In vivo and In vitro PPAR-y Activation Decreases M1-Macrophage Polarization and Improves Liver Ischemia Reperfusion Injury
Bibliographic record
Abstract
Background M1-Macrophage polarization has been studied as a potential target to decrease inflammatory response in sepsis and inflammation related diseases. Its role in the setting of inflammatory response during liver ischemia reperfusion injury is unknown. Material a nd Methods First, for in vitro experiments mouse peritoneal macrophages (PM) were stimulated with LPS+INFy to achieve M1-polarization. PMs received Rosiglitazone (RGZ-PPARy-agonist) or vehicle (Ctrl) 1hr before and then together with LPS+INFy and were incubated for 24hrs. For in vivo experiments, the groups underwent partial liver ischemia (70% of liver) and received RGZ or vehicle 24hr and 1hr prior to reperfusion. Liver samples were taken prior and following reperfusion (BL, 1hr, 6hr and 24hr) and were analyzed for apoptosis and necrosis with TUNEL and H&E staining, respectively. In vitro and In vivo (Liver) M1-macrophage polarization was evaluated by intracellular nitric oxide (NO) production and assessed with fluorescence (RFU-Relative fluorescence units) and flowcytometry, (MFI-Mean Fluorescence Intensity), respectively. Results In vitro PPARy activation resulted in a significant reduction of NO production (M1-polarization) in the RGZ vs Ctrl group at 24hrs after stimulation (67238±6580 RFU vs 101310±7552 RFU, p< 0.01)(A). In vivo PPARy activation prior to reperfusion significantly reduced NO production (M1-Kupffer cell polarization) in the RGZ vs Ctrl group at 6hr (1469±340 MFI vs 3069±779 MFI, p< 0.01) and 24hr (762±340 MFI vs 1074±198 MFI, p=0.04) following reperfusion (B). TUNEL staining analysis showed significant reduction in the RGZ vs Ctrl group at 6hr after reperfusion (26.40±2.93 vs 50.13±8.29%; p=0.04). H&E staining revealed almost 50% reduction in the degree of necrosis in RGZ vs Ctrl group (26.66±4.78 vs 45.62±4.57%; p=0.03)(C). Conclusion PPAR-y activation prior to reperfusion improves the deleterious effect of liver reperfusion injury by decreasing M1-macrophage polarization.
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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 | 0.000 | 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) | 0.002 | 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".