Objective: The objectives of this study were to characterize the endotypes of different chronic rhinosinusitis without nasal polyps (CRSsNP) samples, to investigate the effects of certain anti-inflammatory drugs on these endotypes, and to investigate the effect of the same drugs on recently identified CRSsNP marker proteins.
Patients And Methods: Initially, ethmoid tissues (ETs) from CRSsNP patients (n=12) were dissected into sections and incubated with the addition of mometasone, verapamil, cenicriviroc, and dupilumab. Cell culture media were collected after 24 hours, and the contents of the secreted proteins interferon-gamma (IFN-γ), interleukin (IL)-5, IL-17A, macrophage inflammatory protein-1 beta (MIP-1β), resistin and platelet (P)-selectin were measured using enzyme-linked immunosorbent assay (ELISA). The endotypes were characterized using the unstimulated samples. The fold changes of protein secretion caused by the analyzed substances were calculated. For each protein, the samples of the distinct endotypes were compared with the remaining samples.
Results: Both single and mixed endotypes were identified within the CRSsNP samples, whereas none of the typical endotype-defining cytokines were elevated in a significant portion of the samples. All of the incubated medicaments greatly reduced the tissue secretions of IFN-γ and IL-5 in type 1 CRS while causing a lower secretion of IL-17A in all endotypes compared to the remaining samples. Among the analyzed CRSsNP marker proteins, the distinct endotypes revealed different reactions to the drugs. Dupilumab induced more effects among the examined cytokines than the marker proteins but did not stand out from the other substances overall.
Conclusions: Medications used to treat CRS may have different effects on distinct CRS endotypes.
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http://dx.doi.org/10.26355/eurrev_202410_36872 | DOI Listing |
Genome Med
January 2025
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA.
Background: Large-scale pharmacogenomic resources, such as the Connectivity Map (CMap), have greatly assisted computational drug discovery. However, despite their widespread use, CMap-based methods have thus far been agnostic to the biological activity of drugs as well as to the genomic effects of drugs in multiple disease contexts. Here, we present a network-based statistical approach, Pathopticon, that uses CMap to build cell type-specific gene-drug perturbation networks and integrates these networks with cheminformatic data and diverse disease phenotypes to prioritize drugs in a cell type-dependent manner.
View Article and Find Full Text PDFJ Am Acad Dermatol
January 2025
Department of Dermatology, University of Maryland School of Medicine, Baltimore, MD; Maryland Itch Center, University of Maryland School of Medicine, Baltimore, MD. Electronic address:
Arthritis Rheumatol
January 2025
Department of Immunology and inflammation, Imperial College London, UK.
Background: Takayasu arteritis (TAK) and giant cell arteritis (GCA), the most common forms of large-vessel vasculitis (LVV), can result in serious morbidity. Understanding the molecular basis of LVV should aid in developing better biomarkers and treatments.
Methods: Plasma proteomic profiling of 184 proteins was performed in two cohorts.
Br J Anaesth
December 2024
Translational Medicine and Therapeutics, William Harvey Research Institute, Queen Mary University of London, London, UK. Electronic address:
Background: Hypertension therapy in older adults is often suboptimal, in part because of inadequate suppression of the renin-angiotensin-aldosterone system (RAAS). We hypothesised that distinct endotypes of RAAS activation before noncardiac surgery are associated with increased risk of myocardial injury.
Methods: This was a prespecified exploratory analysis of a multicentre randomised controlled trial (ISRCTN17251494) which randomised patients ≥60 yr old undergoing elective noncardiac surgery to either continue or stop RAAS inhibitors (determined by pharmacokinetic profiles).
Am J Respir Cell Mol Biol
December 2024
Stanford University, Institute for Immunity, Transplantation and Infection, Stanford, California, United States;
Asthma is a heterogeneous disease with variable presentation and characteristics. There is a critical need to identify underlying molecular endotypes of asthma. We performed the largest transcriptomic analysis of 808 bronchial epithelial cell (BEC) samples across 11 independent cohorts, including 3 cohorts from the Severe Asthma Research Program (SARP).
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