E-cigarette aerosols of propylene glycol impair BK channel activity and parameters of mucociliary function.

Propylene glycol (PG) is a common delivery vehicle for nicotine and flavorings in e-cigarette (e-cig) liquids and is largely considered safe for ingestion. However, little is known about its effects as an e-cig aerosol on the airway. Here, we investigated whether pure PG e-cig aerosols in realistic daily amounts impact parameters of mucociliary function and airway inflammation in a large animal model (sheep) in vivo and primary human bronchial epithelial cells (HBECs) in vitro.

Nebulized Menthol Impairs Mucociliary Clearance via TRPM8 and MUC5AC/MUC5B in Primary Airway Epithelial Cells.

Flavorings enhance the palatability of e-cigarettes (e-cigs), with menthol remaining a popular choice among e-cig users. Menthol flavor remains one of the only flavors approved by the United States FDA for use in commercially available, pod-based e-cigs. However, the safety of inhaled menthol at the high concentrations used in e-cigs remains unclear.

Vegetable glycerin e-cigarette aerosols cause airway inflammation and ion channel dysfunction.

Vegetable glycerin (VG) and propylene glycol (PG) serve as delivery vehicles for nicotine and flavorings in most e-cigarette (e-cig) liquids. Here, we investigated whether VG e-cig aerosols, in the absence of nicotine and flavors, impact parameters of mucociliary function in human volunteers, a large animal model (sheep), and air-liquid interface (ALI) cultures of primary human bronchial epithelial cells (HBECs). We found that VG-containing (VG or PG/VG), but not sole PG-containing, e-cig aerosols reduced the activity of nasal cystic fibrosis transmembrane conductance regulator (CFTR) in human volunteers who vaped for seven days.

Persistence of airway inflammation in smokers who switch to electronic cigarettes.

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Losartan ameliorates TGF-β1-induced CFTR dysfunction and improves correction by cystic fibrosis modulator therapies.

Highly effective modulator therapies dramatically improve the prognosis for those with cystic fibrosis (CF). The triple combination of elexacaftor, tezacaftor, and ivacaftor (ETI) benefits many, but not all, of those with the most common F508del mutation in the CF transmembrane conductance regulator (CFTR). Here, we showed that poor sweat chloride concentration responses and lung function improvements upon initiation of ETI were associated with elevated levels of active TGF-β1 in the upper airway.

Losartan reduces cigarette smoke-induced airway inflammation and mucus hypersecretion.

The aim was to determine whether losartan reduces cigarette smoke (CS)-induced airway inflammation and mucus hypersecretion in an model and a small clinical trial. Primary human bronchial epithelial cells (HBECs) were differentiated at the air-liquid interface (ALI) and exposed to CS. Expression of transforming growth factor (TGF)-β1 and the mucin MUC5AC, and expression or activity of matrix metalloproteinase (MMP)-9 were measured after CS exposure.

Hyperglycaemia in cystic fibrosis adversely affects BK channel function critical for mucus clearance.

Large-conductance, Ca-activated, voltage-dependent K (BK) channel function is critical for adequate airway hydration and mucociliary function. In airway epithelia, BK function is regulated by its γ-subunit, leucine-rich repeat-containing protein 26 (LRRC26). Since patients with cystic fibrosis (CF)-related diabetes mellitus (CFRD) have worse lung function outcomes, this study determined the effects of hyperglycaemia on BK function in CF bronchial epithelial (CFBE) cells and evaluated the correlation between glycaemic excursions and mRNA expression of in the upper airways of CF and CFRD patients.

The Effects of the Anti-aging Protein Klotho on Mucociliary Clearance.

α-klotho (KL) is an anti-aging protein and has been shown to exert anti-inflammatory and anti-oxidative effects in the lung and pulmonary diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis. The current study investigated the direct effect of KL on the bronchial epithelium in regards to mucociliary clearance parameters. Primary human bronchial and murine tracheal epithelial cells, cultured, and differentiated at the air liquid interface (ALI), were treated with recombinant KL or infected with a lentiviral vector expressing KL.

Losartan Rescues Inflammation-related Mucociliary Dysfunction in Relevant Models of Cystic Fibrosis.

