Perioperative adjuvant therapy with short course of dupilumab with ESS for recurrent CRSwNP.

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with a high rate of disease recurrence following endoscopic sinus surgery (ESS). Type 2 disease is associated with a higher incidence of recurrence and is believed to impact disease resolution via interference with epithelial healing and pathogen immunity. We wished to verify if perioperative control of Type 2 inflammation with an anti-IL4/IL13 targeting monoclonal antibody and during the resolution period following surgery leads to better control of the disease long term.

Utilization of Transcriptomic Profiling to Identify Molecular Markers Predicting Successful Recovery Following Endoscopic Sinus Surgery for Chronic Rhinosinusitis.

Objectives: Successful recovery from chronic rhinosinusitis (CRS) following endoscopic sinus surgery (ESS) can be characterized by minimal presence of symptoms and absence of disease on endoscopy. However, molecular markers of surgical success remain to be characterized. These could allow for better tailoring of perioperative therapy.

Chromatin opening ability of pioneer factor Pax7 depends on unique isoform and C-terminal domain.

Pioneer factors are transcription factors (TFs) that have the unique ability to recognise their target DNA sequences within closed chromatin. Whereas their interactions with cognate DNA is similar to other TFs, their ability to interact with chromatin remains poorly understood. Having previously defined the modalities of DNA interactions for the pioneer factor Pax7, we have now used natural isoforms of this pioneer as well as deletion and replacement mutants to investigate the Pax7 structural requirements for chromatin interaction and opening.

Response to intranasal probiotic supplementation in refractory CRS is associated with modulation of non-type 2 inflammation and epithelial regeneration.

Justification: We have previously documented that in individuals with chronic rhinosinusitis (CRS) refractory to surgery, intranasal application of live , a probiotic bacterium, improves sinus-specific symptoms, SNOT-22, and mucosal aspect on endoscopy, accompanied by a reduction in sinus pathogens and an increase in protective bacteria. The present work explores the molecular mechanisms underpinning these observations using transcriptomics of the sinus mucosa.

Method: Epithelial brushings collected prospectively as a sub-study of the clinical trial were used to probe epithelial responses to microbiome supplementation using a hypothesis-free bioinformatic analysis of gene expression analysis.

Pax7 pioneer factor action requires both paired and homeo DNA binding domains.

The pioneer transcription factor Pax7 contains two DNA binding domains (DBD), a paired and a homeo domain. Previous work on Pax7 and the related Pax3 showed that each DBD binds a cognate DNA sequence, thus defining two targets of binding and possibly modalities of action. Genomic targets of Pax7 pioneer action leading to chromatin opening are enriched for composite DNA target sites containing juxtaposed sites for both paired and homeo domains.

Pax factors in transcription and epigenetic remodelling.

The nine Pax transcription factors that constitute the mammalian family of paired domain (PD) factors play key roles in many developmental processes. As DNA binding transcription factors, they exhibit tremendous variability and complexity in their DNA recognition patterns. This is ascribed to the presence of multiple DNA binding structural domains, namely helix-turn-helix (HTH) domains.