ArticleCommunications biology2022
Artificial intelligence-rationalized balanced PPARα/γ dual agonism resets dysregulated macrophage processes in inflammatory bowel disease.
Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 18 citations in OpenAlex.
- Pharmacological Targeting of Peroxisome Proliferator-activated Receptors for Prevention of Radiation-induced Cognitive Decline.Annals of neurosciences · 2026Review
- New approach methodologies in Crohn's disease link molecular disease subtypes to clinical outcomes.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Artificial intelligence and digital transformation of gastroenterology and hepatology: A critical review of clinical applications and future challenges.World journal of hepatology · 2026Review
- Dysfunction of mitochondria in intestinal epithelial cells: a key player in the pathogenesis of inflammatory bowel diseases.Gastroenterology report · 2026Review
- Peroxisome proliferator-activated receptors in inflammatory bowel disease: linking immunometabolism, lipid signaling, and therapeutic potential.Intestinal research · 2026Review
- From tissue to blood: an integrated multi-omics signature identifies fibrogenesis and neutrophil activation as key drivers of ulcerative colitis severity.Frontiers in immunology · 2026Article
- Integrating Animal Experiments, Bioinformatics and Molecular Dynamics Stimulations to Explore the Potential Mechanism of Songyang Duanwu Tea Improving Metabolic Syndrome.Combinatorial chemistry & high throughput screening · 2026Article
- Distinct colitis-associated macrophages drive NOD2-dependent bacterial sensing and gut homeostasis.The Journal of clinical investigation · 2025Article
- Probing and manipulating the gut microbiome with chemistry and chemical tools.Gut microbiome (Cambridge, England) · 2025Review
- A living organoid biobank of patients with Crohn's disease reveals molecular subtypes for personalized therapeutics.Cell reports. Medicine · 2024Article
- Advancing therapeutic frontiers: a pipeline of novel drugs for luminal and perianal Crohn's disease management.Therapeutic advances in gastroenterology · 2024Review
- Peroxisome Proliferator-Activated Receptor-Targeted Therapies: Challenges upon Infectious Diseases.Cells · 2023Review
- Impact of artificial intelligence on prognosis, shared decision-making, and precision medicine for patients with inflammatory bowel disease: a perspective and expert opinion.Annals of medicine · 2023Review
- The PPARα Regulation of the Gut Physiology in Regard to Interaction with Microbiota, Intestinal Immunity, Metabolism, and Permeability.International journal of molecular sciences · 2022Review
- Partial Synthetic PPARƳ Derivative Ameliorates Aorta Injury in Experimental Diabetic Rats Mediated by Activation of miR-126-5p Pi3k/AKT/PDK 1/mTOR Expression.Pharmaceuticals (Basel, Switzerland) · 2022Article
- The role of cholesterol and mitochondrial bioenergetics in activation of the inflammasome in IBD.Frontiers in immunology · 2022Review
- Parsing the Role of PPARs in Macrophage Processes.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
A computational platform, Boolean network explorer (BoNE), has recently been developed to infuse AI-enhanced precision into drug discovery; it enables invariant Boolean Implication Networks of disease maps for prioritizing high-value targets. Here we used BoNE to query an Inflammatory Bowel Disease (IBD)-map and prioritize a therapeutic strategy that involves dual agonism of two nuclear receptors, PPARα/γ. Balanced agonism of PPARα/γ was predicted to modulate macrophage processes, ameliorate colitis, 'reset' the gene expression network from disease to health. Predictions were validated using a balanced and potent PPARα/γ-dual-agonist (PAR5359) in Citrobacter rodentium- and DSS-induced murine colitis models. Using inhibitors and agonists, we show that balanced-dual agonism promotes bacterial clearance efficiently than individual agonists, both in vivo and in vitro. PPARα is required and sufficient to induce the pro-inflammatory cytokines and cellular ROS, which are essential for bacterial clearance and immunity, whereas PPARγ-agonism blunts these responses, delays microbial clearance; balanced dual agonism achieved controlled inflammation while protecting the gut barrier and 'reversal' of the transcriptomic network. Furthermore, dual agonism reversed the defective bacterial clearance observed in PBMCs derived from IBD patients. These findings not only deliver a macrophage modulator for use as barrier-protective therapy in IBD, but also highlight the potential of BoNE to rationalize combination therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.