Abstract 36: Elevated Expression of Dual Oxidases (Duox) Under Ischemic Conditions Contributes to Oxidative Stress and Decreased Cell Viability.
Bibliographic record
Abstract
Introduction: Redox imbalance during ischemia/reperfusion Injury in the brain following focal ischemic stroke is associated with impaired neurological functions. Following ischemia/reperfusion, there is a burst of oxidative stress/reactive oxygen species (ROS). ROS physiologically serve as signaling molecules but excessive amounts of ROS contribute to destruction of endothelial integrity, blood brain barrier disruption, and neuronal cell death. NADPH oxidases (NOX) are important sources of ROS during ischemic stroke. Dual oxidases (Duox) are new members of NOX family and are known for directly generating hydrogen peroxide/ROS. Role of Duox following brain ischemic injury has been little investigated. Methods: Ischemia was induced by middle cerebral artery occlusion (MCAO) and reperfusion. In vitro ischemia was generated by oxygen-glucose deprivation (OGD). Expression was analysed by western blot analysis, RT-PCR, Immunofluorescence staining. ROS was measured by dichloro-dihydrofluorescein staining. Results: Our preliminary studies for the first time have identified that expression of Duox are spatially and temporally regulated in ipsilateral hemisphere of spontaneously hyertensive rat brains following MCAO and reperfusion. Expression of Duox 1 was up-regulated about 2 folds after 3 days, and16 folds after 7 days of reperfusion. Its expression was further increased to about 30 folds at day 21 after reperfusion. The expression of Duox 1 was specifically up-regulated in activated astrocytes and VWF and CD31 positive endothelial cells indicating its presence in blood vessels. In support of these in vivo observations, Duox1 expression was significantly increased in astrocytes and endothelial cell cultures exposed to either ATP or OGD. Duox1 expression was associated with increased ROS production and decreased cell viability. However, pre-treatment with Duox1 specific siRNA decreased the ROS production and increased the cell viability by about 30 percent. Summary: Up-regulation of Duox under ischemic/reperfusion conditions suggests that this enzyme potentially contributes to excessive ROS production. Further studies targeting these novel oxidases may open up a promising approach to reduce brain injury after stroke.
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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) | 0.000 | 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) | 0.003 | 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, 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".