Prolong Allograft Survival by Silencing mTOR Gene Using Mannose Liposome in Heart Transplantation.
Bibliographic record
Abstract
Background: The mammalian target of rapamycin (mTOR) is one of the most critical signaling kinases that controls dendritic cells (DCs) and T cells function. RNA interference based therapy is a novel strategy for prolonging allograft survival. DCs abundantly express mannose receptor. We hypothesized that blocking the mTOR pathway using mannose liposome with small interference RNA (siRNA) target mTOR gene, can specifically deliver siRNA to DCs block mTOR pathway and may prolong allogeneic heart graft survival. Method: Mannose liposome with mTOR siRNA (Man-mTOR) was prepared. Recipients (BALB/c mice) were treated with Man-mTOR, 3 and 7 days prior to heart transplantation and 7, 14, 21 days after transplantation. Control groups were injected with mannose liposome with scramble siRNA (Man-Gl2) and liposome without mannose (without Man-mTOR). After siRNA treatment, a fully MHC-mismatched (C57/BL6 to BALB/c) heart transplantation was performed. Result: Mannose liposome can specific deliver mTOR siRNA to the spleen APCs, the fluorescence of Cy3-labeled siRNA and gene silencing efficiency can be confirmed by western blot. Man-mTOR treatment significantly prolonged allogeneic heart graft survival (mean survival time MST=56.2 days). In contrast, MST of allogenic hearts in recipients treated with Man-Gl2 and without Man-mTOR was 6.3 days and 17.5 days respectively. Flow cytometric analysis showed an upregulation of FoxP3 expression in spleen lymphocytes and a concurrent downregulation of CD40 and CD86 expression in splenic DCs of Man-mTOR treated mice. An MLR, using splenic DCs isolated from Man-mTOR treated recipients, showed lower T cell proliferation capacity and lower level of INF-γ, IL1-β and higher level of IL-10 and IL-6, compared to control groups. Finally, tissue histopathology demonstrated an overall reduction in lymphocyte interstitium infiltration, vascular obstruction, and edema in mice treated with Man-mTOR. Conclusion: This study demonstrated that use mannose liposome specifically deliver siRNA to the spleen DCs silencing of mTOR gene can prolong allograft survival, and may provide a novel and more effective RNAi based anti-rejection regimen in heart transplantation.
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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 | 0.000 | 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) | 0.001 | 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 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".