3,134 publications from this institution
Abstract Zero-dimensional nanostructures such as ZnO#ZnS QDs heterojunctures (QDHJs) are green nanoparticles and have gained a tremendous amount of attention. However, very little information is available on the effects of these heterojunctures on the transportation of drugs in blood. Herein, stilbenes were studied for their affinities for common bovine plasma proteins (CBPP) in the presence and absence of QDHJs with different diameters. The affinities of QDHJs for CBPP improved with increasing QDHJs size. QDHJs improved the affinities of resveratrol and polydatin for CBPP by 14.74% to 22.36% and 12.56% to 21.34% depending on the size of QDHJs. The number of binding sites (n) between resveratrol and polydatin for CBPP in the presence of QDHJs were 1.04 ± 0.03 and 1.06 ± 0.04, which were obviously higher than those in the absence of QDHJs (n = 0.89 and 0.92). QDHJs in blood will decrease the free concentration of stilbenes and weaken their pharmacological effects.
<b><i>Background:</i></b> Focal and segmental glomerulosclerosis (FSGS) is a clinical-pathologic condition marked by segmental and localized glomerular damages. Despite investigations, the molecular mechanisms behind FSGS development remain to be more clarified. By a comprehensive analysis of an FSGS-related array set, the aim of this study was to unravel the top pathways and molecules involved in the pathogenesis of this disorder. <b><i>Methods:</i></b> FSGS-related microarray dataset (GSE129973) from the Gene Expression Omnibus database was quality checked, analyzed, and its differentially expressed genes (DEGs) (log2 fold change &#x3e; 1) were used for the construction of a protein-protein interaction (PPI) network (STRING). The degree of centrality was considered to select the hub molecules in the network. The weighted gene co-expression network analysis (WGCNA) was utilized to construct co-expression modules. Hub molecules were selected based on module membership and gene significance values in the disease’s most correlated module. After spotting the key molecules considering both strategies, their expression pattern was checked in other FSGS microarray datasets. Gene ontology and Reactome pathway enrichment analyses were performed on the DEGs of the related module. <b><i>Results:</i></b> After quality checking, normalization, and analysis of the dataset, 5,296 significant DEGs, including 2,469 upregulated and 2,827 downregulated DEGs were identified. The WGCNA algorithm clustered the DEGs into nine independent co-expression modules. The disease most correlated module (black module) was recognized and considered for further enrichment analysis. The immune system, cell cycle, and vesicle-mediated transports were among the top enriched terms for the identified module’s DEGs. The immune system, cell cycle, and vesicle-mediated transports were among the top enriched terms for the black module’s DEGs. The key molecules (<i>BMP-2</i> and <i>COL4A1</i>) were identified as common hub molecules extracted from the two methods of PPI and the co-expressed networks. The two identified key molecules were validated in other FSGS datasets, where a similar pattern of expression was observed for both the genes. <b><i>Conclusions:</i></b> Two hub molecules (<i>BMP-2</i> and <i>COL4A</i>) and some pathways (vesicle-mediated transport) were recognized as potential players in the pathogenesis of FSGS.
Amlodipine, a calcium antagonist of the 1,4-dihydropyridine type, has been shown to be effective in reducing blood pressure (BP) throughout the day and night when given once daily. However, the potential chronopharmacologic differing effects on BP of amlodipine have only been addressed occasionally. We investigated the administration-time dependent antihypertensive efficacy of amlodipine in patients with essential hypertension. We studied 194 patients with grade 1–2 essential hypertension (101 men and 93 women), 55.3±12.1 years of age, randomly assigned to receive a single daily dose of amlodipine (5 mg/day) either upon awakening or at bedtime. BP was measured by ambulatory monitoring at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 hours before and after 3 months of therapy. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate the diurnal and nocturnal means of BP on a per subject basis. The BP reduction after 12 weeks of therapy with amlodipine was slightly but not significantly larger after bedtime dosing (10.4 and 7.3 mm Hg reduction in the 24-hour mean of systolic and diastolic BP after amlodipine on awakening; 11.5 and 7.0 mm Hg after bedtime dosing; P>0.463 for treatment-time effect). This BP reduction was similar during both daytime activity and nighttime resting hours, independently of dosing time, indicating a full 24-hour therapeutic coverage of amlodipine administered either on awakening or at bedtime. The day/night BP ratio (calculated as the nocturnal decline of BP relative to the diurnal mean) was slightly reduced for diastolic BP after morning treatment (-1.6, P=0.037), but remained unchanged after bedtime dosing of amlodipine (increase of 0.2 and 0.7 in systolic and diastolic BP, P>0.337). Results from this trial demonstrate that amlodipine efficiently reduces BP for the entire 24 hours of the day independently of the time of its administration with respect to the rest-activity cycle of each individual patient. The similar BP reduction observed for the diurnal and nocturnal BP means indicates that amlodipine does not modify the circadian pattern of BP variability, even if administered at bedtime.
Abstract We investigated the performance of two of the most popular differentiation‐based methods to detect loci under selection ( dfdist/fdist and bayescan ) in order to ascertain the average chromosome map distance between the detected outlier markers and the nearest loci under selection. We used a model of neutral markers genetically linked to selected loci (QTL) controlling a quantitative trait subject to divergent selection in two subpopulations connected by migration. The results are not particularly encouraging because for chromosome lengths above 0.5 morgan, at least 30% of outliers detected were positioned in chromosomes where QTL were absent, clearly denoting false positives. Outliers linked to QTL were on average closer to the nearest QTL than randomly chosen markers, but the methods showed a substantial uncertainty about the genetic association between markers and selected loci, as this association could be shown significantly only in a moderate number of replicates for most scenarios. At equal conditions, bayescan seemed to perform somewhat more efficiently than dfdist/fdist , with little difference between results for dominant and codominant markers.