The circulating methylome in childhood-onset inflammatory bowel disease.

The genetic contribution to inflammatory bowel disease (IBD) encompassing both Crohn's disease (CD) and ulcerative colitis (UC), accounts for around 20% of disease variance, highlighting the need to characterise environmental and epigenetic influences. Recently considerable progress has been made in characterising the adult methylome, in epigenome-wide association studies. We report detailed analysis of the circulating methylome in 86 patients with childhood-onset CD,UC and 30 controls using the Illumina Infinium Human MethylationEPIC platform.

Patient-derived organoid biobank identifies epigenetic dysregulation of intestinal epithelial MHC-I as a novel mechanism in severe Crohn's Disease.

Objective: Epigenetic mechanisms, including DNA methylation (DNAm), have been proposed to play a key role in Crohn's disease (CD) pathogenesis. However, the specific cell types and pathways affected as well as their potential impact on disease phenotype and outcome remain unknown. We set out to investigate the role of intestinal epithelial DNAm in CD pathogenesis.

Uncovering the gastrointestinal passage, intestinal epithelial cellular uptake, and AGO2 loading of milk miRNAs in neonates using xenomiRs as tracers.

Background: Human breast milk has a high microRNA (miRNA) content. It remains unknown whether and how milk miRNAs might affect intestinal gene regulation and homeostasis of the developing microbiome after initiating enteral nutrition. However, this requires that relevant milk miRNA amounts survive the gastrointestinal (GI) passage, are taken up by cells, and become available to the RNA interference machinery.

Making Research Flourish Through ESPGHAN: A Position Paper From the ESPGHAN Special Interest Group for Basic and Translational Research.

Recent research breakthroughs have emerged from applied basic research throughout all scientific areas, including adult and paediatric gastroenterology, hepatology and nutrition (PGHAN). The research landscape within the European Society of Paediatric Gastroenterology and Nutrition (ESPGHAN) is also inevitably changing from clinical research to studies involving applied laboratory research. This position paper aims to depict the current status quo of basic science and translational research within ESPGHAN, and to delineate how the society could invest in research in the present and future time.

Improving prediction of disease outcome for inflammatory bowel disease: progress through systems medicine.

Inflammatory bowel diseases (IBDs) are lifelong conditions causing relapsing inflammation of the intestine. In the absence of a cure, clinical management of IBDs is extremely challenging since they present with a wide range of phenotypes and disease behaviors. Hence, there is an urgent need for markers that could guide physicians in making the right choice of the rapidly growing treatment options toward a personalized care that could improve the overall outcome.

The mystery behind the nostrils - technical clues for successful nasal epithelial cell cultivation.

Objectives: Research involving the nose reveals important information regarding the morphology and physiology of the epithelium and its molecular response to agents. The role of nasal epithelial cells and other cell subsets within the nasal epithelium play an interesting translational split between experimental and clinical research studying respiratory disorders or pathogen reactions. With an additional technical manuscript including a detailed description of important technical aspects, tips, tricks, and nuances for a successful culturing of primary, human nasal epithelial cells (NAEPCs), we here aim to improve the process of communication between experimentalists and physicians, supporting the purpose of a fruitful work for future translational projects.

From Submerged Cultures to 3D Cell Culture Models: Evolution of Nasal Epithelial Cells in Asthma Research and Virus Infection.

Understanding the response to viral infection in the context of respiratory diseases is of significant importance. Recently, there has been more focus on the role of the nasal epithelium in disease modeling. Here, we provide an overview of different submerged, organotypic 3D and spheroid cell culture models of nasal epithelial cells, which were used to study asthma and allergy with a special focus on virus infection.

Impact of an In-House Pediatric Surgery Unit and Human Milk Centered Enteral Nutrition on Necrotizing Enterocolitis.

The importance for mortality and morbidity of an in-house pediatric surgery unit for premature infants with necrotizing enterocolitis (NEC) remains undefined. Data on 389 consecutive very low birth weight infants with a birth weight <1250 g admitted between 2009 and 2014 was retrospectively analyzed in two almost identical neonatal intensive care units. Epidemiological data (n=172 and n=217, respectively) were comparable.

The Prevalence of GNAS Deficiency-Related Diseases in a Large Cohort of Patients Characterized by the EuroPHP Network.

Context: The term pseudohypoparathyroidism (PHP) was coined to describe the clinical condition resulting from end-organ resistance to parathormone (rPTH), caused by genetic and/or epigenetic alterations within or upstream of GNAS. Although knowledge about PHP is growing, there are few data on the prevalence of underlying molecular defects.

Objective: The purpose of our study was to ascertain the relative prevalence of PHP-associated molecular defects.

Screening of PRKAR1A and PDE4D in a Large Italian Series of Patients Clinically Diagnosed With Albright Hereditary Osteodystrophy and/or Pseudohypoparathyroidism.

The cyclic adenosine monophosphate (cAMP) intracellular signaling pathway mediates the physiological effects of several hormones and neurotransmitters, acting by the activation of G-protein coupled receptors (GPCRs) and several downstream intracellular effectors, including the heterotrimeric stimulatory G-protein (Gs), the cAMP-dependent protein kinase A (PKA), and cAMP-specific phosphodiesterases (PDEs). Defective G-protein-mediated signaling has been associated with an increasing number of disorders, including Albright hereditary osteodistrophy (AHO) and pseudohypoparathyroidism (PHP), a heterogeneous group of rare genetic metabolic disorders resulting from molecular defects at the GNAS locus. Moreover, mutations in PRKAR1A and PDE4D genes have been recently detected in patients with acrodysostosis (ACRDYS), showing a skeletal and endocrinological phenotype partially overlapping with AHO/PHP.