Aldose Reductase Inhibition Prevents Allergic Airway Remodeling through PI3K/AKT/GSK3β Pathway in Mice

Background

Long-term and unresolved airway inflammation and airway remodeling, characteristic features of chronic asthma, if not treated could lead to permanent structural changes in the airways. Aldose reductase (AR), an aldo-sugar and lipid aldehyde metabolizing enzyme, mediates allergen-induced airway inflammation in mice, but its role in the airway remodeling is not known. In the present study, we have examined the role of AR on airway remodeling using ovalbumin (OVA)-induced chronic asthma mouse model and cultured human primary airway epithelial cells (SAECs) and mouse lung fibroblasts (mLFs).

Methods

Airway remodeling in chronic asthma model was established in mice sensitized and challenged twice a week with OVA for 6 weeks. AR inhibitor, fidarestat, was administered orally in drinking water after first challenge. Inflammatory cells infiltration in the lungs and goblet cell metaplasia, airway thickening, collagen deposition and airway hyper-responsiveness (AHR) in response to increasing doses of methacholine were assessed. The TGFβ1-induced epithelial-mesenchymal transition (EMT) in SAECs and changes in mLFs were examined to investigate AR-mediated molecular mechanism(s) of airway remodeling.

Results

In the OVA-exposed mice for 6 wks inflammatory cells infiltration, levels of inflammatory cytokines and chemokines, goblet cell metaplasia, collagen deposition and AHR were significantly decreased by treatment with AR inhibitor, fidarestat. Further, inhibition of AR prevented TGFβ1-induced altered expression of E-cadherin, Vimentin, Occludin, and MMP-2 in SAECs, and alpha-smooth muscle actin and fibronectin in mLFs. Further, in SAECs, AR inhibition prevented TGFβ1- induced activation of PI3K/AKT/GSK3β pathway but not the phosphorylation of Smad2/3.

Conclusion

Our results demonstrate that allergen-induced airway remodeling is mediated by AR and its inhibition blocks the progression of remodeling via inhibiting TGFβ1-induced Smad-independent and PI3K/AKT/GSK3β-dependent pathway.     

Tailoring of Localized Surface Plasmon Resonances of Core-Shell Au@Ag Nanorods by Changing the Thickness of Ag Shell

We report the synthesis and the characterization of core-shell Au@Ag nanorods through reduction by the wet chemical method. UV-visible absorption spectra of core-shell Au@Ag nanorods demonstrate the longitudinal mode of localized surface plasmon resonances (LSPRs) can be tailored from 724 to 786 nm by controlling the thickness of the silver shell, as is assessed by transmission electron microscope (TEM). Furthermore, the tunable and well-controlled LSPRs of core-shell Au@Ag nanorods are also investigated by numerical simulation using the finite difference time domain (FDTD) method, which strongly supports the experimental observations. The growth mechanism for core-shell Au@Ag nanorods is proposed, according to experimental observations and numerical calculations.     

Analysis of Mid-Infrared Surface Plasmon Modes in a Graphene-Based Cylindrical Hybrid Waveguide

A graphene-based cylindrical hybrid surface plasmon polariton waveguide, composed of a silicon nanowire core surrounded by a silica layer and then a graphene layer, is investigated using the finite-difference time-domain method. The analytical solutions and the numerical simulation show that an ultra-small mode area and a large propagation length can be achieved with this waveguide. Utilizing the perturbation theory of coupled mode, we demonstrate that the six lowest-order coupling modes originate from the coupling of the three lowest-order single-waveguide modes, and the m?=?1 order yy-coupling mode possesses the maximum coupling length and the minimum crosstalk. This waveguide can be used for photonic integrated circuits in the mid-infrared range.     

Magnetic-Based Fano Resonance by a Trimer with Y-shaped Gap

We introduce a Y-shaped gap into a silver disk to break the structure symmetry which can be looked as a loop-linked structure. Magnetic resonances are excited by incident light when incident electric field is parallel to the trimer plane. Fano resonance is generated by the coupling between bright electric mode and dark magnetic mode. These resonances can be adjusted by tuning the gap size, the radius of trimer, and the position of Y-shaped gap. The extinction cross section of the structure is calculated with the finite element method (FEM). The maximum figure of merit (FOM) is 37.8. Both the magnetic and electric field are greatly enhanced at the Fano dip and the magnetic resonance peak.     

