Abstract Robust in vitro lung models are required for risk assessment to measure key events leading respiratory diseases. Primary normal human bronchial epithelial cells (NHBE) represent a good model but obtaining well-differentiated 3D cultures can be challenging. Here, we evaluated the ability expand primary NHBE different culture conditions while maintaining their characteristics such as ciliated and goblet cells, ion channel function. Differentiated were optimally obtained with...

Restoration of the epithelial barrier following acute lung injury is critical for recovery homeostasis. After injury, alveolar type II (ATII) cells spread and migrate to cover denuded surface and, eventually, proliferate differentiate into I cells. The chemokine CXCL12, also known as stromal cell-derived factor 1α, has well-recognized roles in organogenesis, hematopoiesis, immune responses through its binding receptor CXCR4. While CXCL12/CXCR4 signaling be important cell migration, role this...

Abstract Quercetin (QT) and Taxifolin (TF) are structurally similar plant polyphenols. Both have been reported to therapeutic potential as anti‐cancer drugs antioxidants. Mutagenic effects of QT TF were evaluated using Salmonella typhimurium TA102 Escherichia coli WP‐2 uvrA tester strains. Either in the presence or absence S9 mix, was mutagenic WP2 uvrA. However, mutagenicity significantly enhanced mix. Likewise, Iron (Fe2+) NADPH generating system (NGS) induced high mutations both ....

Alveolar type II (ATII) epithelial cells play a crucial role in the repair and remodeling of lung following injury. ATII have capability to proliferate differentiate into alveolar I (ATI) vivo an ATI-like phenotype vitro. While previous reports indicate that differentiation ATI is complex biological process, underlying mechanism responsible for not fully understood. To investigate factors involved this culture, we used PCR array identified several genes were either up- or downregulated (day...

Patients with severe acute lung injury are frequently administered high concentrations of oxygen (>50%) during mechanical ventilation. Long-term exposure to levels can cause in the absence ventilation, but combination two accelerates and increases injury. Hyperoxia causes cells through generation excessive reactive species. However, precise mechanisms that lead epithelial reasons for increased caused by ventilation not well understood. We hypothesized alveolar (AECs) may be more susceptible...

Both high tidal volume mechanical ventilation (HV) and hyperoxia (HO) have been implicated in ventilator-induced lung injury. However, patients with acute injury are often exposed to HO before the application of ventilation. The potential priming lungs for subsequent by exposure has not extensively studied. We provide evidence that (90%) 12 h followed HV (25 μl/g) combined 2 or 4 (HO-12h+HVHO-2h -4h) induced severe mice. Analysis homogenates showed was associated cleavage executioner...

Biomarkers of exposure (BoE) can help evaluate to combustion-related, tobacco-specific toxicants after smokers switch from cigarettes potentially less-harmful products like electronic nicotine delivery systems (ENDS). This paper reports data for one (Vuse Solo Original) three evaluated in a randomized, controlled, confinement study BoE switched ENDS. Subjects smoked their usual brand cigarette ad libitum two days, then were randomized ENDS 7-day use period, or smoking abstinence. Thirteen...

Abstract 4‐Aminobyphenyl (4‐Ab), benzidine (Bz), and Bz congeners were evaluated for their ability to induce genotoxicity through an oxidative mechanism. The mutagenicity of these compounds was tested in the presence absence Aroclor 1254‐induced rat S9 mix using Salmonella typhimurium tester strain TA102, which is sensitive agents producing reactive oxygen species (ROS). In S9, 4‐Ab, Bz, N ‐acetyl‐benzidine, 3,3′‐dimethoxybenzidine strongly mutagenic whereas, 3,3′,5,5′‐tetra‐methylbenzidine,...

Hyperoxia can lead to a myriad of deleterious effects in the lung including epithelial damage and diffuse inflammation. The specific mechanisms by which hyperoxia promotes these pathological changes are not completely understood. Activation ion channels has been proposed as one required for cell activation mediator secretion. two-pore-domain K + channel (K2P) Trek-1 recently described cells, but its function remains elusive. In this study we hypothesized that affects expression alveolar...

We previously reported the expression of two-pore-domain K channel TREK-1 in lung epithelial cells and proposed a role for this regulation alveolar cytokine secretion. In study, we focused on investigating vivo development hyperoxia-induced injury.Laboratory animal experiments.University research laboratory.Wild-type TREK-1-deficient mice.Mice were anesthetized exposed to 1) room air, no mechanical ventilation, 2) 95% hyperoxia 24 hours, 3) hours followed by ventilation 4 hours.Hyperoxia...

