Distinct interactions of proanthocyanidins of various degrees of polymerization with TLR4 receptor on the integrity of differentiating Caco-2 cell monolayers through tight junction protein expression
Bibliographic record
Abstract
Many studies have demonstrated the potential of proanthocyanidins (PACs) to protect the intestinal epithelial barrier by regulating the cellular levels of tight junction (TJ) proteins. The effects of five PAC fractions with different mean degrees of polymerization (DP), namely, DT-PAC (dimers - trimers), OPAC-1 (oligomeric-PAC, pentamer - hexamer), OPAC-2 (octamer - dodecamer), PPAC-1 (polymeric-PAC, 13-15 subunits), and PPAC-2 (20 subunits), on the barrier integrity of differentiating Caco-2 cell monolayers were investigated. The effects of PAC fractions on the integrity of Caco-2 monolayers were evaluated by measuring the permeability of fluorescein isothiocyanate (FITC)-dextran and cellular levels of TJ proteins by western blotting. DT-PAC fraction favored the barrier integrity by significantly increasing the cellular protein levels of barrier-forming zonula occludens-1 (ZO-1) and claudin-3. The effects of OPAC fractions were controversial as the treatments simultaneously increased the cellular protein levels of barrier-forming claudin-1 and pore-forming claudin-2. The PPAC fractions significantly increased the permeation of FITC-dextran through Caco-2 monolayers, indicating a loss in barrier integrity. PPAC fractions disrupted the barrier integrity by reducing the cellular protein levels of barrier-forming ZO-1 and claudin-3 while increasing the pore-forming claudin-2. Molecular docking experiments revealed that PAC molecules with higher DP may disrupt Caco-2 monolayers by stimulating the cell surface toll-like receptor 4 (TLR4). Interestingly, PAC molecules with lower DP may inhibit the activation of TLR4 signaling. Highly polymerized PACs may disrupt the barrier integrity of intestinal epithelium undergoing differentiation by suppressing barrier-forming and upregulating the pore-forming TJ proteins, while less polymerized PACs protect barrier integrity by depicting opposing effects.
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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".