Chrysin,Apigenin and Acacetin Inhibit Tumor Necrosis Factor-Related Apoptosis—Inducing Ligand Receptor-1 (TRAIL-R1) on Activated RAW264.7 Macrophages

Expression level of Tumor Necrosis Factor—related apoptosis—inducing ligand (TRAIL) receptors is one of the most important factors of TRAIL-mediated apoptosis in cancer cells. We here report for the first time data concerning TRAIL-R1 and TRAIL-R2 receptor expression on RAW264.7 macrophages. Three substances belonging to flavones: chrysin, apigenin and acacetin which differ from their substituents at the 4'' position in the phenyl ring were used in assays because of the variety of biological activities (e.g., anticancer activity) of the polyphenol compounds. The expression of TRAIL-R1 and TRAIL-R2 death receptors on non-stimulated and LPS (lipopolysaccharide)-stimulated macrophages was determined using flow cytometry. We demonstrate that RAW264.7 macrophages exhibit TRAIL-R1 surface expression and that the tested compounds: chrysin, apigenin and acacetin can inhibit TRAIL-R1 death receptor expression level on macrophages.     

Optimal charging strategy design for lithium‐ion batteries considering minimization of temperature rise and energy loss

Battery charging techniques are critical to enhance battery operation performance. Charging temperature rise, energy loss, and charging time are three key indicators to evaluate charging performance. It is imperative to decrease temperature rise and energy loss without extending the charging time during the charging process. To this end, an equivalent circuit electrical model, a power loss model, and a thermal model are built in this study for lithium‐ion batteries. Then, an integrated objective function is formulated to minimize energy loss and temperature increment during battery charging. To further validate the generality and feasibility of the proposed charging strategy, experiments are conducted with respect to different current, operating temperatures, battery types, and aging status. Comparison results demonstrate that the devised charging strategy is capable of achieving the intended effect under any operating temperature and with different aging status.     

MicroRNA expression profile and lipid metabolism characteristics in liver of rat undergoing high-fat diet

This study aimed to investigate the microRNA expression profile and the characteristics of lipid metabolism in the livers of rats undergoing a high-fat diet. Fifty male Sprague-Dawley (SD) rats were divided into a standard chow group (C group, N = 10) and a high-fat diet group (H group, N = 40). After 12 weeks, the rat body weight, body length, fat mass, and serum lipid concentration were measured. The expression profile of microRNAs and the gene and protein expression levels involved in lipid metabolism in rat liver were detected. Body fat and serum lipid concentrations were all significantly higher in the H group than those in the C group (p < 0.05 or p < 0.01). The expression of 10 microRNAs showed significant differences in the liver (p < 0.05). In particular, the let-7 family expression levels significantly increased (p < 0.05) in the H group compared with those in the C group. Compared with the C group, the high-fat diet resulted in low FAS, CPT1A, and ApoAI mRNA expression levels (p < 0.05 or p < 0.01) and high PPARα and FAT/CD36 mRNA expression levels in the H group rat liver (p < 0.01). Meanwhile, the protein PPARα, FAS, CPT1A, FAT/CD36, and ApoAI expression levels were all significantly lower in the H group than those in the C group (p < 0.05 or p < 0.01). In conclusion, the high-fat diet increased the body fat and serum lipid levels and altered the 10 microRNA expression levels in the liver. The high-fat diet may affect hepatic carbohydrate metabolism and increase ectopic fat accumulation through let-7 family overexpression. The high-fat diet for 12 weeks decreased lipid metabolism level in the liver, thereby decreasing fatty acid synthesis, oxidation, and transport by down-regulating the PPARα, FAS, CPT1A, FAT/CD36, and ApoAI protein levels.     

Improving cytocompatibility of Co28Cr6Mo by TiO2 coating: gene expression study in human endothelial cells

Cobalt-based materials are widely used for coronary stents, as well as bone and joint implants. However, their use is associated with high corrosion incidence. Titanium alloys, by contrast, are more biocompatible owing to the formation of a relatively inactive titanium oxide (TiO₂) layer on their surface. This study was aimed at improving Co28Cr6Mo alloy cytocompatibility via sol–gel TiO₂ coating to reduce metal corrosion and metal ion release. Owing to their role in inflammation and tissue remodelling around an implant, endothelial cells present a suitable in vitro model for testing the biological response to metallic materials. Primary human endothelial cells seeded on Co28Cr6Mo showed a stress phenotype with numerous F-actin fibres absent on TiO₂-coated material. To investigate this effect at the gene expression level, cDNA microarray analysis of in total 1301 genes was performed. Compared with control cells, 247 genes were expressed differentially in the cells grown on Co28Cr6Mo, among them genes involved in proliferation, oxidative stress response and inflammation. TiO₂ coating reduced the effects of Co28Cr6Mo on gene expression in endothelial cells, with only 34 genes being differentially expressed. Quantitative real-time polymerase chain reaction and protein analysis confirmed microarray data for selected genes. The effect of TiO₂ coating can be, in part, attributed to the reduced release of Co²⁺, because addition of CoCl₂ resulted in similar cellular responses. TiO₂ coating of cobalt-based materials, therefore, could be used in the production of cobalt-based devices for cardiovascular and skeletal applications to reduce the adverse effects of metal corrosion products and to improve the response of endothelial and other cell types.     

