Expression of SLC26A9 in Airways and Its Potential Role in Asthma

SLC26A9 is an epithelial anion transporter with a poorly defined function in airways. It is assumed to contribute to airway chloride secretion and airway surface hydration. However, immunohistochemistry showing precise localization of SLC26A9 in airways is missing. Some studies report localization near tight junctions, which is difficult to reconcile with a chloride secretory function of SLC26A9. We therefore performed immunocytochemistry of SLC26A9 in sections of human and porcine lungs. Obvious apical localization of SLC26A9 was detected in human and porcine superficial airway epithelia, whereas submucosal glands did not express SLC26A9. The anion transporter was located exclusively in ciliated epithelial cells. Highly differentiated BCi-NS1 human airway epithelial cells grown on permeable supports also expressed SLC26A9 in the apical membrane of ciliated epithelial cells. BCi-NS1 cells expressed the major Cl⁻ transporting proteins CFTR, TMEM16A and SLC26A9 in about equal proportions and produced short-circuit currents activated by increases in intracellular cAMP or Ca²⁺. Both CFTR and SLC26A9 contribute to basal chloride currents in non-stimulated BCi-NS1 airway epithelia, with CFTR being the dominating Cl⁻ conductance. In wtCFTR-expressing CFBE human airway epithelial cells, SLC26A9 was partially located in the plasma membrane, whereas CFBE cells expressing F508del-CFTR showed exclusive cytosolic localization of SLC26A9. Membrane localization of SLC26A9 and basal chloride currents were augmented by interleukin 13 in wild-type CFTR-expressing cells, but not in cells expressing the most common disease-causing mutant F508del-CFTR. The data suggest an upregulation of SLC26A9-dependent chloride secretion in asthma, but not in the presence of F508del-CFTR.     

A New Model and Quality of Unfrozen and Frozen Cooked Rice Dried in a Microwave Vibro-Fluidized Bed Dryer

This study aimed to develop a suitable drying model for microwave vibro-fluidized bed drying in a single-mode applicator (MVFB-SMA drying) of cooked rice with and without prefreezing treatment and to investigate the effects of prefreezing treatment and drying temperature (110–185°C) on quality of dried cooked rice. During the process of drying cooked rice from 60 to 10% (wet basis), results indicated that drying rate increased, whereas drying time decreased with prefreezing treatment and increased drying temperature. The drying rate and drying time of unfrozen and frozen cooked rice ranged from 0.196 to 0.497 g water/g dry matter/min and 0.228 to 0.554 g water/g dry matter/min; and from 7 to 2.5 min and 5.5 to 2 min, respectively. A new model was proposed in this study (MR = exp(?k t ⁿ ) + bt + c) to compare with 11 commonly used drying models. The new model describes the MVFB-SMA drying data most satisfactorily. The values of effective diffusivity were between 1.70 × 10^?7 and 5.72 × 10^?7 m²/s for the unfrozen sample and between 1.99 × 10^?7 and 5.86 × 10^?7 m²/s for the frozen sample. Their activation energy values were 23.66 and 21.19 kJ/mol, respectively. Prefreezing treatment provided a whiter product with a less uniform porous structure and higher bulk density. Slower ability to rehydrate was also observed for the frozen cooked rice dried at 160 and 185°C. An increase in drying temperature resulted in changes in whiteness, microstructure, bulk density, and rehydration capability. No prefreezing treatment and drying at 160°C seemed to be the optimal process condition for cooked rice, ensuring whiteness, a porous structure, low bulk density, and high rehydration capability.     

Airway Delivery of Hydrogel-Encapsulated Niclosamide for the Treatment of Inflammatory Airway Disease

Repurposing of the anthelminthic drug niclosamide was proposed as an effective treatment for inflammatory airway diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease. Niclosamide may also be effective for the treatment of viral respiratory infections, such as SARS-CoV-2, respiratory syncytial virus, and influenza. While systemic application of niclosamide may lead to unwanted side effects, local administration via aerosol may circumvent these problems, particularly when the drug is encapsulated into small polyethylene glycol (PEG) hydrospheres. In the present study, we examined whether PEG-encapsulated niclosamide inhibits the production of mucus and affects the pro-inflammatory mediator CLCA1 in mouse airways in vivo, while effects on mucociliary clearance were assessed in excised mouse tracheas. The potential of encapsulated niclosamide to inhibit TMEM16A whole-cell Cl⁻ currents and intracellular Ca²⁺ signalling was assessed in airway epithelial cells in vitro. We achieved encapsulation of niclosamide in PEG-microspheres and PEG-nanospheres (Niclo-spheres). When applied to asthmatic mice via intratracheal instillation, Niclo-spheres strongly attenuated overproduction of mucus, inhibited secretion of the major proinflammatory mediator CLCA1, and improved mucociliary clearance in tracheas ex vivo. These effects were comparable for niclosamide encapsulated in PEG-nanospheres and PEG-microspheres. Niclo-spheres inhibited the Ca²⁺ activated Cl⁻ channel TMEM16A and attenuated mucus production in CFBE and Calu-3 human airway epithelial cells. Both inhibitory effects were explained by a pronounced inhibition of intracellular Ca²⁺ signals. The data indicate that poorly dissolvable compounds such as niclosamide can be encapsulated in PEG-microspheres/nanospheres and deposited locally on the airway epithelium as encapsulated drugs, which may be advantageous over systemic application.     

