Cellular signalling pathways mediating the pathogenesis of chronic inflammatory respiratory diseases: an update

Respiratory disorders, especially non-communicable, chronic inflammatory diseases, are amongst the leading causes of mortality and morbidity worldwide. Respiratory diseases involve multiple pulmonary components, including airways and lungs that lead to their abnormal physiological functioning. Several signaling pathways have been reported to play an important role in the pathophysiology of respiratory diseases. These pathways, in addition, become the compounding factors contributing to the clinical outcomes in respiratory diseases. A range of signaling components such as Notch, Hedgehog, Wingless/Wnt, bone morphogenetic proteins, epidermal growth factor and fibroblast growth factor is primarily employed by these pathways in the eventual cascade of events. The different aberrations in such cell-signaling processes trigger the onset of respiratory diseases making the conventional therapeutic modalities ineffective. These challenges have prompted us to explore novel and effective approaches for the prevention and/or treatment of respiratory diseases. In this review, we have attempted to deliberate on the current literature describing the role of major cell signaling pathways in the pathogenesis of pulmonary diseases and discuss promising advances in the field of therapeutics that could lead to novel clinical therapies capable of preventing or reversing pulmonary vascular pathology in such patients

Estimation of the poly (ε-caprolactone) [PCL] and α-cyclodextrin [α-CD] stoichiometric ratios in their inclusion complexes [ICs], and evaluation of porosity and fiber alignment in PCL nanofibers containing these ICs

This paper describes the utilization of Proton-Nuclear Magnetic Resonance spectroscopy (1H NMR) to quantify the stoichiometric ratios between poly (ε-caprolactone) [PCL] and α-cyclodextrin (α-CD) present in their non-stoichiometric inclusion complexes [(n-s)-ICs]. This paper further describes the porosity and fiber alignment of PCL nanofibers nucleated by the [(n-s)-ICs] during electrospinning. 1H NMR indicated that the two non-stoichiometric inclusion complexes utilized in this study had differing stoichiometric ratios that were closely similar to those of the starting ratios used to make them. Studies on porosity and fiber alignments were conducted on the scanning electron microscope images using ImageJ. The data indicates that both fiber alignment as well as porosity values remain almost the same over all the samples. Thus we can conclude the improvement in mechanical properties was due only to the loading of the ICs, and their subsequent interaction with bulk unthreaded PCL

Buffers more than buffering agent: introducing a new class of stabilizers for the protein BSA

In this study, we have analyzed the influence of four biological buffers on the thermal stability of bovine serum albumin (BSA) using dynamic light scattering (DLS). The investigated buffers include 4-(2-hydroxyethyl) piperazine-1-ethanesulfonic acid (HEPES), 4-(2-hydroxyethyl)-1-piperazine-propanesulfonic acid (EPPS), 4-(2-hydroxyethyl) piperazine-1-ethanesulfonic acid sodium salt (HEPES-Na), and 4-morpholine-propanesulfonic acid sodium salt (MOPS-Na). These buffers behave as a potential stabilizer for the native structure of BSA against thermal denaturation. The stabilization tendency follows the order of MOPS-Na > HEPES-Na > HEPES >> EPPS. To obtain an insight into the role of hydration layers and peptide backbone in the stabilization of BSA by these buffers, we have also explored the phase transition of a thermoresponsive polymer, poly(N-isopropylacrylamide (PNIPAM)), a model compound for protein, in aqueous solutions of HEPES, EPPS, HEPES-Na, and MOPS-Na buffers at different concentrations. It was found that the lower critical solution temperatures (LCST) of PNIPAM in the aqueous buffer solutions substantially decrease with increase in buffer concentration. The mechanism of interactions between these buffers and protein BSA was probed by various techniques, including UV-visible, fluorescence, and FTIR. The results of this series of studies reveal that the interactions are mainly governed by the influence of the buffers on the hydration layers surrounding the protein. We have also explored the possible binding sites of BSA with these buffers using a molecular docking technique. Moreover, the activities of an industrially important enzyme alpha-chymotrypsin (alpha-CT) in 0.05 M, 0.5 M, and 1.0 M of HEPES, EPPS, HEPES-Na, and MOPS-Na buffer solutions were analyzed at pH = 8.0 and T = 25 degrees C. Interestingly, the activities of alpha-CT were found to be enhanced in the aqueous solutions of these investigated buffers. Based upon the Jones-Dole viscosity parameters, the kosmotropic or chaotropic behaviors of the investigated buffers at 25 degrees C have been examined

Treatment of Coffee Husk with Ammonium-Based Ionic Liquids: Lignin Extraction, Degradation, and Characterization

Four ammonium-based ionic liquids were synthesized for the selective extraction and degradation of lignin from coffee husk. The extracted lignin samples were characterized by Fourier transform infrared, gel permeation chromatography, gas chromatography–mass spectrometry, UV–vis, ¹H and ¹³C NMR, heteronuclear single-quantum coherence-NMR, thermogravimetric analysis, X-ray diffraction, and field emission scanning electron microscopy analyses. The analyzed results confirmed that these ionic liquids are able to effectively extract and decompose the lignin to smaller molecules from the biomass. Experimental results show that a significantly high yield, 71.2% of the original lignin, has been achieved. This processing method is an efficient, economical, and environmentally friendly green route for producing high-added-value lignin from wasted coffee husk

