A visco-hyperelastic constitutive approach for modeling polyvinyl alcohol sponge

This study proposes the quasi-linear viscoelastic (QLV) model to characterize the time dependent mechanical behavior of poly(vinyl alcohol) (PVA) sponges. The PVA sponges have implications in many viscoelastic soft tissues, including cartilage, liver, and kidney as an implant. However, a critical barrier to the use of the PVA sponge as tissue replacement material is a lack of sufficient study on its viscoelastic mechanical properties. In this study, the nonlinear mechanical behavior of a fabricated PVA sponge is investigated experimentally and computationally using relaxation and stress failure tests as well as finite element (FE) modeling. Hyperelastic strain energy density functions, such as Yeoh and Neo-Hookean, are used to capture the mechanical behavior of PVA sponge at ramp part, and viscoelastic model is used to describe the viscose behavior at hold part. Hyperelastic material constants are obtained and their general prediction ability is verified using FE simulations of PVA tensile experiments. The results of relaxation and stress failure tests revealed that Yeoh material model can define the mechanical behavior of PVA sponge properly compared with Neo-Hookean one. FE modeling results are also affirmed the appropriateness of Yeoh model to characterize the mechanical behavior of PVA sponge. Thus, the Yeoh model can be used in future biomechanical simulations of the spongy biomaterials. These results can be utilized to understand the viscoelastic behavior of PVA sponges and has implications for tissue engineering as scaffold.     

Polymorphism of killer cell immunoglobulin-like receptors (KIR) and their HLA ligands in Graves’ disease

Killer immunoglobulin-like receptors (KIR) play a pivotal role in commencement of both innate and adaptive immunity. Dysregulation of KIRs is associated with an increased risk of autoimmune disorders. This study was designed to assess whether polymorphisms in KIR gene family and their respective HLA class I ligands confer protection or susceptibly to Graves’ disease (GD). Eighty patients with confirmed GD (cases) and 176 healthy unrelated subjects (controls) were recruited. Using a polymerase chain reaction sequence-specific primer directed method (PCR-SSP), presence or absence of KIR genes and their HLA ligands were determined. No significant differences were observed between case and control groups regarding individual KIR gene frequencies (p > 0.05 in all cases). The frequency of group A haplotype (the most common KIR haplotype, encompassing 2DL1/2DL3/3DL1/2DS4/2DP1/3DP1/2DL4/3DL2/3DL3), was not different between individuals with and without GD. Moreover, among all other haplotypes (group Bx), no significant differences regarding distribution of centromeric and telomeric gene clusters were identifiable. Inhibitory/activatory gene contents were also comparable between the two groups. Four models of KIR-HLA interaction (inhibition, activation, unrestrained inhibition, and unrestrained activation) were constructed. No combination proved to confer susceptibility to, or offer protection against GD. It seems that the contribution of KIR gene polymorphism to natural killer cell dysfunction and other autoimmune abnormalities observed in GD is limited.     

Effects of Hippocampal Microinjection of Irisin,an Exercise-Induced Myokine,on Spatial and Passive Avoidance Learning and Memory in Male Rats

International Journal of Peptide Research and Therapeutics - Irisin is a soluble and exercise-induced myokine and/or adipokine hormone; generated by FNDC5 (a gene precursor) and also, it can...     

Compliance of bio-adhesive substrates controls the kinetics of membrane-substrate association

Mechanical stiffness of bio-adhesive substrates is one of the major regulators of the cell adhesion and migration. In this study, we propose a theoretical model for the spontaneous growth of focal adhesion (FA) sites, on compliant elastic substrates, at the early stages of cellular adhesion. Using a purely thermodynamic approach, we demonstrate that the rate of membrane-substrate association decreases with increasing the compliance of the substrate. This can be considered as a reason for smaller spread area of the FA points after the stabilization of adhesion on compliant substrates, as reported by experiments. We also show that the extent to which the compliance of the substrate modulates the growth rate of adhesion site depends on the areal density of cell-adhesive ligands on the substrate.     

Identification of a specific exosite on activated protein C for interaction with protease-activated receptor 1

Activated protein C (APC) is a vitamin K-dependent plasma serine protease which down-regulates the clotting cascade by inactivating procoagulant factors Va and VIIIa by limited proteolysis. In addition to its anticoagulant effect, APC also exhibits cytoprotective and antiinflammatory activity through the endothelial protein C receptor-dependent cleavage of protease activated receptor 1 (PAR-1) on endothelial cells. Recent mutagenesis data have indicated that the basic residues of two surface loops including those on 39 and the Ca2+-binding 70-80 loops constitute interactive sites for both factors Va and VIIIa, thereby mediating the interaction of APC specifically with these procoagulant cofactors. The basic residues of both loops have been discovered to be dispensable for the interaction of APC with PAR-1. It is not known if a similar exosite-dependent interaction contributes to the specificity of APC recognition of PAR-1 on endothelial cells. In this study, we have identified two acidic residues on helix-162 (Glu-167 and Glu-170) on the protease domain of APC which are required for the protease interaction with PAR-1, but not for its interaction with the procoagulant cofactors. Thus, the substitution of either Glu-167 or Glu-170 with Ala eliminated the cytoprotective signaling properties of APC without affecting its anticoagulant activity. These mutants provide useful tools for initiating in vivo studies to understand the extent to which the anticoagulant versus antiinflammatory activity of APC contributes to its beneficial effect in treating severe sepsis.     