Despite therapeutic progress in treating cystic fibrosis (CF) airway disease, airway inflammation with associated mucociliary dysfunction remains largely unaddressed. Inflammation reduces the activity of apically expressed large-conductance Ca-activated and voltage-dependent K (BK) channels, critical for mucociliary function in the absence of CFTR (CF transmembrane conductance regulator). To test losartan as an antiinflammatory therapy in CF using CF human bronchial epithelial cells and an ovine model of CF-like airway disease.

Electronic Cigarette Vapor with Nicotine Causes Airway Mucociliary Dysfunction Preferentially via TRPA1 Receptors.

Electronic cigarette (e-cig) use has been widely adopted under the perception of safety. However, possibly adverse effects of e-cig vapor in never-smokers are not well understood. To test the effects of nicotine-containing e-cig vapors on airway mucociliary function in differentiated human bronchial epithelial cells isolated from never-smokers and in the airways of a novel, ovine large animal model.

Role of Smad3 and p38 Signalling in Cigarette Smoke-induced CFTR and BK dysfunction in Primary Human Bronchial Airway Epithelial Cells.

Mucociliary clearance (MCC) is a major airway host defence system that is impaired in patients with smoking-associated chronic bronchitis. This dysfunction is partially related to a decrease of airway surface liquid (ASL) volume that is in part regulated by apically expressed cystic fibrosis transmembrane conductance regulator (CFTR) and large-conductance, Ca-activated, and voltage dependent K (BK) channels. Here, data from human bronchial epithelial cells (HBEC) confirm that cigarette smoke not only downregulates CFTR activity but also inhibits BK channel function, thereby causing ASL depletion.

Synthetic Architecture of MgO/C Nanocomposite from Hierarchical-Structured Coordination Polymer toward Enhanced CO Capture.

Highly efficient, durable, and earth-abundant solid sorbents are of paramount importance for practical carbon capture, storage, and utilization. Here, we report a novel and facile two-step strategy to synthesize a group of hierarchically structured porous MgO/C nanocomposites using flowerlike Mg-containing coordination polymer as a precursor. The new nanocomposites exhibit superb CO capture performance with sorption capacity up to 30.

In situ studies of materials for high temperature CO capture and storage.

Carbon capture and storage (CCS) offers a possible solution to curb the CO emissions from stationary sources in the coming decades, considering the delays in shifting energy generation to carbon neutral sources such as wind, solar and biomass. The most mature technology for post-combustion capture uses a liquid sorbent, amine scrubbing. However, with the existing technology, a large amount of heat is required for the regeneration of the liquid sorbent, which introduces a substantial energy penalty.

Transcription factor Sp1 inhibition, memory, and cytokines in a mouse model of Alzheimer's disease.

Transcription factors are involved to varying extents in the health and survival of neurons in the brain and a better understanding of their roles with respect to the pathogenesis of Alzheimer's disease (AD) could lead to the development of additional treatment strategies. Sp1 is a transcription factor that responds to inflammatory signals occurring in the AD brain. It is known to regulate genes with demonstrated importance in AD, and we have previously found it upregulated in the AD brain and in brains of transgenic AD model mice.

Roflumilast partially reverses smoke-induced mucociliary dysfunction.

Background: Phosphodiesterases (PDEs) break down cAMP, thereby regulating intracellular cAMP concentrations and diffusion. Since PDE4 predominates in airway epithelial cells, PDE4 inhibitors can stimulate Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) by increasing cAMP. Tobacco smoking and COPD are associated with decreased CFTR function and impaired mucociliary clearance (MCC).

Airway Surface Dehydration by Transforming Growth Factor β (TGF-β) in Cystic Fibrosis Is Due to Decreased Function of a Voltage-dependent Potassium Channel and Can Be Rescued by the Drug Pirfenidone.

Transforming growth factor β1 (TGF-β1) is not only elevated in airways of cystic fibrosis (CF) patients, whose airways are characterized by abnormal ion transport and mucociliary clearance, but TGF-β1 is also associated with worse clinical outcomes. Effective mucociliary clearance depends on adequate airway hydration, governed by ion transport. Apically expressed, large-conductance, Ca(2+)- and voltage-dependent K(+) (BK) channels play an important role in this process.

