The Toll-like Receptor 9 Ligand CPG-C Attenuates Acute Inflammatory Cardiac Dysfunction
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Bibliographic record
Abstract
Stimulation of toll-like receptor 9 (TLR9) by CpG-C containing oligonucleotides attenuates ischemic injury in the brain and liver. In this study, we investigate whether any of the three classes of CpG (A, B, or C) mitigate ischemia-induced cardiac dysfunction. We measured left ventricular ejection fraction (LVEF) in C57BL/6 mice using transthoracic echocardiography. Using LPS as an inflammatory stimulus, CpG-C was uniquely able to prevent cardiac dysfunction; its activity was confirmed through nuclear factor κB transcriptional activity assay in HL-1 cardiomyocytes. We went on to investigate CpG-C's efficacy and mechanism in the treatment of ischemia-reperfusion. Compared with baseline, no class of CpG significantly altered LVEF at 6 or 24 h; 40 mg/kg LPS induced a rapid, profound suppression of LVEF compared with baseline (26% ± 1.4% vs. 65% ± 1.4%), whereas pretreatment with CpG demonstrated that of the three classes, only CpG-C prevented the LPS -induced decrease in LVEF (51% ± 5.8%). In separate mice, 1-h ischemia followed by reperfusion of the left anterior descending artery resulted in a 7-day suppression of the LVEF (66% ± 5.2% at baseline; 46% ± 4.7% at day 1, and 46% ± 4.0% at day 7), whereas mice either pretreated with or begun on an infusion of CpG-C during the ischemia had no significant decline in LVEF. Gene expression microarray of CpG-C-stimulated cells revealed upregulation of the nuclear factor κB pathway inhibitors TNFAIP3, NFKBIA, TRIM30, and TNIP1. These may play a role in attenuation of cardiac inflammation. The TLR9 ligand CpG-C attenuates the acute inflammatory cardiac dysfunction induced by both LPS and ischemia-reperfusion of the left anterior descending artery.
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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 | 0.000 | 0.000 |
| 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.004 |
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 it