Dolutegravir Inhibits Autophagy In Vitro in a Mouse Blood–Brain Barrier Model
Bibliographic record
Abstract
Despite the effectiveness and tolerability of antiretroviral therapy (ART) in treating HIV infection, integrase strand transfer inhibitors, particularly dolutegravir (DTG)-based ART, have been associated with various brain complications. Our research group has previously reported that DTG disrupts the blood-brain barrier (BBB) by inducing endoplasmic reticulum (ER) stress. To further understand DTG-associated toxicity, this follow-up study assessed autophagy dysfunction, a critical process that is closely linked to ER stress, using primary cultures of mouse brain microvascular endothelial cells as a robust BBB rodent model. We demonstrated that DTG exposure at therapeutically relevant concentrations significantly increased Sqstm/p62, LC3B-I and LC3B-II protein expression, and downregulated autophagy-related genes Ulk1 and Atg14, suggesting an autophagy inhibition as a result of DTG treatment. This study provides new insights into the toxicological mechanisms of DTG and pathogenesis of DTG-associated brain complications.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 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 | 0.002 |
| 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".