miR-636: A Newly-Identified Actor for the Regulation of Pulmonary Inflammation in Cystic Fibrosis

Cystic fibrosis (CF) results from deficient CF transmembrane conductance regulator (CFTR) protein activity leading to defective epithelial ion transport. Pulmonary degradation due to excessive inflammation is the main cause of morbidity and mortality in CF patients. By analysing miRNAs (small RNAseq) in human primary air-liquid interface cell cultures, we measured the overexpression of miR-636 in CF patients compared to non-CF controls. We validated these results in explant biopsies and determined that the mechanism underlying miR-636 overexpression is linked to inflammation. To identify specific targets, we used bioinformatics analysis to predict whether miR-636 targets the 3′-UTR mRNA regions of IL1R1 and RANK (two pro-inflammatory cytokine receptors), IKBKB (a major protein in the NF-κB pathway), and FAM13A (a modifier gene of CF lung phenotype implicated in epithelial remodelling). Using bronchial epithelial cells from CF patients to conduct a functional analysis, we showed a direct interaction between miR-636 and IL1R1, RANK, and IKBKB, but not with FAM13A. These interactions led to a decrease in IL1R1 and IKKβ protein expression levels, while we observed an increase in RANK protein expression levels following the overexpression of miR-636. Moreover, NF-κB activity and IL-8 and IL-6 secretions decreased following the transfection of miR-636 mimics in CF cells. Similar but opposite effects were found after transfection with an antagomiR-636 in the s...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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CONCLUSION: The analysis of the presence of 5T polymporphism in CBAVD patients may add information when predicting the outcome of assisted reproductive techniques. PMID: 31797807 [PubMed - in process]
Source: Archivos Espanoles de Urologia - Category: Urology & Nephrology Tags: Arch Esp Urol Source Type: research
(Burness) Amidst rising hopes for using CRISPR gene editing tools to repair deadly mutations linked to conditions like cystic fibrosis and sickle cell disease, a new study in the Nature journal Communications Biology describes a new innovation that could accelerate this work by rapidly revealing unintended and potentially harmful changes introduced by a gene editing process.
Source: EurekAlert! - Biology - Category: Biology Source Type: news
Condition:   Nonalcoholic Fatty Liver Disease Interventions:   Behavioral: Guided Grocery Shopping (GGS);   Other: Diet Provision Group Sponsors:   Emory University;   Center for Cystic Fibrosis and Airways Disease Research Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Condition:   Cystic Fibrosis Interventions:   Other: Autogenic drainage;   Device: SIMEOX + Autogenic drainage Sponsor:   Cliniques universitaires Saint-Luc- Université Catholique de Louvain Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Condition:   Nonalcoholic Fatty Liver Disease Interventions:   Behavioral: Guided Grocery Shopping (GGS);   Other: Diet Provision Group Sponsors:   Emory University;   Center for Cystic Fibrosis and Airways Disease Research Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Cystic Fibrosis pulmonary disease is characterized by chronic airway infections and concomitant non-resolving inflammation that usually leads to respiratory failure within the fourth decade of life. The disease results from patients bearing two mutant copies of the cystic fibrosis transmembrane conductance regulator (CFTR), a channel that transports chloride and bicarbonate [1]. Over 2000 different mutations in CFTR have been identified, and these mutations are associated with varying severity of disease based on how much residual CFTR activity remains.
Source: Journal of Cystic Fibrosis - Category: Respiratory Medicine Authors: Tags: Original Article Source Type: research
AbstractThe contribution of T-cells after lung transplant (LTx) remains controversial with no current consensus of their role concerning chronic lung allograft dysfunction. Using flow cytometry to assess T-cell subsets of bronchoalveolar lavage fluid (BALF) in 16 cystic fibrosis (CF) LTx recipients, we identified a decline in CD4+ T-cell frequency and an increase in CD8+ T-cell frequency in patients who developed severe bronchiolitis obliterans syndrome (BOS) (N = 10) when comparing baseline (6 months post-LTx) and follow-up (most recent bronchoscopy—clinical or surveillance per protocol). Comparin...
Source: Lung - Category: Respiratory Medicine Source Type: research
CONCLUSIONS: We found no evidence that adding hip core decompression to physical therapy achieves clinical improvement in people with sickle cell disease with avascular necrosis of bone compared to physical therapy alone. However, we highlight that our conclusion is based on one trial with high attrition rates. Further randomized controlled trials are necessary to evaluate the role of hip-core depression for this clinical condition. Endpoints should focus on participants' subjective experience (e.g. quality of life and pain) as well as more objective 'time-to-event' measures (e.g. mortality, survival, hip longevity). The a...
Source: Cochrane Database of Systematic Reviews - Category: General Medicine Authors: Tags: Cochrane Database Syst Rev Source Type: research
ConclusionsThe synbiotic had no significant effect on pulmonary and anthropometric outcomes in children with CF. Further studies are necessary to confirm these findings.
Source: European Journal of Integrative Medicine - Category: Complementary Medicine Source Type: research
Abstract Airway surface dehydration is a pathological feature of cystic fibrosis (CF) lung disease. CF is caused by mutations in the CF transmembrane conductance regulator (CFTR), a cyclic AMP-regulated Cl- channel controlled in part by the adenosine A2B receptor. An alternative, CFTR-independent mechanism of fluid secretion is regulated by ATP, via the P2Y2 receptor (P2Y2R) that activates Ca2+-regulated Cl- channels (CaCC/TMEM16) and inhibits Na+ absorption. However, due to rapid ATP hydrolysis, steady-state ATP levels in CF airway surface liquid (ASL) are inadequate to maintain P2Y2R-mediated fluid secretion. Th...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research
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