Insulin Signaling Suppresses Virus Replication and Neuroinflammation in HIV/AIDS (S53.005)
Bibliographic record
Abstract
Objective: To investigate the effects of insulin receptor activation using in vitro and in vivo models of HAND. Background: HIV/AIDS results in neuroinflammation with HIV-associated neurocognitive disorder (HAND) in over 25[percnt] of patients despite available antiretroviral therapy. Experimental studies report insulin treatment suppresses inflammation and HIV-1 replication in leukocytes. Methods: Cerebral white matter from HIV-infected and uninfected patients was investigated using molecular and morphological analyses. Primary human microglia were infected with HIV-1 and treated with/without insulin for 5 days, followed by analyses of viral production and host responses. Primary human neurons were exposed to HIV-1 Vpr and treated with/without insulin followed by cytotoxicity assays. Feline immunodeficiency virus (FIV)-infected cats were treated daily for 6 weeks with intranasal (IN) insulin or vehicle (PBS) with subsequent neurobehavioral, molecular and neuropathological analyses. Results: Increased neuroinflammatory gene expression (e.g., IL-6, CXCL10, MHC Class II) was evident but PPAR-γ expression was suppressed in brains from patients with HIV encephalitis (p<0.05). Similar expression of insulin and IGF-1 receptors was evident on glia and neurons in each clinical group. HIV-infected microglia showed reduced supernatant HIV-1 p24 levels during insulin treatment (p<0.05), which was accompanied by reduced CXCL10 and IL-6 transcript levels; conversely, insulin induced PPAR-γ expression in HIV-infected microglia. Insulin treatment of neurons prevented neuronal injury caused by HIV-1 Vpr-mediated cytotoxicity (p<0.05). Insulin (IN) treatment suppressed CXCL10 and IL-6 expression in brains of FIV-infected animals (p<0.05). Reduced FIV transcript (pol) and protein (gag) levels and increased PPAR-γ levels (p<0.05) were observed in brains of insulin-treated FIV-infected animals, which was accompanied by reduced gliosis. Insulin (IN) therapy in FIV-infected animals improved neurological status including both memory and motor performances (p<0.05). Conclusions: Insulin receptor signaling exerts antiviral and anti-inflammatory actions with potential therapeutic effects on the brain and might serve as a valuable adjunct treatment for HAND.
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
Direct model labels (unvalidated)
Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.
| Model arm | Categories | Study design | Confidence |
|---|---|---|---|
| gemma | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Bench or experimental | low |
| gpt | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Bench or experimental | high |
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) | 0.003 | 0.001 |
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, unvalidatedLabeled directly by 2 models reading the full record.
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".