8D.01
Bibliographic record
Abstract
Objective: The renin-angiotensin system (RAS) has been known for more than a century as a cascade that regulates body fluid balance, renal functions and blood pressure. Angiotensin-converting enzyme 2 (ACE2) is now known as a negative regulator of RAS, and activation of the ACE2 is a possible alternative target for new drugs, since some protective influences on renal and cardiovascular function have been revealed. We hypothesized that ACE2 would exert beneficial effects on oxidative stress levels and renal injury in apolipoprotein E (ApoE) -knockout (KO) mice. Design and method: In this study, we used 12-week-old wild-type, ApoEKO, and ACE2/ApoE double KO mice. The ApoEKO mice were treated with recombinant human ACE2 (hrACE2) with the daily dose of 2 mg/kg. We characterized the functional, structural and molecular signaling changes in mice kidneys. Results: Compared with the ApoEKO mice, ACE2 deficiency led to greater increases in renal oxidative stress levels and expression of oxidative stress-inducible proteins NADPH oxidase 4 (NOX4) in the ACE2/ApoE double KO mice. These changes were associated with exacerbation of renal tubule ultrastructure injury and greater activation of Akt and ERK1/2 phosphorylated signaling. Conversely, treatment with hrACE2 significantly attenuated renal oxidative stress levels and ultrastructure injury, and prevented the expression of NOX4 and phosphorylated level of Akt and ERK1/2 in ApoEKO mouse kidneys. However, there were no changes in renal expression of NOX2 and Mas receptor among groups. Conclusions: Deletion of ACE2 triggers greater increases in renal oxidative stress and tubular ultrastructure injury in the ACE2/ApoE double mutant mice with greater activation of Akt-ERK1/2 phosphorylated signaling. While ACE2 overexpression alleviates renal tubular injury in ApoE-mutant mice with suppression of superoxide generation and downregulation of the Akt-ERK phosphorylated signaling. Strategies aimed at enhancing ACE2 action may have important therapeutic potential for atherosclerosis and renal diseases.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.006 | 0.001 |
| Open science | 0.002 | 0.004 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.903 | 0.836 |
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".