NAD <sup>+</sup> depletion is central to placental dysfunction in an inflammatory subclass of preeclampsia
Bibliographic record
Abstract
Preeclampsia (PE) is a hypertensive disorder of pregnancy and a major cause of maternal/perinatal adverse health outcomes with no effective therapeutic strategies. Our group previously identified distinct subclasses of PE, one of which exhibits heightened placental inflammation (inflammation-driven PE). In non-pregnant populations, chronic inflammation is associated with decreased levels of cellular NAD + , a vitamin B3 derivative involved in energy metabolism and mitochondrial function. Interestingly, specifically in placentas from women with inflammation-driven PE, we observed the increased activity of NAD + -consuming enzymes, decreased NAD + content, decreased expression of mitochondrial proteins, and increased oxidative damage. HTR8 human trophoblasts likewise demonstrated increased NAD + -dependent ADP-ribosyltransferase (ART) activity, coupled with decreased mitochondrial respiration rates and invasive function under inflammatory conditions. Such adverse effects were attenuated by boosting cellular NAD + levels with nicotinamide riboside (NR). Finally, in an LPS-induced rat model of inflammation-driven PE, NR administration (200 mg/kg/day) from gestational days 1–19 prevented maternal hypertension and fetal/placental growth restriction, improved placental mitochondrial function, and reduced inflammation and oxidative stress. This study demonstrates the critical role of NAD + in maintaining placental function and identifies NAD + boosting as a promising preventative strategy for PE.
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How this classification was reachedexpand
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 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".