover, BM and WS plants were exposed to chilling at 12/7°C (day/night) for 0–72h. The results show that different genotypes responded differently to environmental stress according to their various antioxidant enzymes and physiological parameters. The activity of APX in roots and leaves of SG plants significantly higher than that of BM plants during continuous flooding. Significant increases in SOD activity in leaves of WS plants were also observed throughout the entire chilling duration compared to BM plants. On the basis of our observations, we conclude that increased APX and SOD activities provide SG and WS plants with increased waterlogging and chilling stress tolerance, respectively. Both APX and SOD activities can be used for selecting BM lines with the best tolerances to water logging and chilling stresses

Current Status of the Immunomodulation and Immunomediated Therapeutic Strategies for Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, and CD4+ T cells form the core immunopathogenic cascade leading to chronic inflammation. Traditionally, Th1 cells (interferon-γ-producing CD4+ T cells) driven by interleukin 12 (IL12) were considered to be the encephalitogenic T cells in MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Currently, Th17 cells (Il17-producing CD4+ T cells) are considered to play a fundamental role in the immunopathogenesis of EAE. This paper highlights the growing evidence that Th17 cells play the core role in the complex adaptive immunity of EAE/MS and discusses the roles of the associated immune cells and cytokines. These constitute the modern immunological basis for the development of novel clinical and preclinical immunomodulatory therapies for MS discussed in this paper

Microyielding of Core-Shell Crystal Dendrites in a Bulk-metallic-glass Matrix Composite

In-situ synchrotron x-ray experiments have been used to follow the evolution of the diffraction peaks for crystalline dendrites embedded in a bulk metallic glass matrix subjected to a compressive loading-unloading cycle. We observe irreversible diffraction-peak splitting even though the load does not go beyond half of the bulk yield strength. The chemical analysis coupled with the transmission electron microscopy mapping suggests that the observed peak splitting originates from the chemical heterogeneity between the core (major peak) and the stiffer shell (minor peak) of the dendrites. A molecular dynamics model has been developed to compare the hkl-dependent microyielding of the bulk metallic-glass matrix composite. The complementary diffraction measurements and the simulation results suggest that the interface, as Maxwell damper, between the amorphous matrix and the (211) crystalline planes relax under prolonged load that causes a delay in the reload curve which ultimately catches up with the original path

TNF-α Mediates Eosinophil Cationic Protein-induced Apoptosis in BEAS-2B Cells

<p>Abstract</p> <p>Background</p> <p>Eosinophilic granulocytes are important for the human immune system. Many cationic proteins with cytotoxic activities, such as eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN), are released from activated eosinophils. ECP, with low RNase activity, is widely used as a biomarker for asthma. ECP inhibits cell viability and induces apoptosis to cells. However, the specific pathway underlying the mechanisms of ECP-induced cytotoxicity remains unclear. This study investigated ECP-induced apoptosis in bronchial epithelial BEAS-2B cells and elucidated the specific pathway during apoptosis.</p> <p>Results</p> <p>To address the mechanisms involved in ECP-induced apoptosis in human BEAS-2B cells, investigation was carried out using chromatin condensation, cleavage of poly (ADP-ribose) polymerase (PARP), sub-G1 distribution in cell cycle, annexin V labeling, and general or specific caspase inhibitors. Caspase-8-dependent apoptosis was demonstrated by cleavage of caspase-8 after recombinant ECP treatment, accompanied with elevated level of tumor necrosis factor alpha (TNF-α). Moreover, ECP-induced apoptosis was effectively inhibited in the presence of neutralizing anti-TNF-α antibody.</p> <p>Conclusion</p> <p>In conclusion, our results have demonstrated that ECP increased TNF-α production in BEAS-2B cells and triggered apoptosis by caspase-8 activation through mitochondria-independent pathway.</p

Changes in the Nasal Colonization with Methicillin-Resistant Staphylococcus aureus in Children: 2004-2009

BACKGROUND: Staphylococcus aureus is an important cause of infection, particularly in persons colonized with this organism. This study compared the annual prevalence and microbiological characteristics of methicillin-resistant S. aureus (MRSA) nasal colonization in Taiwanese children from 2004 through 2009. Risk factors for MRSA were determined for the overall study period. METHODS: Children from birth to ≤14 years of age presenting for health maintenance visits or attending 1 of 57 kindergartens were recruited. Nasal swabs were obtained, and a questionnaire was administered. The prevalence and microbiological characteristics of MRSA colonization were also calculated for two 3-year periods: 2004-2006 and 2007-2009. RESULTS: Cultures of the anterior nares were positive for S. aureus in 824 (25.8%) of the 3,200 children, and MRSA colonization was found in 371 (11.6%) children. The prevalence of S. aureus colonization decreased from 28.1% in 2004-2006 to 23.3% in 2007-2009 (p<0.01), whereas the prevalence of MRSA colonization increased from 8.1% to 15.1% during this period (p<0.0001). Multivariate analysis revealed that the independent risk factors for MRSA carriage were different for male and female children, and also among age groups. Most MRSA isolates belonged to sequence type 59 (ST59) (86.3%); however, a multiresistant MRSA clone with ST338 background emerged in 2007-2009. Ten (62.5%) of the 16 MRSA isolates expressed the genotypic profile ST338/staphylococcal cassette chromosome mec V(T)/Panton-Valentine leukocidin-positive/staphylococcal enterotoxin B-positive, and differed only in their antimicrobial susceptibility patterns. CONCLUSION: The prevalence of nasal colonization by MRSA increased among healthy Taiwanese children from 2004-2006 to 2007-2009, despite an overall decrease in the prevalence of nasal colonization by S. aureus. A multiresistant MRSA clone characterized as ST338 was identified from these children

Quantitative pinch stimulator for exploring evoked nociceptive responses: A pilot study

<p>Abstract</p> <p>Background</p> <p>A mechanical noxious stimulator is useful for studies of pain, both for clinic and basic research. We propose to use a pinch stimulator that can not only generate a quantitative, reproducible noxious pinch but also simultaneously provide a synchronous external trigger signal, which is essential for acquisition of evoked potentials.</p> <p>Methods</p> <p>For ethical considerations, audible and visual aids were incorporated so that pinch force could be regulated within a predetermined level. Reproducibility of the nociceptive responses evoked by this device was validated. The device was constructed with a simple circuit, and the element build-in was delicately selected for the minimum required to produce evoked potentials.</p> <p>Results</p> <p>The magnitude of the force output is linearly proportional to the volts produced by the device (i.e., during the pinch). Increases in force correspond to increases in the number of action potentials induced.</p> <p>Conclusions</p> <p>This device may be useful for studying the mechanisms of nociceptive signal processing in the brain through application of reproducible, noxious pinch stimuli.</p