Single-step synthesis of MWCNT/ZnO nanocomposite using co-chemical vapor deposition method

Single-step synthesis of MWCNT and ZnO nanocomposite was conducted by co-chemical vapor deposition method. Electron microscopic analysis revealed that the fabricated nanostructures consisted of MWCNTs with a diameter of 60-70 nm which were coated with ZnO nanoparticles with an average size of 20-30 nm. The growth of ZnO nanoparticles took place after the formation of MWCNTs. EDS and XRD analyses could confirm the high crystallinity of ZnO deposited on the MWCNT surface. In comparison with pristine MWCNTs and ZnO nanoparticles, the UV absorption of MWCNT/ZnO nanocomposite was changed through modification with ZnO nanoparticles.     

Investigating flow patterns in a channel with complex obstacles using the lattice Boltzmann method

In this work, mesoscopic modeling via a computational lattice Boltzmann method (LBM) is used to investigate the flow pattern phenomena and the physical properties of the flow field around one and two square obstacles inside a two-dimensional channel with a fixed blockage ratio, β=1/4, centered inside a 2D channel, for a range of Reynolds numbers (Re) from 1 to 300. The simulation results show that flow patterns can initially exhibit laminar flow at low Re and then make a transition to periodic, unsteady, and, finally, turbulent flow as the Re get higher. Streamlines and velocity profiles and a vortex shedding pattern are observed. The Strouhal numbers are calculated to characterize the shedding frequency and flow dynamics. The effect of the layouts or configurations of the obstacles are also investigated, and the possible connection between the mixing process and the appropriate design of a chemical mixing system is discussed.     

Micronization of Dihydroartemisinin by Rapid Expansion of Supercritical Solutions

The purpose of this study was to prepare fine particles of antimalarial drug dihydroartemisinin (DHA) by rapid expansion of supercritical solutions (RESS) using carbon dioxide as supercritical fluid. The mechanical grinding by jet mill and additional vibration rod mill also was performed as a comparative method. In the RESS process, drug particles were prepared by varying processing conditions, including extraction condition, pre-expansion condition, nozzle diameter, nozzle temperature, and collecting distance. Particle size and morphology and physicochemical characteristics of the drug particles were investigated. The RESS process could produce the smaller drug particles (about 1–2 μm) when compared to mechanical grinding method (about 7 μm). All RESS processing parameters had an effect on size and morphology of drug particles. The particle size of drug was related to the solubility of drug in supercritical CO₂ at each processing condition. The fine particles of DHA (about 1 μm) with narrow size distribution could be obtained at extraction pressure of 18 MPa and extraction temperature of 32°C, which was closed to the critical temperature of supercritical CO₂ whereas broad size distribution was obtained at extraction temperature of 60°C. Powder X-ray diffraction study indicated that the RESS-processed particles were in crystalline form. The results revealed that RESS process is applicable for micronization of DHA.     

Formation, physical stability and in vitro antimalarial activity of dihydroartemisinin nanosuspensions obtained by co-grinding method

The purpose of this study was to investigate the formation of drug nanoparticles from binary and ternary mixtures, consisting of dihydroartemisinin (DHA), a poorly water-soluble antimalarial drug, with water-soluble polymer and/or surfactant. Binary mixtures of drug/polyvinyl pyrrolidone K30 (PVP K30), binary mixtures of drug/sodium deoxycholate (NaDC), and ternary mixtures of drug/PVP K30/NaDC were prepared at different weight ratios and then ground by vibrating rod mill to obtain ground mixtures. Nanosuspension was successfully formed after dispersing ternary ground mixtures or DHA/NaDC ground mixtures in water. The ternary ground mixtures did not give superior nanosuspension in terms of particle size reduction and recovery of drug nanoparticles, but they provided more physically stable nanosuspensions than DHA/NaDC ground mixtures. The size of drug nanoparticles was decreased with increasing grinding time and lowering amount of PVP K30 and NaDC. About 95% of drug nanoparticles were found in the nanosuspension from ternary ground mixtures. Zeta potential measurement suggested that stable nanosuspension was attributable to adsorption of NaDC and PVP K30 onto surface of drug particles. Atomic force microscopy and transmission electron microscopy with selected area diffraction indicated that DHA in nanosuspension was existed as nanocrystals. The obtained nanosuspensions had higher in vitro antimalarial acitivity against Plasmodium falciparum than microsuspensions. The results suggest that co-grinding of DHA with PVP K30 and NaDC seems to be a promising method to prepare DHA nanosuspension.     

Peptides from the Intestinal Tract of Breast Milk-Fed Infants Have Antimicrobial and Bifidogenic Activity

For bioactive milk peptides to be relevant to infant health, they must be released by gastrointestinal proteolysis and resist further proteolysis until they reach their site of activity. The intestinal tract is the likeliest site for most bioactivities, but it is currently unknown whether bioactive milk peptides are present therein. The purpose of the present study was to identify antimicrobial and bifidogenic peptides in the infant intestinal tract. Milk peptides were extracted from infant intestinal samples, and the activities of the bulk peptide extracts were determined by measuring growth of Escherichia coli, Staphylococcus aureus, and Bifidobacterium longum spp. infantis after incubation with serial dilutions. The peptide profiles of active and inactive samples were determined by peptidomics analysis and compared to identify candidate peptides for bioactivity testing. We extracted peptides from 29 intestinal samples collected from 16 infants. Five samples had antimicrobial activity against S. aureus and six samples had bifidogenic activity for B. infantis. We narrowed down a list of 6645 milk peptides to 11 candidate peptides for synthesis, of which 6 fully inhibited E. coli and S. aureus growth at concentrations of 2500 and 3000 µg/mL. This study provides evidence for the potential bioactivity of milk peptides in the infant intestinal tract.