Construction of chrysophanol loaded nanoparticles with N-octyl-O-sulfate chitosan for enhanced nephroprotective effect.

Natural occurring anthraquinone like chrysophanol has been studied because of its anti-diabetic, anti-tumor, anti-inflammatory, hepatoprotective and neuroprotective properties. Nonetheless, its poor water solubility and unstable nature are big concerns in achieving efficient delivery and associated pharmacokinetic and pharmacodynamic effects. Herein, this study sought to solve the above-mentioned problem through development of chrysophanol-loaded nanoparticles to enhance the bioavailability of chrysophanol and to evaluate its anti-renal fibrosis effect in rats. After synthesis of a safe N-octyl-O-sulfate chitosan, we used it to prepare chrysophanol-loaded nanoparticles through dialysis technique before we performed and physical characterization. Also, we tested the stability of the nanoparticles for 21 days at 4 °C and room temperature (25 °C) and evaluated their pharmacokinetics and anti-renal fibrosis effect in rat model of chronic kidney disease (CKD). In terms of results, the nano-preparation demonstrated an acceptable narrow size distribution, wherein the encapsulation rate, size, polydispersed index (PDI) and electrokinetic potential at room temperature were respectively 83.41±0.89 %, 364.88±13.62 nm, 0.192±0.015 and 23.78±1.39 mV. During 21 days of storage, we observed that size of particles and electrokinetic potential altered slightly but the difference was statistically insignificant (p > 0.05). Also, in vitro release studies showed that the formulation reached 84.74 % at 24 h. Chrysophanol nanoparticles showed a 2.57-fold increase in bioavailability compared to unformulated chrysophanol. More importantly, chrysophanol nanoparticles demonstrated certain renal internalization properties and anti-renal fibrosis effects, which could ultimately result in reduced blood-urea nitrogen (BUN), kidney-injury molecule-1 (KIM-1) and serum creatinine (SCr) levels in model rats. In conclusion, the prepared chrysophanol-loaded nanoparticles potentially increased bioavailability and enhanced nephroprotective effects of chrysophanol.

Detection of 3D Arterial Centerline Extraction in Spiral CT Coronary Angiography.

This paper presents an in-depth study and analysis of the 3D arterial centerline in spiral CT coronary angiography, and constructs its detection and extraction technique. The first time, the distance transform is used to complete the boundary search of the original figure; the second time, the distance transform is used to calculate the value of the distance transform of all voxels, and according to the value of the distance transform, unnecessary voxels are deleted, to complete the initial contraction of the vascular region and reduce the computational consumption in the next process; then, the nonwitnessed voxels are used to construct the maximum inner joint sphere model and find the skeletal voxels that can reflect the shape of the original figure. Finally, the skeletal lines were optimized on these initially extracted skeletal voxels using a dichotomous-like principle to obtain the final coronary artery centerline. Through the evaluation of the experimental results, the algorithm can extract the coronary centerline more accurately. In this paper, the segmentation method is evaluated on the test set data by two kinds of indexes: one is the index of segmentation result evaluation, including dice coefficient, accuracy, specificity, and sensitivity; the other is the index of clinical diagnosis result evaluation, which is to refine the segmentation result for vessel diameter detection. The results obtained in this paper were compared with the physicians' labeling results. In terms of network performance, the Dice coefficient obtained in this paper was 0.89, the accuracy was 98.36%, the sensitivity was 93.36%, and the specificity was 98.76%, which reflected certain advantages in comparison with the advanced methods proposed by previous authors. In terms of clinical evaluation indexes, by performing skeleton line extraction and diameter calculation on the results obtained by the segmentation method proposed in this paper, the absolute error obtained after comparing with the diameter of the labeled image was 0.382 and the relative error was 0.112, which indicates that the segmentation method in this paper can recover the vessel contour more accurately. Then, the results of coronary artery centerline extraction with and without fine branch elimination were evaluated, which proved that the coronary artery centerline has higher accuracy after fine branch elimination. The algorithm is also used to extract the centerline of the complete coronary artery tree, and the results prove that the algorithm has better results for the centerline extraction of the complete coronary vascular tree.

Comprehensive Analysis of Pertinent Genes and Pathways in Atrial Fibrillation.

PURPOSE: Atrial fibrillation (AF) is the most frequent arrhythmia in clinical practice. The pathogenesis of AF is not yet clear. Therefore, exploring the molecular information of AF displays much importance for AF therapy. METHODS: The GSE2240 data were acquired from the Gene Expression Omnibus (GEO) database. The R limma software package was used to screen DEGs. Based on the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) databases, we conducted the functions and pathway enrichment analyses. Then, the STRING and Cytoscape software were employed to build Protein-Protein Interaction (PPI) network and screen for hub genes. Finally, we used the Cell Counting Kit-8 (CCK-8) experiment to explore the effect of hub gene knockdown on the proliferation of AF cells. RESULT: 906 differentially expressed genes (DEGs), including 542 significantly upregulated genes and 364 significantly downregulated genes, were screened in AF. The genes of AF were mainly enriched in vascular endothelial growth factor-activated receptor activity, alanine, regulation of histone deacetylase activity, and HCM. The PPI network constructed of significantly upregulated DEGs contained 404 nodes and 514 edges. Five hub genes, ASPM, DTL, STAT3, ANLN, and CDCA5, were identified through the PPI network. The PPI network constructed by significantly downregulated genes contained 327 nodes and 301 edges. Four hub genes, CDC42, CREB1, AR, and SP1, were identified through this PPI network. The results of CCK-8 experiments proved that knocking down the expression of CDCA5 gene could inhibit the proliferation of H9C2 cells. CONCLUSION: Bioinformatics analyses revealed the hub genes and key pathways of AF. These genes and pathways provide information for studying the pathogenesis, treatment, and prognosis of AF and have the potential to become biomarkers in AF treatment.

Rosuvastatin improves myocardial hypertrophy after hemodynamic pressure overload via regulating the crosstalk of Nrf2/ARE and TGF-ß/ smads pathways in rat heart.

Left ventricular hypertrophy is more commonly associated with hemodynamic overload imposed by hypertension or volume overload. Transforming growth factor ß (TGF-ß) is involved in the cardiac hypertrophy and fibrosis of the left ventricle. The fact that TGF-ß1 and the nuclear factor erythroid 2-related factor 2 (Nrf2) both become up-regulated upon persistent vessel overload suggests that these two factors may virtually impact on their signaling pathways. In this research, 40 rats were divided into sham group, model group, rosuvastatin low and high dose group. Rat models were established by incomplete constriction of abdominal aorta. After five weeks treatment, blood pressure, heart mass index (HMI), hemodynamic parameters and the average diameter of myocardium cell and collagen volume fraction (CVF) improved significantly in rosuvastatin groups, compared with the model group. Both rosuvastatin groups, increased in expression of Smad7, Nrf2, NAD (P) H dehydrogenase [quinone] 1 (Nqo1) and heme oxygenase 1(Ho1),and decreased in expression of TGF-ßl、Smad3 compared with the model group. Results from co-immunoprecipitation and GST pull down showed that Nrf2 interacts with Smad7. Our results revealed the crosstalk between TGF-ß1/Smads and Nrf2/ antioxidant response elements (ARE) pathways in myocardial remodeling through the interaction between Smad7 and Nrf2. Rosuvastatin can improve cardiac function and hypertrophy by regulating the crosstalk of the two signaling pathways.