Lipocalin 2 mediated hypoferremia protects against endotoxin- induced sepsis in mice (112.11)
Bibliographic record
Abstract
Abstract Sepsis is characterized by hypoferremia, a primitive protective mechanism to limit iron-induced oxidative stress. Lipocalin-2 (Lcn2) which is highly upregulated during inflammation and has been shown to transport iron under physiologic conditions. Accordingly, we hypothesized that such upregulation of Lcn2 serves to protect against sepsis associated oxidative stress. Lcn2 deficient mice (Lcn2KO) and their WT littermates were given E. coli LPS (20mg/kg BW) i.p. and monitored for mortality. Serum TNFα, IL-18, LDH, aminotransferases, iron, glutathione and cysteine were analyzed. Splenocyte apoptosis was assayed by TUNEL, caspase 3 cleavage and flow cytometry. In WT mice, LPS-induced systemic Lcn2 peaked at 24h and returned to basal levels by 48h. All Lcn2KO died by day 8 while only 20% mortality was observed in WT mice. In addition, Lcn2KO exhibited substantial elevation of every parameter tested including both pro- and anti-inflammatory cytokines. Further,Lcn2KO splenocytes exhibited extensive apoptosis as measured by caspase 3 cleavage, TUNEL staining and flow cytometry. More importantly, when compared to WT mice, Lcn2KO mice failed to exhibit LPS-induced hypoferremia at early time points and exhibited severe hepatic oxidative stress. Our data demonstrate that Lcn2 facilitates LPS-induced hypoferremia and serves as a host protective factor by reducing oxidative stress. Given Lcn2 multifunctionality, it may be developed as a potential therapeutic agent to treat sepsis.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".