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

Plasma levels in sepsis patients of annexin A1, lipoxin A4, macrophage inflammatory protein-3a, and neutrophil gelatinase-associated lipocalin

AbstractBackgroundThe relationship between the various cytokine responses that occur during sepsis remains controversial. Emerging evidence indicates that the proinflammatory and anti-inflammatory responses are regulated simultaneously from the beginning of sepsis. However, the roles of the novel anti-inflammatory mediators annexin (Anx)A1 and lipoxin (LX)A4 and the proinflammatory cytokines neutrophil gelatinase-associated lipocalin (NGAL) and macrophage inflammatory protein (MIP)-3a have been studied.MethodsIn this study, the plasma levels of AnxA1, LXA4, NGAL, MIP-3a, interleukin (IL)-8 and IL-6 in patients with sepsis were determined on admission to the intensive care unit. The patients were classified into survivors and non-survivors based on their outcome on day 28.ResultsAnxA1 and LXA4 levels were decreased in sepsis patients compared with control patients, whereas the levels of the proinflammatory cytokines MIP-3a, NGAL, IL-8, and IL-6 were elevated. Furthermore, a significantly higher level of MIP-3a was detected in nonsurviving patients compared with surviving patients (p < 0.05), whereas there were no significant differences between these two groups for the levels of the other mediators. Correlation analysis demonstrated that only NGAL level was closely correlated with the level of IL-6. Univariate analysis indicated that the levels of MIP-3a and IL-8 were independent factors associated with patient survival, but this was not confirmed by the multivariate analysis.ConclusionAnxA1 and LXA4 plasma levels were found to be decreased in sepsis patients, whereas the levels of MIP-3a and NGAL were found to be elevated. This warrants further study in order to determine the clinical implications of these changes

Differentiation of Foot-and-Mouth Disease-Infected pigs from Vaccinated Pigs Using Antibody-Detecting Sandwich ELISA

The presence of serum antibodies for nonstructural proteins of the foot-and-mouth disease virus (FMDV) can differentiate FMDV-infected animals from vaccinated animals. In this study, a sandwich ELISA was developed for rapid detection of the foot-and-mouth disease (FMD) antibodies; it was based on an Escherichia coli-expressed, highly conserved region of the 3ABC nonstructural protein of the FMDV O/TW/99 strain and a monoclonal antibody derived from the expressed protein. The diagnostic sensitivity of the assay was 98.4%, and the diagnostic specificity was 100% for naïve and vaccinated pigs; the detection ability of the assay was comparable those of the PrioCHECK and UBI kits. There was 97.5, 93.4 and 66.6% agreement between the results obtained from our ELISA and those obtained from the PrioCHECK, UBI and CHEKIT kits, respectively. The kappa statistics were 0.95, 0.87 and 0.37, respectively. Moreover, antibodies for nonstructural proteins of the serotypes A, C, Asia 1, SAT 1, SAT 2 and SAT 3 were also detected in bovine sera. Furthermore, the absence of cross-reactions generated by different antibody titers against the swine vesicular disease virus and vesicular stomatitis virus (VSV) was also highlighted in this assay's specificit

2-[2-(4-Nitro­phenyl)hy­dra­zin­yl­idene]malononitrile

The title compound, C10H8N8, is close to planar (r.m.s. deviation from the mean plane = 0.118 Å). In the crystal, inversion dimers linked by pairs of N—H⋯N hydrogen bonds generate R 2 2(12) loops

Comparison of the use of prenatal care services and the risk of preterm birth between pregnant women with disabilities and those without disabilities: A nationwide cohort study

ObjectiveThe difficulties faced by pregnant women with disabilities in accessing health care may make them less likely to receive prenatal care. The aims of this study were to compare the number of prenatal services and the risk of preterm birth between pregnant women with and without disabilities.MethodsA total of 2999 pregnant women aged ≥20 years with birth records in 2011–2014 in Taiwan were enrolled. Data were obtained from the Registration File for Physical and Mental Disabilities and the National Health Insurance Research Database. A 1:4 matching between pregnant women with disabilities and those without disabilities was performed. The logistic regression analysis with generalized estimating equations was used to analyze.ResultsThe median of prenatal care services used by pregnant women with disabilities was 9.00 (interquartile range, IQR: 2.00). Pregnant women with disabilities used fewer services than those without disabilities (median, 10.00; IQR: 1.00). The disabled group (8.44%) had a significantly higher proportion of preterm births than did the non-disabled group (5.40%). The disabled group was at a 1.30 times higher risk of preterm births than was the non-disabled group.ConclusionsPregnant women with disabilities used significantly fewer prenatal care services and had a significantly higher risk of preterm birth than pregnant women without disabilities

Advanced age affects the outcome-predictive power of RIFLE classification in geriatric patients with acute kidney injury

The RIFLE (risk, injury, failure, loss, and end-stage) classification is widely used to gauge the severity of acute kidney injury, but its efficacy has not been formally tested in geriatric patients. To correct this we conducted a prospective observational study in a multicenter cohort of 3931 elderly patients (65 years of age or older) who developed acute kidney injury in accordance with the RIFLE creatinine criteria after major surgery. We studied the predictive power of the RIFLE classification for in-hospital mortality and investigated the potential interaction between age and RIFLE classification. In general, the survivors were significantly younger than the nonsurvivors and more likely to have hypertension. In patients 76 years of age and younger, RIFLE-R, -I, or -F classifications were significantly associated with increased hospital mortality in a stepwise manner. There was no significant difference, however, in hospital mortality in those over 76 years of age between patients with RIFLE-R and RIFLE-I, although RIFLE-F patients had significantly higher mortality than both groups. Thus, the less severe categorizations of acute kidney injury per RIFLE classification may not truly reflect the adverse impact on elderly patients

Distinct functional defect of three novel Brugada syndrome related cardiac sodium channel mutations

The Brugada syndrome is characterized by ST segment elevation in the right precodial leads V1-V3 on surface ECG accompanied by episodes of ventricular fibrillation causing syncope or even sudden death. The molecular and cellular mechanisms that lead to Brugada syndrome are not yet completely understood. However, SCN5A is the most well known responsible gene that causes Brugada syndrome. Until now, more than a hundred mutations in SCN5A responsible for Brugada syndrome have been described. Functional studies of some of the mutations have been performed and show that a reduction of human cardiac sodium current accounts for the pathogenesis of Brugada syndrome. Here we reported three novel SCN5A mutations identified in patients with Brugada syndrome in Taiwan (p.I848fs, p.R965C, and p.1876insM). Their electrophysiological properties were altered by patch clamp analysis. The p.I848fs mutant generated no sodium current. The p.R965C and p.1876insM mutants produced channels with steady state inactivation shifted to a more negative potential (9.4 mV and 8.5 mV respectively), and slower recovery from inactivation. Besides, the steady state activation of p.1876insM was altered and was shifted to a more positive potential (7.69 mV). In conclusion, the SCN5A channel defect related to Brugada syndrome might be diverse but all resulted in a decrease of sodium current