The role of non-coding RNAs in vascular damage in hypertension and CKD
Bibliographic record
Abstract
Hypertension and chronic kidney disease (CKD) are two of the most prevalent global health concerns that account for millions of deaths per year.They are both associated with vascular damage that is characterized by vascular remodeling and stiffening, as well as endothelial dysfunction, which contribute to further development of the disease and lead to end organ damage.MicroRNAs (miRNAs) are important non-coding RNA regulators of gene expression that cause translational repression and transcript degradation upon binding to their target mRNAs.miRNAs have been demonstrated to be associated with hypertension and CKD, and play a critical role in vascular cell development and function.However, their role in vascular damage is still poorly studied.We hypothesized that vascular and circulating miRNAs are dysregulated in hypertension and CKD; the dysregulation of vascular miRNAs is a key driving force of pathological gene expression changes that contribute to vascular damage; key dysregulated vascular miRNAs are potential therapeutic targets and key dysregulated circulating miRNAs are potential biomarkers for vascular damage in hypertension and CKD.The thesis contains 3 studies testing our hypotheses.viii miR-382-5p, et a augmenté Ehf dans les AM, et a retardé l'élévation de la PA et ré duit les dommages vasculaires chez les souris infusées avec l'Ang II pendant 14 jours.Dans la deuxiè me é tude, nous avons profilé les miARN comme plus haut dans les petites artè res de biopsies sous-cutané es de la fesse de sujets non hypertendus, hypertendus ou atteints d'IRC.En combinant les donné es de cette é tude avec celles de la premiè re é tude, nous avons trouvé un miARN commun, miR-145-3p, qui é tait diminué dans les souris infusé es avec l'Ang II pendant 7 jours et les patients avec IRC.Cependant, il reste à pré ciser si miR-145-3p agit sur les dommages vasculaires dans le modè le d'hypertension induit par l'Ang II et dans l'IRC.Dans la troisiè me é tude, nous avons profilé les miARN circulant dans le plasma de la cohorte de sujets de l'étude précédente.Nous avons identifié 4 miARN exprimé s diffé rentiellement, let-7g-5p, miR-26a-5p, miR-191-5p et let-7b-5p.let-7g-5p é tait corré lé avec le taux de filtration glomé rulaire estimé .Nous avons é galement trouvé une corré lation entre let-7g-5p et les gè nes exprimé s de faç on diffé rentielle dans les petites artè res de patients avec IRC.En ré sumé , miR-431-5p et sa cible Ehf pourraient agir comme des ré gulateurs maî tres des dommages vasculaires dans l'hypertension.miR-431-5p a le potentiel de servir comme cible thé rapeutique pour contrer les dommages vasculaires et l'hypertension.miR-145-3p pourrait jouer un rôle dans le dé veloppement des dommages vasculaires induits par l'Ang II et l'IRC.Let-7g-5p a un potentiel clinique pour servir comme biomarqueur des dommages vasculaires dans l'IRC.xv
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".