In searching for alternative ways to reduce or inhibit amyloid formation, we have studied this process using hen egg white lysozyme (HEWL) in the presence of a low concentration of protic ionic liquids. The ionic liquids were synthesized in a combinatorial fashion maintaining the cationic part (tetramethylguanidinium) with alteration of the anionic component of each compound tested. It was observed that one of these compounds (tetramethylguanidinium acetate) inhibited amyloid formation of HEWL in vitro by nearly 50%. Examination under transmission electron microscopy confirmed the fibril inhibition, and fibrils were observed to be morphologically thinner. To investigate the mechanism of inhibition, intrinsic fluorescence, ANS binding, and circular dichroism analyses were performed. These analyses indicated that the native structure of HEWL was maintained in the presence of the ionic liquid. Performing native PAGE and nondenaturing agarose electrophoresis, it became evident that some of the intermediate oligomers were not converted to protofibrils and that the oligomers were trapped in more stable conformations. Additionally, it was observed that this inhibitory effect was related to the ionic liquid itself and not the solvated ions. It also became evident that the carboxyl functional group was important in the inhibition. The size of the anions and kosmotropicity did not play significant roles in the fibril inhibition.
Cell separation is a key step in many biomedical research areas including biotechnology, cancer research, regenerative medicine, and drug discovery. While conventional cell sorting approaches have led to high‐efficiency sorting by exploiting the cell's specific properties, microfluidics has shown great promise in cell separation by exploiting different physical principles and using different properties of the cells. In particular, label‐free cell separation techniques are highly recommended to minimize cell damage and avoid costly and labor‐intensive steps of labeling molecular signatures of cells. In general, microfluidic‐based cell sorting approaches can separate cells using “intrinsic” (e.g., fluid dynamic forces) versus “extrinsic” external forces (e.g., magnetic, electric field, etc.) and by using different properties of cells including size, density, deformability, shape, as well as electrical, magnetic, and compressibility/acoustic properties to select target cells from a heterogeneous cell population. In this work, principles and applications of the most commonly used label‐free microfluidic‐based cell separation methods are described. In particular, applications of microfluidic methods for the separation of circulating tumor cells, blood cells, immune cells, stem cells, and other biological cells are summarized. Computational approaches complementing such microfluidic methods are also explained. Finally, challenges and perspectives to further develop microfluidic‐based cell separation methods are discussed.
In this paper, a distributed parameter model is used to study the pull-in instability of cantilever type nanomechanical switches subjected to intermolecular and electrostatic forces. In modeling of the electrostatic force, the fringing field effect is taken into account. The model is nonlinear due to the inherent nonlinearity of the intermolecular and electrostatic forces. The nonlinear differential equation of the model is transformed into the integral form by using the Green's function of the cantilever beam. Closed-form solutions are obtained by assuming an appropriate shape function for the beam deflection to evaluate the integrals. The pull-in parameters of the switch are computed under the combined effects of electrostatic and intermolecular forces. Electrostatic microactuators and freestanding nanoactuators are considered as special cases of our study. The detachment length and the minimum initial gap of freestanding nano-cantilevers, which are the basic design parameters for NEMS switches, are determined. The results of the distributed parameter model are compared with the lumped parameter model.
Spironolactone (SP) known as an anti-androgen drug, has been proven to be effective in treatment of acne. The quest to minimize the unnecessary systemic side effects associated with the oral drug administration of spironolactone, has led to a growing interest of loading SP on lipid nanoparticles to deliver the drug in a topical formulation. The aim of the current investigation was to prepare and compare the performance of SP loaded nanostructured lipid carrier (SP-NLC) and SP alcoholic gels (SP-ALC) on two groups of respective patient populations, group A and group B in the treatment of mild to moderate acne vulgaris. The results showed that SP-NLCs were spherical in shape with an average diameter of ∼240nm. The polydispersity index (PI) and zeta potential of these nanoparticles were 0.286 and -21.4 respectively. The gels showed non-Newtonian independent pseudoplastic and shear thinning behavior. The SP-NLCs was not toxic to fibroblast cell strains at the 24 and 48h periods. Results showed that the mean number of total lesions (37.66±9.27) and non-inflammatory lesions (29.26±7.99) in group A significantly decreased to 20.31±6.58 (p<0.05) and to 13.95±5.22 (p<0.05) respectively. A similar pattern was observed for group B where the mean number of total lesions and non-inflammatory lesions reduced from 33.73±9.40 to 19.13±5.53 (p<0.05) and from 25.65±8.12 to 13.45±4.48 (p<0.05) respectively. The total lesion count (TLC) was significantly decreased from 37.16±9.28 to 19.63±6.36 (for group A; p<0.071) and 32.60±9.32 to 18.33±5.55 (for group B; p<0.05) respectively. After treatment with SP-NLC for 8 weeks, the water content of the skin significantly (p<0.05) increased from 37.44±8.85 to 45.69±19.34 instrumental units. Therefore, the SP-NLC gel may help in controlling acne vulgaris with skin care benefits.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.