ArticleSignal transduction and targeted therapy2026
Nanotherapeutic macrophage reprogramming through immunometabolic and microbial modulation for sepsis treatment.
Article in Signal transduction and targeted therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
Abstract
Sepsis is a life-threatening syndrome characterized by dysregulated immune responses and metabolic dysfunction, and remains a major cause of global mortality. While nanomedicine offers new opportunities for sepsis therapy, current strategies rarely achieve comprehensive modulation of macrophage immunometabolism and microenvironmental signaling. Here, we develop a glutathione-responsive nanotherapeutic platform (EONPs) by conjugating the stimulator of interferon genes (STING) inhibitor 4-octyl itaconate to polyethylene glycol, followed by encapsulation of the dihydroorotate dehydrogenase (DHODH) inhibitor EA6. Integrated transcriptomic, metabolomic, and metagenomic analyses combined with pharmacological assessments reveal that EONPs suppress systemic hyperinflammation, reprogram macrophages toward an anti-inflammatory phenotype, restore gut microbial homeostasis, and protect against multi-organ injury in septic models. Notably, EONPs enhance the production of the microbiota-derived metabolite 5-hydroxyindoleacetic acid (5-HIAA), which is functionally linked to the anti-inflammatory response and may further support macrophage reprogramming. Our findings establish a previously unrecognized strategy for precise metabolic and microbiota-driven modulation of macrophages, offering a conceptual framework for further investigation of macrophage-targeted nanotherapeutics in sepsis.
Indexed as
Identifiers
What OpenQuestion holds
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.