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Record W2522875240

Regulatory role of micro RNA in severe asthma

2015· article· en· W2522875240 on OpenAlexaff
Jamila Chakir

Bibliographic record

VenueBiological Systems Open Access · 2015
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer-related molecular mechanisms research
Canadian institutionsUniversité Laval
Fundersnot available
KeywordsAsthmaGene knockdownmicroRNAPathogenesisImmunologyRespiratory epitheliumMedicineEpitheliumInflammationCancer researchBiologyGenePathologyGenetics
DOInot available

Abstract

fetched live from OpenAlex

A asthma is a chronic inflammatory disease characterized by an airway hyper-responsiveness and a deregulated inflammation in response to allergens. Available treatments are mainly symptoms-driven and do not interfere with the natural history of the diseases. Severe asthma constitutes a challenging problem for the healthcare system. Its heterogeneity complicates the management of the disease. There is a significant need to understand the pathogenesis of severe asthma. Bronchial epithelium is considered a key player in coordinating airway wall remodeling. While in mild asthma, the epithelium is damaged and fails to proliferate and to repair in severe asthma the epithelium was reported to be highly proliferative and thicker. This may be due to different regulatory mechanisms. We studied microRNAs profile and evaluated their role in regulating proliferation of bronchial epithelial cells obtained from severe asthmatic subjects in comparison to cells obtained from mild asthmatics and healthy controls. We found that in mild asthma epithelial cells produce high amount of TGFβ1 and express high level of TGFβ-RI and phosphorylated-Smad3 indicating that TGFβ1signalling is up-regulated. In severe asthma, this pathway was down-regulated. Thus, in epithelial cells from severe asthmatics compared to mild asthma and controls, miR19a, a member of the miR-17~92 cluster is up-regulated and increases proliferation. Knockdown of miR-19a in epithelial cells reduces significantly their proliferation through targeting TGF-β downstream signaling. Our study uncovers a new regulatory pathway involving miR-19a that is critical to the severe phenotype of asthma and indicates that down-regulating miR-19a expression could be explored as a potential new therapy to modulate the epithelium repair in asthma.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.067
GPT teacher head0.365
Teacher spread0.298 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2015
Admission routes1
Has abstractyes

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