Residual stress and circumferential stress distribution in a finite element model of the arterial wall

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Residual stress distribution in a lamellar model of the arterial wall

Excessive wall circumferential stress in arteries caused by luminal pressure leads to endothelial damage and clinical consequences. In addition to circumferential stress, arterial wall contains residual stress with compressive and tensile components on intima and adventitia sides. The intimal compressive component compensates part of tensile stress induced by blood pressure, hence reduces severity of endothelial tension. The opening angle caused by radial cut of arterial ring defines residual stress. In this study, finite element modelling is used to evaluate residual stress in a lamellar model of human aorta with differing opening angle and elastic modulus. Results show non-linear residual stress profiles across wall thickness, influenced by structural and mechanical parameters. Elevation of opening angle from 50° to 90° leads to increase of intimal compressive component compensating up to 32.6% of the pressure-induced tensile stress. Results may be applied in study of endothelial injury caused by excessive stress in situations such as aging, hypertension and atherosclerosis.7 page(s

Investigation on Amount of Secreted Nitric Oxide from Endothelial Cells by Applying Shear Stress and Different Temperature

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Development of Delivery Systems Enhances the Potency of Cell-Based HIV-1 Therapeutic Vaccine Candidates

An effective therapeutic vaccine to eradicate HIV-1 infection does not exist yet. Among different vaccination strategies, cell-based vaccines could achieve in clinical trials. Cell viability and low nucleic acid expression are the problems related to dendritic cells (DCs) and mesenchymal stem cells (MSCs), which are transfected with plasmid DNA. Thus, novel in vitro strategies are needed to improve DNA transfection into these cells. The recent study assessed immune responses generated by MSCs and DCs, which were derived from mouse bone marrow and modified with Nef antigen using novel methods in mice. For this purpose, an excellent gene transfection approach by mechanical methods was used. Our data revealed that the transfection efficacy of Nef DNA into the immature MSCs and DCs was improved by the combination of chemical and mechanical (causing equiaxial cyclic stretch) approaches. Also, chemical transfection performed two times with 48-hour intervals further increased gene expression in both cells. The groups immunized with Nef DC prime/rNef protein boost and then Nef MSC prime/rNef protein boost were able to stimulate high levels of IFN-γ, IgG2b, IgG2a, and Granzyme B directed toward Th1 responses in mice. Furthermore, the mesenchymal or dendritic cell-based immunizations were more effective compared to protein immunization for enhancement of the Nef-specific T-cell responses in mice. Hence, the use of chemical reagent and mechanical loading simultaneously can be an excellent method in delivering cargoes into DCs and MSCs. Moreover, DC- and MSC-based immunizations can be considered as promising approaches for protection against HIV-1 infections

Nitric oxide secretion by endothelial cells in response to fluid shear stress, aspirin, and temperature

Current vascular grafts have a high incidence of failure, especially in the grafts less than 6 mm in diameter, due to thrombus formation. Nitric oxide (NO) is released by endothelium and has some beneficial influences such as an antithrombotic effect. We hypothesized that applying different shear stress regiments and low temperature or aspirin would result in an increase in the amount of NO release from human umbilical vein endothelial cells (HUVECs) and decrease in platelet aggregation in the same manner as expected in vivo. HUVECs were cultured into the intraluminal surface of silicone tubes. HUVECs were subjected for 60 min to different parameters of shear stress, temperature, aspirin, and platelets or a combination in a perfusion bioreactor by monitoring NO secretion. We found that shear stress leads to an elevation of NO production in HUVECS, independent of the shear stress magnitude (0.9 or 1.8 dyne/cm2). The magnitude of this response increased with a decrease in temperature. Our results also show that by addition of platelets in combination with aspirin to media circulation, no thrombus formation occurred during the test time. Presence of aspirin resulted in marked increase in NO levels. In conclusion, shear stresses, temperature lowering, and aspirin increase the amount of NO release from HUVECs. Also no thrombus formation was detected in our experimental setting

Enhanced gene delivery in tumor cells using chemical carriers and mechanical loadings.

Intracellular delivery of DNA is considered a challenge in biological research and treatment of diseases. The previously reported transfection rate by commercially available transfection reagents in cancer cell lines, such as the mouse lung tumor cell line (TC-1), is very low. The purpose of this study is to introduce and optimize an efficient gene transfection method by mechanical approaches. The combinatory transfection effect of mechanical treatments and conventional chemical carriers is also investigated on a formerly reported hard-to-transfect cell line (TC-1). To study the effect of mechanical loadings on transfection rate, TC-1 tumor cells are subjected to uniaxial cyclic stretch, equiaxial cyclic stretch, and shear stress. The TurboFect transfection reagent is exerted for chemical transfection purposes. The pEGFP-N1 vector encoding the green fluorescent protein (GFP) expression is utilized to determine gene delivery into the cells. The results show a significant DNA delivery rate (by ~30%) in mechanically transfected cells compared to the samples that were transfected with chemical carriers. Moreover, the simultaneous treatment of TC-1 tumor cells with chemical carriers and mechanical loadings significantly increases the gene transfection rate up to ~ 63% after 24 h post-transfection. Our results suggest that the simultaneous use of mechanical loading and chemical reagent can be a promising approach in delivering cargoes into cells with low transfection potentials and lead to efficient cancer treatments