Cigarette smoking is known to disrupt the normal mucociliary function of lungs, whereas effect electronic nicotine delivery systems (ENDS) not completely understood. This study aimed compare effects acute exposure primary human bronchial epithelial (NHBE) 3D cultures at air-liquid interface combustible cigarette and ENDS preparations on function, including ion channel ciliary beat frequency (CBF), airway surface liquid (ASL) height. Differentiated NHBE were exposed whole smoke-conditioned...

Both prolonged exposure to hyperoxia and large tidal volume mechanical ventilation can each independently cause lung injury. However, the combined impact of these insults is poorly understood. We recently reported that preexposure for 12 h, followed by with volumes, induced significant injury epithelial cell apoptosis compared either stimulus alone (Makena et al. Am J Physiol Lung Cell Mol 299: L711-L719, 2010). The upstream mechanisms this have not been clearly elucidated. hypothesized in...

Radiation-induced damage to the retina triggers leukostasis, retinal endothelial cell (REC) death, and subsequent hypoxia. Resultant ischemia leads visual loss compensatory neovascularization (RNV). Using human RECs, we demonstrated that radiation induced leukocyte adhesion through mechanisms involving p38MAPK, p53, ICAM-1 activation. Additional phenotypic changes included p38MAPK-dependent tyrosine phosphorylation of focal scaffolding protein, paxillin (Tyr118). The quinic acid derivative...

Introduction of new tobacco products in the United States, including those that may be lower on risk continuum than traditional combustible cigarettes, requires premarket authorization by US Food and Drug Administration information potential impact consumer behaviors. Efficient recruitment data capture processes are needed to collect relevant a near-to-real-world environment.The aim this pilot study was develop test protocol for an actual use product. The product included commercially...

Both hyperoxia and mechanical ventilation can independently cause lung injury. In combination, these insults produce accelerated severe We recently reported that pre-exposure to for 12 hours, followed by with large tidal volumes, induced significant injury epithelial cell apoptosis compared either stimulus alone. also such are inhibited antioxidant treatment. this study, we hypothesized signal-regulating kinase-1 (ASK-1), a redox-sensitive, mitogen-activated protein kinase kinase, plays role...

Assessment of in vitro cytotoxicity is an important component tobacco product toxicological evaluations. However, current methods regulatory testing involve exposing monolayer cell cultures to various preparations aerosols from cigarettes or other emerging products such as electronic nicotine delivery systems (ENDS), which are not representative human exposure. In the present study, a whole aerosol (WA) system was used expose lung epithelial (2D and 3D) determine potential six Vuse Alto ENDS...

Heated tobacco products (HTPs) are non-combustible, inhaled that generate an aerosol with fewer and lower levels of toxicants, a potential to reduce risk relative cigarette smoking. Here, we assessed in vitro toxicological effects three menthol (glo neo neoCLICK, Smooth Menthol Fresh Menthol) one non-menthol (neo Tobacco) variants glo HTP, along market comparators for cigarettes HTPs. Limited chemical characterization the study revealed significantly acetaldehyde, acrolein, crotanaldehyde...

Electronic nicotine delivery systems (ENDS) have the potential to provide tobacco consumers while reducing exposure combustion-related toxicants. Here, we report changes in biomarkers of (BoE) and harm (BoPH) smokers who completely switched Vuse Vibe Ciro ENDS products, or smoking abstinence a randomized, controlled clinical study. Thirteen BoE (12 urinary one blood) that indicate harmful potentially toxicants (HPHCs) were evaluated at baseline on day 5. Urinary BoPH linked oxidative stress,...

Heated tobacco products (HTPs) are a class of non-combustible, inhaled with the potential to reduce harm associated cigarette smoking due reduced smoke toxicant exposure. Subjective and nicotine pharmacokinetics measures taken over course product use provide framework for abuse liability (AL) assessment as well information on adoption new product, which important aspects premarket authorization by US Food Drug Administration. This study aimed assess AL glo HTPs, operated in either Standard...

Modified risk tobacco products (MRTP) can reduce harm by decreasing exposure to combustion-related toxicants. In the absence of epidemiologic data, biomarkers potential (BoPH) are useful evaluate harm-reducing MRTPs. This study evaluated whether arachidonic acid (AA)-derived metabolites serve as short-term BoPH for predicting reduction in product-switching studies.We used 24-hour urine samples from participants a series studies which smokers switched combustible noncombustible [oral...