148 2‐Methoxyestradiol, an Endogenous Estrogen Metabolite, Regulates Apoptosis in Skin Microvascular Endothelial Cells
Bibliographic record
Abstract
Programmed cell death or apoptosis regulates the sequence of cellular events that are involved in the wound healing process. Understanding the mechanisms controlling apoptosis during tissue repair may lead to the development of modalities to improve healing and reduce scarring. 2‐Methoxyestradiol (2ME), a naturally occurring metabolite of 17‐ estradiol, has recently emerged as a promising anti‐proliferative and angiostatic agent with minimal toxicity at pharmacological doses. However, the mechanism by which 2ME induces its anti‐proliferative and apoptotic activities is uncertain, and its physiological function remains to be determined. In the present study we examined the effects of physiological and pharmacological concentrations 2ME in human skin microvascular endothelial cells. Our findings show that 2ME rapidly activates JNK and p38 MAP kinase pathways at both physiological and supraphysiological levels. Our results indicate that the rapid activation of p38 and JNK are not required for 2ME‐induced inhibition of DNA synthesis, caspase‐3 activation, or cell cycle arrest, and thus apoptosis, in microvascular endothelial cells. On the contrary, our results suggest that rapid activation of JNK and p38 MAP kinases likely mediates an early pro‐survival response to 2ME. The fine regulation of survival versus apoptotic signals may contribute to the ability of 2ME to elicit its effects in endothelial cells. Since endothelial cells play an essential role during wound healing, identification 2ME as a potent regulator of endothelial cell proliferation and function warrants further studies of its therapeutic potential as an agent to manipulate wound repair events.
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 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 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".