Specialized Pro-resolving Lipid Mediators: Modulation of Diabetes-Associated Cardio-, Reno-, and Retino-Vascular Complications
Bibliographic record
Abstract
Diabetes and its associated chronic complications present a healthcare challenge on a global scale. Despite improvements in the management of chronic complications of the micro-/macro-vasculature, their growing prevalence and incidence highlights the scale of the problem. It is currently estimated that diabetes affects 425 million people globally and it is anticipated that this figure will rise by 2025 to 700 million people. The vascular complications of diabetes including diabetes-associated atherosclerosis and kidney disease present a particular challenge. Diabetes is the leading cause of end stage renal disease, reflecting fibrosis leading to organ failure. Moreover, diabetes associated states of inflammation, neo-vascularization, apoptosis and hypercoagulability contribute to also exacerbate atherosclerosis, from the metabolic syndrome to advanced disease, plaque rupture and coronary thrombosis. Current therapeutic interventions focus on regulating blood glucose, glomerular and peripheral hypertension and can at best slow the progression of diabetes complications. Recently advanced knowledge of the pathogenesis underlying diabetes and associated complications revealed common mechanisms, including the inflammatory response, insulin resistance and hyperglycemia. The major role that inflammation plays in many chronic diseases has led to the development of new strategies aiming to promote the restoration of homeostasis through the "resolution of inflammation." These strategies aim to mimic the spontaneous activities of the 'specialized pro-resolving mediators' (SPMs), including endogenous molecules and their synthetic mimetics. This review aims to discuss the effect of SPMs [with particular attention to lipoxins (LXs) and resolvins (Rvs)] on inflammatory responses in a series of experimental models, as well as evidence from human studies, in the context of cardio- and reno-vascular diabetic complications, with a brief mention to diabetic retinopathy (DR). These data collectively support the hypothesis that endogenously generated SPMs or synthetic mimetics of their activities may represent lead molecules in a new discipline, namely the 'resolution pharmacology,' offering hope for new therapeutic strategies to prevent and treat, specifically, diabetes-associated atherosclerosis, nephropathy and retinopathy.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 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 | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".