Poly(ε-caprolactone) Nanowebs Functionalized with α- and γ‑Cyclodextrins

The effects of alpha- and gamma-cyclodextrins (α- and γ-CDs) on the thermal and crystal nucleation behavior of electrospun poly­(ε-caprolactone) (PCL) nanofibers have been investigated. PCL/CD composite nanofibers were obtained for the first time by electrospinning the mixture from chloroform/<i>N,N</i>-dimethylformamide (60:40). Scanning electron microscopy analyses indicated that neat PCL nanofibers have an average diameter of 400 nm, which increases with the addition of CDs. The presence of CDs on or in the electrospun PCL fibers in the electrospun mats was investigated using Fourier transform infrared spectroscopy, thermogravimetric analysis, and wide-angle X-ray diffraction analysis. Differential scanning calorimetry showed that the PCL/CD composite fibers exhibit higher crystallization temperatures and sharper crystallization exotherms with increased CD loading, indicating the ability of CDs to nucleate PCL crystallization. Water contact angle (WCA) measurements indicate an inverse relationship between WCA and α- or γ-CD concentration up to 30% loading. Phenolphthalein absorption tests were performed to study the kinetics of their inclusion complex (IC) formation with CDs. Unexpectedly, γ-CD-functionalized nanowebs performed better than α-CD. This might be because at elevated loadings some α-CDs may have threaded over PCL chains and formed ICs, whereas γ-CD did not. With their encapsulation capabilities and their lowered hydrophobicity, PCL/CD composite fibers might have potential uses in medical applications, in particular as wound odor absorbants in dressings, because it is well known that CDs can form ICs with these odorants, thereby effectively removing them

Aliphatic Polyester Nanofibers Functionalized with Cyclodextrins and Cyclodextrin-Guest Inclusion Complexes

The fabrication of nanofibers by electrospinning has gained popularity in the past two decades; however, only in this decade, have polymeric nanofibers been functionalized using cyclodextrins (CDs) or their inclusion complexes (ICs). By combining electrospinning of polymers with free CDs, nanofibers can be fabricated that are capable of capturing small molecules, such as wound odors or environmental toxins in water and air. Likewise, combining polymers with cyclodextrin-inclusion complexes (CD-ICs), has shown promise in enhancing or controlling the delivery of small molecule guests, by minor tweaking in the technique utilized in fabricating these nanofibers, for example, by forming core–shell or multilayered structures and conventional electrospinning, for controlled and rapid delivery, respectively. In addition to small molecule delivery, the thermomechanical properties of the polymers can be significantly improved, as our group has shown recently, by adding non-stoichiometric inclusion complexes to the polymeric nanofibers. We recently reported and thoroughly characterized the fabrication of polypseudorotaxane (PpR) nanofibers without a polymeric carrier. These PpR nanofibers show unusual rheological and thermomechanical properties, even when the coverage of those polymer chains is relatively sparse (~3%). A key advantage of these PpR nanofibers is the presence of relatively stable hydroxyl groups on the outer surface of the nanofibers, which can subsequently be taken advantage of for bioconjugation, making them suitable for biomedical applications. Although the number of studies in this area is limited, initial results suggest significant potential for bone tissue engineering, and with additional bioconjugation in other areas of tissue engineering. In addition, the behaviors and uses of aliphatic polyester nanofibers functionalized with CDs and CD-ICs are briefly described and summarized. Based on these observations, we attempt to draw conclusions for each of these combinations, and the relationships that exist between their presence and the functional behaviors of their nanofibers

Application of Buffer-Based Ionic Liquid in the Separation of 1,4-Dioxane from Its Azeotropic Aqueous Solution

We have found that the ionic liquid (IL) [TMA]­[EPPS] could induce liquid–liquid phase splitting in the aqueous solution of 1,4-dioxane at ambient conditions. This IL is composed of <i>tetra</i>methylammonium (TMA) as a cation and a biological buffer, 4-(2-hydroxyethyl)-1-piperazinepropanesulfonic acid (EPPS), as an anion. The efficiency of this buffer-based IL for separating 1,4-dioxane from its aqueous solution has been evaluated on the basis of the liquid–liquid equilibrium (LLE) and solid–liquid–liquid equilibrium (SLLE) data of 1,4-dioane + water + [TMA]­[EPPS] at 298.15 K and under atmospheric pressure. The experimental LLE phase boundary data were correlated with an empirical equation and the effective excluded volume (EEV) model, respectively. The consistency of the LLE tie-line data was confirmed by using the Othmer–Tobias model. The binary interaction parameters of the NRTL model for each pair were obtained by correlating the experimental LLE and SLLE tie-line data. By using [TMA]­[EPPS] as an auxiliary agent, the maximum concentrations of 1,4-dioxane (97.8 wt %) in the organic-rich phase is greater than the azeotropic compositions (87.82 wt %) of the corresponding aqueous system. It clearly indicates that [TMA]­[EPPS] can be served as a high efficiency, noncorrosive, and biocompatible green agent for recovering high purity of 1,4-dioxane from its aqueous solution

Fabrication and Characterization of Poly(ε-caprolactone)/α-Cyclodextrin Pseudorotaxane Nanofibers

Multifunctional scaffolds comprising neat poly­(ε-caprolactone) (PCL) and α-cyclodextrin pseudorotaxanated in α-cyclodextrin form have been fabricated using a conventional electrospinning process. Thorough in-depth characterizations were performed on the pseudorotaxane nanofibers prepared from chloroform (CFM) and CFM/dimethylformamide (DMF) utilizing scanning electron microscopy (SEM), transmission electron microscopy (TEM), rheology, differential scanning calorimetry (DSC), thermogravimetric analyses (TGA), wide-angle X-ray diffraction (WAXD), and Instron tensile testing. The results indicate the nanofibers obtained from chloroform retain the rotaxanated structure; while those obtained from CFM/DMF had significantly dethreaded during electrospinning. As a consequence, the nanowebs obtained from CFM showed higher moduli and lower elongations at break compared to neat PCL nanowebs and PCL/α-CD nanowebs electrospun from CFM/DMF