37 research outputs found
Aldose Reductase Inhibition Prevents Metaplasia of Airway Epithelial Cells
BACKGROUND: Goblet cell metaplasia that causes mucus hypersecretion and obstruction in the airway lumen could be life threatening in asthma and chronic obstructive pulmonary disease patients. Inflammatory cytokines such as IL-13 mediate the transformation of airway ciliary epithelial cells to mucin-secreting goblet cells in acute as well as chronic airway inflammatory diseases. However, no effective and specific pharmacologic treatment is currently available. Here, we investigated the mechanisms by which aldose reductase (AR) regulates the mucus cell metaplasia in vitro and in vivo. METHODOLOGY/FINDINGS: Metaplasia in primary human small airway epithelial cells (SAEC) was induced by a Th2 cytokine, IL-13, without or with AR inhibitor, fidarestat. After 48 h of incubation with IL-13 a large number of SAEC were transformed into goblet cells as determined by periodic acid-schiff (PAS)-staining and immunohistochemistry using antibodies against Mucin5AC. Further, IL-13 significantly increased the expression of Mucin5AC at mRNA and protein levels. These changes were significantly prevented by treatment of the SAEC with AR inhibitor. AR inhibition also decreased IL-13-induced expression of Muc5AC, Muc5B, and SPDEF, and phosphorylation of JAK-1, ERK1/2 and STAT-6. In a mouse model of ragweed pollen extract (RWE)-induced allergic asthma treatment with fidarestat prevented the expression of IL-13, phosphorylation of STAT-6 and transformation of epithelial cells to goblet cells in the lung. Additionally, while the AR-null mice were resistant, wild-type mice showed goblet cell metaplasia after challenge with RWE. CONCLUSIONS: The results show that exposure of SAEC to IL-13 caused goblet cell metaplasia, which was significantly prevented by AR inhibition. Administration of fidarestat to mice prevented RWE-induced goblet cell metaplasia and AR null mice were largely resistant to allergen induced changes in the lung. Thus our results indicate that AR inhibitors such as fidarestat could be developed as therapeutic agents to prevent goblet cell metaplasia in asthma and related pathologies
Design and Implementation of a Novel Behavioral Sciences Course for First Year Medical Students
Protein-Ligand Blind Docking Using QuickVina-W With Inter-Process Spatio-Temporal Integration
The oxidative stress response of the yeastCandida intermedia to copper, zinc, and selenium exposure
Smart integration of sensors, computer vision and knowledge representation for intelligent monitoring and verbal human-computer interaction
Contrasting Fire Regimes in a Seasonally Dry Tropical Forest and a Savanna Ecosystem in the Western Ghats, India
High-dose melphalan with autologous hematopoietic stem cell transplantation for acute myeloid leukemia: results of a retrospective analysis of the Italian Pediatric Group for Bone Marrow Transplantation
Treatment and long-term results in children with acute myeloid leukaemia treated according to the AIEOP AML protocols
High density silvopasture systems for quality forage production and carbon sequestration in humid tropics of Southern India
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CEERS Key Paper. IV. A Triality in the Nature of HST-dark Galaxies
Abstract
The new capabilities that JWST offers in the near- and mid-infrared (IR) are used to investigate in unprecedented detail the nature of optical/near-IR-faint, mid-IR-bright sources, with HST-dark galaxies among them. We gather JWST data from the CEERS survey in the Extended Groth Strip, jointly with HST data, and analyze spatially resolved optical-to-mid-IR spectral energy distributions to estimate photometric redshifts in two dimensions and stellar population properties on a pixel-by-pixel basis for red galaxies detected by NIRCam. We select 138 galaxies with F150W − F356W > 1.5 mag and F356W < 27.5 mag. The nature of these sources is threefold: (1) 71% are dusty star-forming galaxies (SFGs) at 2 < z < 6 with
9
<
log
M
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/
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<
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and a variety of specific SFRs (<1 to >100 Gyr−1); (2) 18% are quiescent/dormant (i.e., subject to reignition/rejuvenation) galaxies (QGs) at 3 < z < 5, with
log
M
⋆
/
M
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and poststarburst mass-weighted ages (0.5–1.0 Gyr); and (3) 11% are strong young starbursts with indications of high equivalent width emission lines (typically, [O iii]+Hβ) at 6 < z < 7 (XELG-z6) and
log
M
⋆
/
M
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∼
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. The sample is dominated by disk-like galaxies with remarkable compactness for XELG-z6 (effective radii smaller than 0.4 kpc). Large attenuations in SFGs, 2 < A(V) < 5 mag, are found within 1.5 times the effective radius, approximately 2 kpc, while QGs present A(V) ∼ 0.2 mag. Our SED-fitting technique reproduces the expected dust emission luminosities of IR-bright and submillimeter galaxies. This study implies high levels of star formation activity between z ∼ 20 and z ∼ 10, where virtually 100% of our galaxies had already formed 108
M
⊙, 60% had assembled 109
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⊙, and 10% up to 1010
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⊙ (in situ or ex situ).</jats:p