Transforming growth factor-β1 and cigarette smoke inhibit the ability of β2-agonists to enhance epithelial permeability.

Chronic bronchitis, caused by cigarette smoke exposure, is characterized by mucus hypersecretion and reduced mucociliary clearance (MCC). Effective MCC depends, in part, on adequate airway surface liquid. Cystic fibrosis transmembrane conductance regulator (CFTR) provides the necessary osmotic gradient for serosal to mucosal fluid transport through its ability to both secrete Cl(-) and regulate paracellular permeability, but CFTR activity is attenuated in chronic bronchitis and in smokers.

Phycobilisome-Deficient Strains of Synechocystis sp. PCC 6803 Have Reduced Size and Require Carbon-Limiting Conditions to Exhibit Enhanced Productivity.

Reducing excessive light harvesting in photosynthetic organisms may increase biomass yields by limiting photoinhibition and increasing light penetration in dense cultures. The cyanobacterium Synechocystis sp. PCC 6803 harvests light via the phycobilisome, which consists of an allophycocyanin core and six radiating rods, each with three phycocyanin (PC) discs.

Adapting Data Processing To Compare Model and Experiment Accurately: A Discrete Element Model and Magnetic Resonance Measurements of a 3D Cylindrical Fluidized Bed.

Discrete element modeling is being used increasingly to simulate flow in fluidized beds. These models require complex measurement techniques to provide validation for the approximations inherent in the model. This paper introduces the idea of modeling the experiment to ensure that the validation is accurate.

IFN-γ-mediated reduction of large-conductance, Ca2+-activated, voltage-dependent K+ (BK) channel activity in airway epithelial cells leads to mucociliary dysfunction.

Effective mucociliary clearance (MCC) depends in part on adequate airway surface liquid (ASL) volume to maintain an appropriate periciliary fluid height that allows normal ciliary activity. Apically expressed large-conductance, Ca(2+)-activated, and voltage-dependent K(+) (BK) channels provide an electrochemical gradient for Cl(-) secretion and thus play an important role for adequate airway hydration. Here we show that IFN-γ decreases ATP-mediated apical BK activation in normal human airway epithelial cells cultured at the air-liquid interface.

The purification of crude glycerol derived from biodiesel manufacture and its use as a substrate by Rhodopseudomonas palustris to produce hydrogen.

Crude glycerol (CG) from biodiesel production is often contaminated with several compounds, including saponified fatty acids (SFAs). Photofermentative growth of Rhodopseudomonas palustris on glycerol leads to hydrogen production; however, R. palustris is inhibited by SFAs.

Thylakoid terminal oxidases are essential for the cyanobacterium Synechocystis sp. PCC 6803 to survive rapidly changing light intensities.

Cyanobacteria perform photosynthesis and respiration in the thylakoid membrane, suggesting that the two processes are interlinked. However, the role of the respiratory electron transfer chain under natural environmental conditions has not been established. Through targeted gene disruption, mutants of Synechocystis sp.

Photofermentation of crude glycerol from biodiesel using Rhodopseudomonas palustris: comparison with organic acids and the identification of inhibitory compounds.

The growth of the biodiesel industry, and its concurrent production of glycerol, has lowered the price of glycerol 20-fold. While many options for using this glycerol have been proposed, the size of the waste stream means that generation of fuels is likely to be the only viable route. One such fuel is hydrogen, production of which can be achieved biologically.

Treatment of Phaeodactylum tricornutum cells with papain facilitates lipid extraction.

Triacylglycerols (TAGs) from microalgae have the potential to be used for biodiesel, but several technical and economic hurdles have to be overcome. A major challenge is efficient extraction of intracellular TAGs from algae. Here we investigate the use of enzymes to deconstruct algal cell walls/membranes.

Modeling the pathobiology of repetitive traumatic brain injury in immortalized neuronal cell lines.

Repetitive mild traumatic brain injury (mTBI) represents a major public health problem. Many individuals who suffer repetitive mTBIs suffer from Post-Concussion Syndrome, a constellation of neuropsychiatric symptoms that includes depression, anxiety, and problems with memory and other cognitive processes. Significantly, Post-Concussion Syndrome is resistant to existing therapeutic strategies.