Objectives/hypothesis: Evidence indicates that decreased mucociliary clearance (MCC) is a major contributing feature to chronic rhinosinusitis. Tobacco-smoke exposure is thought to inhibit transepithelial Cl(-) secretion, a major determinant of airway surface liquid hydration and MCC. The objective of the current study was to evaluate the effects of acrolein exposure (a prominent tobacco smoke toxin) on vectorial Cl(-) transport through the major apical anion channel cystic fibrosis transmembrane conductance regulator (CFTR) in sinonasal epithelium.
Study Design: In vitro investigation.
Methods: Primary murine nasal septal epithelia (MNSE; wild-type and transgenic CFTR(-/-)) cultures were exposed to acrolein in Ussing chambers and the effects on Cl(-) secretion investigated using pharmacologic manipulation. Cellular cyclic adenosine monophosphate (cAMP) signaling and cytotoxicity were also investigated.
Results: Acrolein stimulated Cl(-) secretion (ΔI(SC) - change in short-circuit current in μA/cm(2)) at concentrations similar to smoker's airways (100 μM, 15.8 ± 2.2 vs. 2.4 ± 0.8 [control]; P < .0001), suppressed forskolin-stimulated C- transport at 300 μM (13.3 ± 1.2 vs. 19.9 ± 1.0; P < .01), and completely abolished all transport at 500 μM (-1.1 ± 1.6). Stimulated Cl(-) secretion was solely reliant upon the presence of CFTR (confirmed in transgenic CFTR(-/-) MNSE), but independent of cAMP signaling. Inhibition at higher concentrations was not secondary to cellular cytotoxicity.
Conclusions: The present study demonstrates that acrolein has complex but pronounced interaction with the major apical Cl(-) transport mechanism that uses CFTR. Further investigations are required to determine acrolein's impact as a tobacco smoke constituent on mucociliary transport.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548450 | PMC |
| http://dx.doi.org/10.1002/lary.23278 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Verification of the Impact of Changes in the Severity Classification of Proteinuria on the Prognosis of Hypertensive Patients Following the Initiation of Esaxerenone.
Circ Rep
January 2025
Department of Diabetes/Endocrinology and Metabolism, Minoh City Hospital Osaka Japan.
Background: The urinary albumin-to-creatinine ratio (UACR) or urinary protein-to-creatinine ratio (UPCR) has been reported as predictors of cardiovascular and renal events. We aimed to evaluate the impact of changes in proteinuria severity on the prognosis of hypertensive patients post-esaxerenone initiation.
Methods And Results: Hypertensive patients who commenced esaxerenone (n=164) were classified into 3 groups according to baseline UACR or UPCR, based on the modified proteinuria severity classification: A1 (normal; n=35); A2 (microalbuminuria/mild proteinuria; n=49); and A3 (macroalbuminuria/severe proteinuria; n=80).
Life stage impact on the human skin ecosystem: lipids and the microbial community.
NPJ Biofilms Microbiomes
January 2025
A*STAR Skin Research Labs (A*SRL), Agency for Science, Technology, and Research (A*STAR) & Skin Research Institute of Singapore (SRIS), Singapore, Republic of Singapore.
Sebaceous free fatty acids are metabolized by multiple skin microbes into bioactive lipid mediators termed oxylipins. This study investigated correlations between skin oxylipins and microbes on the superficial skin of pre-pubescent children (N = 36) and adults (N = 100), including pre- (N = 25) and post-menopausal females (N = 25). Lipidomics and metagenomics revealed that Malassezia restricta positively correlated with the oxylipin 9,10-DiHOME on adult skin and negatively correlated with its precursor, 9,10-EpOME, on pre-pubescent skin.
View Article and Find Full Text PDFGut dysbiosis was inevitable, but tolerance was not: temporal responses of the murine microbiota that maintain its capacity for butyrate production correlate with sustained antinociception to chronic morphine.
Gut Microbes
December 2025
Department of Molecular, Cellular, & Biomedical Sciences, University of New Hampshire, Durham, NH, USA.
The therapeutic benefits of opioids are compromised by the development of analgesic tolerance, which necessitates higher dosing for pain management thereby increasing the liability for drug dependence and addiction. Rodent models indicate opposing roles of the gut microbiota in tolerance: morphine-induced gut dysbiosis exacerbates tolerance, whereas probiotics ameliorate tolerance. Not all individuals develop tolerance, which could be influenced by differences in microbiota, and yet no study design has capitalized upon this natural variation.
View Article and Find Full Text PDFFrontiers in laccase nanozymes-enabled colorimetric sensing: A review.
Anal Chim Acta
February 2025
Nanobiophotonics Department, Leibniz Institute of Photonic Technology (Leibniz-IPHT), Albert-Einstein-Strasse 9, 07745, Jena, Germany. Electronic address:
In recent years, nanozyme-based analytics have become popular. Among these, laccase nanozyme-based colorimetric sensors have emerged as simple and rapid colorimetric detection methods for various analytes, effectively addressing natural enzymes' stability and high-cost limitations. Laccase nanozymes are nanomaterials that exhibit inherent laccase enzyme-like activity.
View Article and Find Full Text PDFExpert opinion on Centiloid thresholds suitable for initiating anti-amyloid therapy. Summary of discussion at the 2024 spring Alzheimer's Association Research Roundtable.
J Prev Alzheimers Dis
January 2025
Memory & Aging Center, Departments of Neurology, Radiology & Biomedical Imaging, University of California San Francisco, San Francisco, California, USA.
A 24-30 Centiloid (CL) threshold was collectively considered by a group of global dementia experts as a practical and implementable cut-off for anti-amyloid therapy intervention, in Alzheimer's disease patients who have been diagnosed at the mild cognitive impairment or mild dementia stage of their disease. Though additional validation is needed, knowledge of this threshold would be valuable to those involved in diagnosing and treating patients in the new AD care pathways, as well as entry into clinical trials. Therapy monitoring to determine future treatment response and assess amyloid clearance can be accomplished with amyloid PET with some technical details still to be elucidated.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!