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New England Journal of Medicine, Volume 388, Issue 21, Page 1992-1999, May 2023.

‘Legge è necessaria, così colmeremo il gap con altri Paesi Ue’

‘Legge è necessaria, così colmeremo il gap con altri Paesi Ue’

Consulti medici gratuiti in venti piazze italiane

In piazze e studi iniziativa di Fondazione Andi, visite gratuite

Integrazione dati MMG su Rapporto Agenas personale sanitario, Silvestro Scotti (Fimmg): «Dati coerenti con la nostra denuncia sulla desertificazione della medicina territoriale. Ora si proceda ad un deciso cambio di passo»

New England Journal of Medicine, Volume 388, Issue 17, Page 1609-1615, April 2023.

Objective
The contribution of vitamin D (VD) deficiency to the pathogenesis of allergic diseases remains elusive. We aimed to define the impact of VD on oesophageal allergic inflammation.

Design
We assessed the genomic distribution and function of VD receptor (VDR) and STAT6 using histology, molecular imaging, motif discovery and metagenomic analysis. We examined the role of VD supplementation in oesophageal epithelial cells, in a preclinical model of IL-13-induced oesophageal allergic inflammation and in human subjects with eosinophilic oesophagitis (EoE).

Results
VDR response elements were enriched in oesophageal epithelium, suggesting enhanced VDR binding to functional gene enhancer and promoter regions. Metagenomic analysis showed that VD supplementation reversed dysregulation of up to 70% of the transcriptome and epigenetic modifications (H3K27Ac) induced by IL-13 in VD-deficient cells, including genes encoding the transcription factors HIF1A and SMAD3, endopeptidases (SERPINB3) and epithelial-mesenchymal transition mediators (TGFBR1, TIAM1, SRC, ROBO1, CDH1). Molecular imaging and chromatin immunoprecipitation showed VDR and STAT6 colocalisation within the regulatory regions of the affected genes, suggesting that VDR and STAT6 interactome governs epithelial tissue responses to IL-13 signalling. Indeed, VD supplementation reversed IL-13-induced epithelial hyperproliferation, reduced dilated intercellular spaces and barrier permeability, and improved differentiation marker expression (filaggrin, involucrin). In a preclinical model of IL-13-mediated oesophageal allergic inflammation and in human EoE, VD levels inversely associated with severity of oesophageal eosinophilia and epithelial histopathology.

Conclusions
Collectively, these findings identify VD as a natural IL-13 antagonist with capacity to regulate the oesophageal epithelial barrier functions, providing a novel therapeutic entry point for type 2 immunity-related diseases.

Marzo mese del sonno, Sognid’oro lancia progetto con Aims

Dopo 6 settimane di discesa dei contagi. Decessi -18,4%, ricoveri +4%

A Bologna. Impiantato a paziente nuovo stimolatore midollare

La gestione in remoto dopo chirurgia robotica consente di ridurre l’ospedalizzazione a due giornate, riducendo le liste di attesa. Il nuovo protocollo, messo a punto e validato dall’Istituto clinico Humanitas, è pubblicato su Cancer

Aice ottimista per il 2023