The protective effect of fenretinide against allergic asthma
Bibliographic record
Abstract
Objective/purposeFenretinide [N-4-hydroxyphenyl, 4HPR] is a syntheticretinoid derived from vitamin A with pro-apoptotic andanti-inflammatory properties. Studies have shown thatat high concentrations fenretinide is an effective anti-neoplastic agent, regulating cell growth and differentia-tion. We have recently demonstrated that fenretinide, atdoses 5-10× lower than for cancer treatment, has pro-tective effect against bacterial infection[1] and osteo-porosis[2] in Cftr-knockout mice. The effect offenretinide as a potential treatment for allergic asthmainduced inflammation has not been evaluated in asth-matics. The goal of this study was to determine if, bynormalizing inflammatory mediators, fenretinide wouldbe able to alleviate the symptoms associated with aller-gic asthma.MethodsHyperresponsive to methacholine, mice of A/J strainwere sensitized weekly using ovalbumin (OVA) forthree consecutive weeks, then age-matched and sepa-rated into two study groups and two control groups.For a period of 4 weeks, the study groups were orallytreated with fenretinide while the controls were treatedwith the drug vehicle. During the last week of treat-ment, the control and study groups were split into twoadditional groups and underwent allergen challengesfor three consecutive days, with either an OVA solu-tion or PBS. Forty-eight hours after the third challenge,resistance of the respiratory system of the mice inresponse to methacholine was measured using a Buxcoplethysmograph. Total IgE in plasma was measured byELISA. Lung histopathology was observed using H&Eand PAS stains.FindingsVehicle treated OVA challenged mice exhibited highvalues of airway resistance, plasma IgE concentration,and immune cell infiltration into the airways comparedto PBS challenged animals. Interestingly, fenretinidetreated OVA challenged mice had a statistically lowerrespiratory resistance. In addition, fenretinide treatmentabrogated the recruitment of eosinophils to the regionsurrounding the blood vessels and airways. Similarly,after drug treatment a decrease in goblet cell hyperplasiawas also observed through histopathology. However, nodifference was observed in the level of plasma IgEbetween the control and study groups.DeliverablesFenretinide has been demonstrated to have great poten-tial as a therapeutic agent. Our findings provide a novelapproach to treat allergen-induced asthma and will helpus in pursuing these studies towards the use of thisdrug for patients suffering from allergic asthma.RelevanceThe data presented herein will facilitate the develop-ment of fenretinide as a therapeutic compound in thetreatment of allergic asthma and provide the foundationfor the identification of drug targets for the developmentof effective future drugs.
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 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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".