Porous hydroxyapatite and biphasic calcium phosphate ceramics promote ectopic osteoblast differentiation from mesenchymal stem cells

Abstract

Because calcium phosphate (Ca–P) ceramics have been used as bone substitutes, it is necessary to investigate what effects the ceramics have on osteoblast maturation. We prepared three types of Ca–P ceramics with different Ca–P ratios, i.e. hydroxyapatite (HA), beta-tricalcium phosphate (β-TCP), and biphasic calcium phosphate (BCP) ceramics with dense-smooth and porous structures. Comprehensive gene expression microarray analysis of mouse osteoblast-like cells cultured on these ceramics revealed that porous Ca–P ceramics considerably affected the gene expression profiles, having a higher potential for osteoblast maturation. In the in vivo study that followed, porous Ca–P ceramics were implanted into rat skeletal muscle. Sixteen weeks after the implantation, more alkaline-phosphatase-positive cells were observed in the pores of hydroxyapatite and BCP, and the expression of the osteocalcin gene (an osteoblast-specific marker) in tissue grown in pores was also higher in hydroxyapatite and BCP than in β-TCP. In the pores of any Ca–P ceramics, 16 weeks after the implantation, we detected the expressions of marker genes of the early differentiation stage of chondrocytes and the complete differentiation stage of adipocytes, which originate from mesenchymal stem cells, as well as osteoblasts. These marker gene expressions were not observed in the muscle tissue surrounding the implanted Ca–P ceramics. These observations indicate that porous hydroxyapatite and BCP had a greater potential for promoting the differentiation of mesenchymal stem cells into osteoblasts than β-TCP.     

Designing experiments to understand the variability in biochemical reaction networks

Exploiting the information provided by the molecular noise of a biological process has proved to be valuable in extracting knowledge about the underlying kinetic parameters and sources of variability from single-cell measurements. However, quantifying this additional information a priori, to decide whether a single-cell experiment might be beneficial, is currently only possible in systems where either the chemical master equation is computationally tractable or a Gaussian approximation is appropriate. Here, we provide formulae for computing the information provided by measured means and variances from the first four moments and the parameter derivatives of the first two moments of the underlying process. For stochastic kinetic models for which these moments can be either computed exactly or approximated efficiently, the derived formulae can be used to approximate the information provided by single-cell distribution experiments. Based on this result, we propose an optimal experimental design framework which we employ to compare the utility of dual-reporter and perturbation experiments for quantifying the different noise sources in a simple model of gene expression. Subsequently, we compare the information content of a set of experiments which have been performed in an engineered light-switch gene expression system in yeast and show that well-chosen gene induction patterns may allow one to identify features of the system which remain hidden in unplanned experiments.     

Treating Arterial Ageing in Patients with Diabetes: From Mechanisms to Effective Drugs

Diabetes mellitus is a major healthcare problem. It is not only characterized by hyperglycemia and chronic complications, but in longer lasting diabetes and a longer living population, it is also associated with accelerated arterial ageing, which importantly contributes to cardiovascular complications. The accelerated arterial ageing in patients with diabetes should be considered separately from arterial ageing in patients without diabetes. Basic and clinical research have allowed better insight into the mechanisms of arterial ageing. In a simplified mechanistic way, it could be considered that the three tightly connected cornerstone characteristics of arterial ageing in patients with diabetes are: phenotypic presentation as endothelial dysfunction and arterial stiffness, and the underlying basic ageing-facilitating mechanism represented as the impaired expression of genetic longevity pathways. Currently, specific drugs for preventing/treating arterial ageing are not available. Therefore, we aimed to review the capacity of available drugs, particularly antidiabetic drugs, to interfere with the arterial ageing process. In the near future, these characteristics could help to guide therapy in patients with diabetes. Overall, it appears that arterial ageing could become a new target in diabetes. The expanding knowledge regarding the capability of antidiabetic drugs and other available drugs to inhibit/delay arterial aging is therefore essential.