Anti-inflammatory and antioxidant properties of HDLs are impaired in type 2 diabetes.

ObjectiveIn mice, 4F, an apolipoprotein A-I mimetic peptide that restores HDL function, prevents diabetes-induced atherosclerosis. We sought to determine whether HDL function is impaired in type 2 diabetic (T2D) patients and whether 4F treatment improves HDL function in T2D patient plasma in vitro.Research design and methodsHDL anti-inflammatory function was determined in 93 T2D patients and 31 control subjects as the ability of test HDLs to inhibit LDL-induced monocyte chemotactic activity in human aortic endothelial cell monolayers. The HDL antioxidant properties were measured using a cell-free assay that uses dichlorofluorescein diacetate. Oxidized fatty acids in HDLs were measured by liquid chromatography-tandem mass spectrometry. In subgroups of patients and control subjects, the HDL inflammatory index was repeated after incubation with L-4F.ResultsThe HDL inflammatory index was 1.42 ± 0.29 in T2D patients and 0.70 ± 0.19 in control subjects (P < 0.001). The cell-free assay was impaired in T2D patients compared with control subjects (2.03 ± 1.35 vs. 1.60 ± 0.80, P < 0.05), and also HDL intrinsic oxidation (cell-free assay without LDL) was higher in T2D patients (1,708 ± 739 vs. 1,233 ± 601 relative fluorescence units, P < 0.001). All measured oxidized fatty acids were significantly higher in the HDLs of T2D patients. There was a significant correlation between the cell-free assay values and the content of oxidized fatty acids in HDL fractions. L-4F treatment restored the HDL inflammatory index in diabetic plasma samples (from 1.26 ± 0.17 to 0.71 ± 0.11, P < 0.001) and marginally affected it in healthy subjects (from 0.81 ± 0.16 to 0.66 ± 0.10, P < 0.05).ConclusionsIn patients with T2D, the content of oxidized fatty acids is increased and the anti-inflammatory and antioxidant activities of HDLs are impaired

Abnormal systolic blood pressure response during exercise is related to subendocardial hypoperfusion detected by exercise 201Tl myocardial scintigraphy in patient with hypertrophic cardiomyopathy

Balcells, EugèniaPla general, d'alguns dels elements que formen la taula periòdica. Cadascun dels 112 elements és representat pel seu espectre de color. Es van produir diverses còpies de l'obra, aquesta està a la Biblioteca de la Facultat de Química

Role of the imprinted allele of the Cdkn1c gene in mouse neocortical development

Imprinted genes are expressed from only one allele in a parent of origin–specific manner. The cyclin-dependent kinase inhibitor p57^{kip2} is encoded by an imprinted gene Cdkn1c, with the paternal allele being silenced. The possible expression and function of the paternal allele of Cdkn1c have remained little studied, however. We now show that the paternal allele of the Cdkn1c gene is expressed at a low level in the developing mouse neocortex. Surprisingly, the central nervous system-specific conditional deletion of the paternal allele (pat cKO) at the Cdkn1c locus resulted in a marked reduction in brain size. Furthermore, pat cKO gradually reduced the number of neural stem-progenitor cells (NPCs) during neocortical development, and thus reduced the number of upper-layer neurons, which were derived from late-stage NPCs. Our results thus show that the paternal allele of the Cdkn1c locus plays a key role in maintenance of NPCs during neocortical development

Structural and Functional Vocal Fold Epithelial Integrity Following Injury

Objectives/Hypothesis: An intact epithelium is an important part of vocal fold defense. Damage to the epithelium can compromise vocal fold homeostasis and protection of the host tissue from viral and bacterial invasion. Elucidating the effects of damage on epithelial architectural and barrier integrity provides insight into the role of epithelium in protecting vocal folds. Using an animal model, we evaluated the time course of structural and functional epithelial restoration following injury. Study Design: Prospective, controlled animal study. Methods: Forty rats underwent surgery to remove vocal fold mucosa unilaterally. Larynges were harvested at five time intervals between 3 to 90 days postinjury and were prepared for histological and permeability analyses. Results: Rapid restoration of structural integrity was demonstrated by return of a multilayerd epithelium, intercellular junctions, and basement membrane at 5 days postinjury. Atypical epithelial permeability was observed up to 5 weeks postinjury. Conclusion: Restoration of epithelial barrier integrity lags epithelial structural restoration. Consequently, epithelial regeneration cannot be equated with return of functional barrier integrity. Rather, ongoing leakiness of regenerated epithelium indicates that vocal folds remain at risk for damage, pathogen invasion, and remodeling postinjury

Apolipoprotein A-I Mimetic Peptides Prevent Atherosclerosis Development and Reduce Plaque Inflammation in a Murine Model of Diabetes

ObjectiveTo determine the effect of the apolipoprotein A-I (ApoA-I) mimetic peptide, D-4F, on atherosclerosis development in a pre-existing diabetic condition.Research design and methodsWe induced hyperglycemia in 6-week-old apoE(-/-) female mice using streptozotocin. Half of the diabetic apoE(-/-) mice received D-4F in drinking water. Ten weeks later, plasma lipids, glucose, insulin levels, atherosclerotic lesions, and lesion macrophage content were measured.ResultsDiabetic apoE(-/-) mice developed ∼300% more lesion area, marked dyslipidemia, increased glucose levels, and reduced plasma insulin levels when compared with nondiabetic apoE(-/-) mice. Atherosclerotic lesions were significantly reduced in the D-4F-treated diabetic apoE(-/-) mice in whole aorta (1.11 ± 0.73 vs. 0.58 ± 0.44, percentage of whole aorta, P < 0.01) and in aortic roots (36,038 ± 18,467 μm²/section vs. 17,998 ± 12,491 μm²/section, P < 0.01) when compared with diabetic apoE(-/-) mice that did not receive D-4F. Macrophage content in atherosclerotic lesions from D-4F-treated diabetic apoE(-/-) mice was significantly reduced when compared with nontreated animals (78.03 ± 26.1 vs. 29.6 ± 15.2 P < 0.001, percentage of whole plaque). There were no differences in glucose, insulin, total cholesterol, HDL cholesterol, and triglyceride levels between the two groups. Arachidonic acid, PGE₂, PGD₂, 15-HETE, 12-HETE, and 13-HODE concentrations were significantly increased in the liver tissue of diabetic apoE(-/-) mice compared with nondiabetic apoE(-/-) mice and significantly reduced by D-4F treatment.ConclusionsOur results suggest that oral D-4F can prevent atherosclerosis development in pre-existing diabetic mice and this is associated with a reduction in hepatic arachidonic acid and oxidized fatty acid levels

FKF1 conveys timing information for CONSTANS stabilization in photoperiodic flowering

Plants use day-length information to coordinate flowering time with the appropriate season to maximize reproduction. In Arabidopsis, the long-day specific expression of CONSTANS (CO) protein is crucial for flowering induction. Although light signaling regulates CO protein stability, the mechanism by which CO is stabilized in the long-day afternoon has remained elusive. Here we demonstrate that FLAVIN-BINDING, KELCH REPEAT, F-BOX 1 (FKF1) protein stabilizes CO protein in the afternoon in long days. FKF1 interacts with CO through its LOV domain, and blue light enhances this interaction. In addition, FKF1 simultaneously removes CYCLING DOF FACTOR 1 (CDF1) that represses CO and FLOWERING LOCUS T (FT) transcription. Together with CO transcriptional regulation, FKF1 protein controls robust FT mRNA induction through multiple feedforward mechanisms that accurately control flowering timing