p55PIK deficiency and its NH<sub>2</sub>-terminal derivative inhibit inflammation and emphysema in COPD mouse model
Bibliographic record
Abstract
Chronic obstructive pulmonary disease (COPD) is composed of chronic airway inflammation and emphysema. Recent studies show that Class IA phosphatidylinositol 3-kinases (PI3Ks) play an important role in the regulation of inflammation and emphysema. However, there are few studies on their regulatory subunits. p55PIK is a regulatory subunit of Class IA PI3Ks, and its unique NH2-terminal gives it special functions. p55PIK expression in the lungs of nonsmokers, smokers, and patients with COPD was examined. We established a fusion protein TAT-N15 from the NH2-terminal effector sequence of p55PIK and TAT (the transduction domain of HIV transactivator protein) and investigated the effects of silencing p55PIK or adding TAT-N15 on cigarette smoke exposure at the cellular and animal level. p55PIK expression was increased in patients with COPD. p55PIK deficiency and TAT-N15 significantly inhibited the cigarette smoke extract-induced IL-6, IL-8, and activation of the Akt and the NF-κB pathway in BEAS-2B. p55PIK deficiency and TAT-N15 intranasal administration prevented emphysema and the lung function decline in mice exposed to smoke for 6 mo. p55PIK deficiency and TAT-N15 significantly inhibited lung inflammatory infiltration, reduced levels of IL-6 and KC in mice lung homogenate, and inhibited activation of the Akt and the NF-κB signaling in COPD mice lungs. Our studies indicate that p55PIK is involved in the pathogenesis of COPD, and its NH2-terminal derivative TAT-N15 could be an effective drug in the treatment of COPD by inhibiting the activation of the Akt and the NF-κB pathway.
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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 | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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, 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".