Methylglyoxal-induced increase in peroxynitrite and inflammation related to diabetes
Bibliographic record
Abstract
Methylglyoxal (MG) is a reactive α-oxoaldehyde and a glucose metabolite.Previous studies in our laboratory have shown that MG induces the production of reactive oxygen species (ROS), such as superoxide (O 2 .-),nitric oxide (NO) and peroxynitrite (ONOO -), in vascular smooth muscle cells (VSMCs, A-10 cells).However, the effect of endogenous MG and mechanisms of MG-induced oxidative stress have not been thoroughly explored.The present study investigated fructose (a precursor of MG)induced ONOO -formation in A-10 cells and whether this process was mediated via endogenous MG formation; roles of MG in regulating mitochondrial ROS (mtROS) production and mitochondrial functions in A-10 cells; and effect of MG on neutrophils in patients with type 2 diabetes mellitus (T2DM).Fructose induced intracellular production of MG in a concentration-and time-dependent manner.A significant increase in the production of NO, O 2 .-, and ONOO -was observed in the cells exposed to fructose or MG.Fructose-or MG-induced ONOO -generation was significantly inhibited by MG scavengers and by O 2 .-or NO inhibitors.The data showed that fructose treatment increased the formation of ONOO -via increased NO and O 2 .-production in A-10 cells, and this effect was directly mediated by an elevated intracellular concentration of MG.By inhibiting complex III and manganese superoxide dismutase activities, MG induced mitochondrial overproduction of O 2 .-, and mitochondrial ONOO -further.MG also reduced mitochondrial ATP synthesis, indicating the dysfunction of mitochondria.In addition, MG increased plasma NO levels in patients with T2DM, which reflected the oxidative status in those patients.MG-induced oxidative stress in patients with T2DM significantly enhanced levels of cytokines released from neutrophils.Moreover, the CHAPTER 2: GENERAL METHODOLOGY………………………………….
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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 | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".