Design,synthesis and biological evaluation of 6-(benzyloxy)-4-methylquinolin-2(1H)-one derivatives as PDE3 inhibitors

Selective PDE3 (phosphodiesterase 3) inhibitors improve cardiac contractility and may be used in congestive heart failure. However, their proarrhythmic potential is the most important side effect. In this work ten new synthetic compounds (3-[(4-methyl-2-oxo-1,2-dihydro-6-quinolinyl)oxy]methylbenzamide analogs: 4a–j) were designed, synthesized and tested for the inhibitory activity against human PDE3A and PDE3B. The strategy of the design was based on the structure of vesnarinone (a selective PDE3 inhibitor) and its docking analysis results. The synthetic compounds showed better PDE3 inhibitory activity in comparison with vesnarinone. Using docking analysis, a common binding model of each compound toward PDE3 was suggested. In the next step the potential cardiotonic activity of the best PDE3A inhibitors (4b, IC₅₀ = 0.43 ± 0.04 μM) was evaluated by using the spontaneously beating atria model. In the experiment, atrium of reserpine-treated rat was isolated and the contractile and chronotropic effects of the synthetic compound were assessed. That was carried out in comparison with vesnarinone. The best pharmacological profile was obtained for the compound 4b, which displayed selectivity for increasing the force of contraction (46 ± 3% change over the control) rather than the frequency rate (16 ± 4% change over the control) at 100 μM.     

Finite element simulation of an artificial intervertebral disk using fiber reinforced laminated composite model

Degeneration of intervertebral disk (IVD) has been increased in recent years. The lumbar herniation can be cured using conservative and surgical procedures. Surgery is considered after failure of conservative treatment. Partial discectomy, fusion, and total disk replacement (TDR) are also common surgical treatments for degenerative disk disease. However, due to limitations and disadvantages of the current treatments, many studies have been carried out to approach the best design of mimicking natural disk. Recently, a new method of TDRs has been introduced using nature deformation of IVD by reinforced fibers of annulus fibrosis. Nonetheless, owing to limitations of experimental works on the human body, numerical studies of IVD may help to understand load transfer and biomechanical properties within the disks with reinforced fibers. In this study, a three-dimensional (3D) finite element model of the L2-L3 disk vertebrae unit with 12 vertical fibers embedded into annulus fibrosis was constructed. The IVD was subjected to compressive force, bending moment, and axial torsion. The most important parameters of disk failures were compared to that of experimental data. The results showed that the addition of reinforced fibers into the disk invokes a significant decrease of stress in the nucleus and annulus. The findings of this study may have implications not only for developing IVDs with reinforced fibers but also for the application of fiber reinforced IVD in orthopedics surgeries as a suitable implant.     

Effects of Influenza Derived Peptide on CD8 T Cell Responses to MHC Class I-Restricted Human Telomerase Reverse Transcriptase (hTERT)-Derived Peptide

International Journal of Peptide Research and Therapeutics - Tumor cells in breast cancer are immunogenic and express proteins that can induce immune responses. One important antigen is human...     

Long-term storage of sexual and asexual Trichogramma brassicae (Hymenoptera: Trichogrammatidae)

The effect of exposure duration to pre-storage (representing fall conditions) and storage (representing winter conditions) temperatures on the emergence rate in sexual and asexual Trichogramma brassicae Bezdenko (Hymenoptera: Trichogrammatidae) was studied under controlled laboratory conditions. Asexual T. brassicae was infected by Wolbachia, an endosymbiont bacterium. We considered 0, 30, 40, 50 and 60 days as exposure duration at 10°C and 0, 30, 60, 90 followed by 180 days as exposure duration at 4°C for both T. brassicae strains. Emergence rate was significantly affected by the presence of Wolbachia, the duration of exposure to 10°C, the duration of storage at 4°C and their interactions, but not by the interaction between strain × storage duration at 4°C. Emergence rate of adults was positively correlated with exposure duration at 10°C, but it gradually decreased as the cold storage duration (4°C) increased in both strains. In conclusion, we are able to store both asexual and sexual strains for longer periods of time at 4°C, but the emergence rate of sexual T. brassicae was greater than asexual in all the treatments. The presence of Wolbachia could have a negative effect on fitness of T. brassicae and reduces its emergence rate after long-term storage.