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Purpose: Sulfur mustard, nitrogen mustard (NM), and 2-chloroethyl ethyl sulfide all cause corneal injury with epithelial-stromal separation, differing only by degree. Injury can resolve in a few weeks or develop into chronic corneal problems. These vesicants induce microbullae at the epithelial-stromal junction, which is partially caused by cleavage of transmembranous hemidesmosomal collagen XVII, a component anchoring the epithelium to the stroma. ADAM17 is an enzyme involved in wound healing and is able to cleave collagen XVII. The activity of ADAM17 was inhibited in vesicant-exposed corneas by four different hydroxamates, to evaluate their therapeutic potential when applied 2 hours after exposure, thereby allowing ADAM17 to perform its early steps in wound healing.
Methods: Rabbit corneal organ cultures exposed to NM for 2 hours were washed, then incubated at 37°C for 22 hours, with or without one of the four hydroxamates (dose range, 0.3-100 nmol in 20 μL, applied four times). Corneas were analyzed by light and immunofluorescence microscopy, and ADAM17 activity assays.
Results: Nitrogen mustard-induced corneal injury showed significant activation of ADAM17 levels accompanying epithelial-stromal detachment. Corneas treated with hydroxamates starting 2 hours post exposure showed a dose-dependent ADAM17 activity inhibition up to concentrations of 3 nmol. Of the four hydroxamates, NDH4417 (N-octyl-N-hydroxy-2-[4-hydroxy-3-methoxyphenyl] acetamide) was most effective for inhibiting ADAM17 and retaining epithelial-stromal attachment.
Conclusions: Mustard exposure leads to corneal epithelial sloughing caused, in part, by the activation of ADAM17 at the epithelial-stromal junction. Select hydroxamate compounds applied 2 hours after NM exposure mitigated epithelial-stromal separation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829087 | PMC |
http://dx.doi.org/10.1167/iovs.15-17269 | DOI Listing |
Heliyon
December 2024
Department of Clinical Laboratory Medicine, Wenzhou Central Hospital, Dingli Clinical School of Wenzhou Medical University, Wenzhou, 325000, China.
Background: The relationship between tumour necrosis factor (TNF) levels and disease progression is well-established. However, the impact of changes in the level of TNF hydrolase (A-disintegrin and metalloenzyme 17; ADAM17) in HIV patients remains to be fully elucidated.
Methods: Between March 1 and December 31, 2017, data were collected from 64 HIV-positive individuals in Wenzhou.
Front Immunol
December 2024
Goethe University Frankfurt, University Hospital, Department of Trauma Surgery and Orthopedics, Frankfurt, Germany.
Background: Extracellular vesicles (EVs), a heterogeneous group of cell-derived, membrane-enclosed vesicles bearing cell-specific epitopes, have been demonstrated to play a crucial role in neuronal-glial communication and the orchestration of neuroinflammatory processes. However, the existing evidence regarding their function as biomarkers and their role in the pathobiology of traumatic spinal cord injuries (tSCI), particularly in humans, is scarce.
Objective: The primary goal of this study was to investigate whether a distinct pattern of EV surface epitopes detected in the plasma of individuals suffering from spinal cord injury is indicative of tSCI.
J Clin Invest
December 2024
Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
Understanding cell fate regulation in the liver is necessary to advance cell therapies for hepatic disease. Liver progenitor cells (LPC) contribute to tissue regeneration after severe hepatic injury yet signals instructing progenitor cell dynamics and fate are largely unknown. The Tissue Inhibitor of Metalloproteinases, TIMP1 and TIMP3 control the sheddases ADAM10 and ADAM17, key for NOTCH activation.
View Article and Find Full Text PDFCells
December 2024
Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA.
Human immunodeficiency virus type-1 (HIV-1) associated comorbidities account for the majority of poor health outcomes in people living with HIV (PLWH) in the era of antiretroviral therapy. Lung-related comorbidities such as chronic obstructive pulmonary disease (COPD) and bacterial pneumonia are primarily responsible for increased morbidity and mortality in PLWH, even when compensated for smoking. Smokers and COPD patients demonstrate cilia shortening, attenuated ciliary beat frequency (CBF), dysfunctional ciliated cells along with goblet cell hyperplasia, and mucus hypersecretion.
View Article and Find Full Text PDFInt J Pharm
December 2024
Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address:
Background: In this study, we investigate the impact of a multi-targeted therapeutic approach that includes camptothecin (CPT), a potent chemotherapeutic topoisomerase inhibitor; metformin (Met), a metabolic modulator with emerging anti-tumor effects; and GW280264X, an inhibitor of ADAM 10/ADAM 17 enzymes, which are associated with tumor invasion and immune response. The study aims to assess the combined effects of these agents in enhancing CD8 T cell-mediated anti-tumor immunity and suppressing cancer cell growth in triple-negative breast cancer (TNBC) models, both in vitro and in vivo.
Methods: Cell viability was performed on the 4 T1 human TNBC cell line.
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