PMN-MDSC-derived Activin A mediates Cancer-associated cardiomyopathy 4132
Bibliographic record
Abstract
Abstract Description Introduction Cachexia stands as a significant contributor to cancer-related death. Cachectic patients suffer from wasting of cardiac and skeletal muscles. We previously demonstrated the role of suppressive tumour-induced neutrophils in cardiac and skeletal muscle atrophy and dysfunction in mouse models. These cells were found to be a major source of activin A, a cytokine of the myostatin family. Methodology: Mice were injected with a murine Lewis Lung Carcinoma cell line and euthanized after 2 weeks to assess cachexia and immune cell activation. To elucidate the mechanistic contribution of Activin A-producing PMNs to cachexia, we utilized a myeloid (LysM Cre) and PMN (Ly6G Cre) -specific deletion of activin A. Results Myeloid and PMN-specific deletion of the Activin A gene protected against cardiac wasting; however, it did not impact the infiltration of these cells. Western blot confirmed Activin A to phosphorylate Smad2/3 in the heart. RNA seq analysis of muscle tissue in tumour-bearing mice revealed an upregulation of mitophagy and protein degradation markers and inhibition of oxidative phosphorylation. Knocking out Activin A gene in PMNs reversed these effects and guarded against muscle loss under tumour burden. Conclusions We demonstrate that PMNs produce activin A that induces cardiac dysfunction by triggering pathways of protein degradation and altering energy production. Funding Sources Canadian Institutes of Health Research grant# RES0052619 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.010 | 0.002 |
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".