The Effect of the Immunosuppressant Drug, Tacrolimus, on Nitric Oxide Production in the Immortalized First Trimester Extra-Villous Trophoblast Cells
Bibliographic record
Abstract
The remodeling of uterine spiral arteries and subsequent placental formation are crucial for normal growth and development of the fetus. These processes are heavily dependent on the functioning of the extra-villous trophoblast cells and their ability to invade into the maternal decidual blood vessels. Reduced trophoblast invasion and shallow spiral artery remodeling can lead to a number of gestational complications including intrauterine growth restriction (IUGR). Therapeutic intervention with low dose immunosuppressant tacrolimus was able to prevent implantation failure and IUGR in obese and diabetic mice. Treatment with tacrolimus successfully aided in spiral artery modification that was conducive to a successful pregnancy. Further, tacrolimus has shown promise in restoring trophoblast cell functioning in the immortalized first trimester HTR8/SVneo extra-villous trophoblast cells cultured under preeclampsia-like conditions in vitro. However, the mode of action of tacrolimus has yet to be elucidated. Here we attempt to uncover the mode of action of tacrolimus by examining its effects on eNOS activity within the trophoblast cells. Cells were treated with tacrolimus (10 ng/mL), L-NAME (40 nM/mL) or a combination of both and subjected to analysis by several functional assays. The data obtained in this study is suggesting that L-NAME treatment has inhibitory effects on the levels of the pPGR, pSTAT3 and NO within the HTR8/SVneo cells. The use of low-dose tacrolimus abrogated the suppressive effect of L-NAME and restored the levels of the pPGR, pSTAT3, and NO within the cells.
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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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| 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".