Human mesenchymal stem cell transplantation changes proinflammatory gene expression through a nuclear factor‐κB‐dependent pathway in a rat focal cerebral ischemic model
Bibliographic record
Abstract
Previous studies have demonstrated the immunomodulatory functions of mesenchymal stem cells (MSCs) in cerebral ischemic rats. However, the underlying mechanisms are unclear. The purpose of this study is to investigate the effects of MSC transplantation on transcriptional regulations of proinflammatory genes in cerebral ischemia. Transient ischemia was induced by middle cerebral artery occlusion (MCAO) in adult male Sprague-Dawley rats. After 24 hr, vehicle (PBS) or a human MSC line (B10) was transplanted intravenously. The neurological deficits, infarct volume, cellular accumulations, and gene expression changes were monitored by means of behavior tests, MRI, immunohistochemistry, Western blotting, laser capture microdissection, and real-time PCR. In the core area of the B10 transplantation group, the number of ED1-positive macrophage/microglia was decreased compared with the PBS group. In the core, nuclear factor-κB (NF-κB) was decreased, although CCAAT/enhancer-binding protein β was not changed; both were expressed mainly in ED1-positive macrophage/microglia. Likewise, mRNAs of NF-κB-dependent genes including interleukin-1β, MCP-1, and inducible nitric oxide synthase were decreased in ED1-positive and Iba-1-positive macrophage/microglia in the B10 transplantation group. Moreover, upstream receptors of the NF-κB pathway, including CD40 and Toll-like receptor 2 (TLR2), were decreased. Immunofluorescence results showed that, in the B10 transplantation group, the percentages of NF-κB-positive, CD40-positive, and TLR2-positive cells were decreased in ED1-positive macrophage/microglia. Furthermore, NF-κB-positive cells in the CD40- or TLR2-expressing cell population were decreased in the B10 transplantation group. This study demonstrates that B10 transplantation inhibits NF-κB activation, possibly through inhibition of CD40 and TLR2, which might be responsible for the inhibition of proinflammatory gene expression in macrophage/microglia in the infarct lesion.
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) | 0.000 | 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 | 0.001 |
| 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".