Effects of lipid core nanoparticles-associated methotrexate on cardiac remodeling and skeletal muscle inflammatory markers in infarcted rats
Bibliographic record
Abstract
Abstract Introduction After myocardial infarction (MI), necrotic cardiomyocytes release substances that sensitize nucleotide binding receptors (NLRs) responsible for forming and activating inflamassomes, multiproteic platforms involved in acute inflammation. Although inflammation is useful after heart injury, its persistence may cause deleterious effects in both cardiac and skeletal muscle. The presence of inflamassomes in skeletal muscles after MI has not been established. Methotrexate (MTX) is a potent immunosuppressive drug. Its association with lipid core nanoparticles (MTX-LDE) has shown beneficial effects on cardiac remodeling in infarcted rats. Purpose To evaluate the effects of early MTX-LDE administration on cardiac remodeling and inflammatory markers of infarcted rat soleus muscle. Methods Male Wistar rats were subjected to MI or sham surgery and separated into Sham (n=11), MI (n=11) and MI-MTX (n=14) groups. MI-MTX was initiated 24 h after MI at 1 mg/kg/week, intraperitoneally, for 10 weeks. Only rats with infarction size > 35% total left ventricle (LV) area were included in the study. Echocardiogram was performed at the end of the study. Soleus protein and gene expression of NLRP1, NLRP3, NLRC4, apoptosis-associated speck-like protein containing a CARD (ASC), pro-caspase-1, caspase-1, pro-interleukin (IL)-1 beta, and IL-1 beta were quantified by Western blotting and qPCR, respectively. Statistical analysis: Student t test, ANOVA, and Bonferroni. Results Infarct size did not differ between groups (MI 43 ± 6.2; MI-MTX 43 ± 5.6 % total LV area; p>0.05). Echocardiographic data are shown in the Table. NLRP1 (Sham 1.00 ± 0.34; MI 0.62 ± 0.31; MI-MTX 0.50 ± 0.05* arbitrary units; *p<0.05 vs Sham) and NLRC4 (Sham 1.00 ± 0.29; MI 0.71 ± 0.36; MI-MTX 0.54 ± 0.09* arbitrary units; *p<0.05 vs Sham) protein expression was lower in MI-MTX than Sham. NLRP3, ASC, pro-caspase-1, caspase-1, pro-IL-1 beta, and IL-1 beta protein and gene expression did not differ between groups. Conclusion Early methotrexate administration in lipid core nanoparticles reduces soleus NLRP1 and NLRC4 protein expression despite no improvement in cardiac remodeling in infarcted rats.Echocardiographic data
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 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) | 0.000 | 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 teacher head, 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".