Heat Treatment and β-Carotene Incorporation Effect in the Interaction of β-Lactoglobulin and Carboxymethylcellulose System

Encapsulation technologies using proteins or polysaccharides can be employed with the purpose of solubilizing and protecting carotenoids. However, information on the role of protein and polysaccharide interactions is still slightly limited. The aim of this work was to investigate the effect of β-carotene linked to protein β-lactoglobulin (BLG) in the interaction carboxymethylcellulose (CMC) using isothermal titration calorimetry (ITC). Firstly, BLG and CMC interaction was assessed by means of turbidity analysis. Based on the results of turbidity, the thermodynamic profile of BLG-CMC complexes at pH 4.0 was obtained using ITC analysis at 25 °C. Afterward, it was evaluated the effect of a thermal treatment applied to the BLG (68 °C for 50 min) in the interaction with CMC also using ITC and circular dichroism (CD). ITC and CD analysis showed that the heat treatment applied on BLG did not cause changes in molecular interactions. The binding isotherm of BLG-CMC complexes incorporated with β-carotene showed an increase in the molar ratio and a slight decrease in enthalpy of the system. Incorporation of β-carotene in the system did not significantly affect the BLG and CMC interaction, suggesting this system can be applied in food application as encapsulation.     

Flow Behavior of Native Corn and Potato Starch Granules in Aqueous Suspensions

The flow behavior of native corn and potato starch granule suspensions prepared in a concentrated sucrose solution has been investigated. Measurements were performed using a rotational rheometer with a concentric cylinder geometry. Starch suspensions were dilute to semi-concentrated (1 % to 25 % by volume). Shear and dynamic viscosity were measured by shear flow and dynamic oscillatory testing at 20, 50 and 80 °C. The starch suspensions exhibited essentially Newtonian behavior at all solid contents, although at higher solid volume fractions there was evidence of slight shear thickening. The relative viscosity of suspensions increased with increasing starch granule content, and the data conformed well to Maron-Pierce’s equation. An increase in maximum packing fraction and gravitational depletion of the starch granules with increasing temperature resulted in lower relative viscosities at higher temperatures. Also, the relative viscosities of potato starch granule suspensions with bigger, more oval and anisometric particles were lower than those of corn starch suspensions where granules were closer to sphericity but were angular in shape. Oscillatory shear testing results showed the presence of viscoelastic properties at intermediate solid volume fractions at low frequencies; in addition, the relative shear viscosity was higher than the relative dynamic viscosity, probably due to the formation of shear-induced structures during the shear flow test.     

Optical Response of Plasmonic Nanohole Arrays: Comparison of Square and Hexagonal Lattices

Nanohole arrays in metal films allow extraordinary optical transmission (EOT); the phenomenon is highly advantageous for biosensing applications. In this article, we theoretically investigate the performance of refractive index sensors, utilizing square and hexagonal arrays of nanoholes, that can monitor the spectral position of EOT signals. We present near- and far-field characteristics of the aperture arrays and investigate the influence of geometrical device parameters in detail. We numerically compare the refractive index sensitivities of the two lattice geometries and show that the hexagonal array supports larger figure-of-merit values due to its sharper EOT response. Furthermore, the presence of a thin dielectric film that covers the gold surface and mimics a biomolecular layer causes larger spectral shifts within the EOT resonance for the hexagonal array. We also investigate the dependence of the transmission responses on hole radius and demonstrate that hexagonal lattice is highly promising for applications demanding strong light transmission.     

Broad Tunable Nanoantenna Based on Graphene Log-Periodic Toothed Structure

A log-periodic toothed nanoantenna based on graphene is proposed, and its multi-resonance properties with respect to the variations of the chemical potential are investigated. The field enhancement and radar cross-section of the antenna for different chemical potentials are calculated, and the effect of the chemical potential on the resonance frequency is analyzed. In addition, the dependence of the resonance frequency on the substrate is also discussed. It is shown that large modulation of resonance intensity in log-periodic toothed nanoantenna can be achieved via turning the chemical potential of graphene. The tunability of the resonant frequencies of the antenna can be used to broad tuning of spectral features. The property of tunable multi-resonant field enhancement has great prospect in the field of graphene-based broadband nanoantenna, which can be applied in non-linear spectroscopy, optical sensor, and near-field optical microscopy.