Cure8 research brief
Patients on or considering infliximab may be interested because the paper identifies a possible molecular reason some people don’t respond and tests strategies that could, in principle, improve response to infliximab.
Patients with ulcerative colitis who are non-responders or on anti-TNF therapy; gastroenterologists and IBD researchers studying biologic resistance or new adjunctive treatments; translational scientists exploring immune targets like PTGS2/COX-2.
This study analyzed human colonic RNA-sequencing and single-cell data to identify molecular drivers of primary non-response (PNR) to infliximab in ulcerative colitis.
The authors report that PTGS2 (COX-2) expression in CD14+S100A9+ inflammatory monocytes correlated with neutrophil recruitment and PNR, and that virtual knockout and cell experiments implicate NF-κB/CXCL8 signaling in this process.
They used network pharmacology and molecular docking to nominate components of the traditional herbal formula Gegen Qinlian Decoction (GQD)—notably quercetin—as potential PTGS2 inhibitors.
In cell assays quercetin reduced LPS-induced PTGS2 and downstream signaling; in a DSS mouse colitis model, GQD lowered colonic PTGS2 and neutrophil accumulation and improved response to infliximab. This report is presented as an abstract/summary of mechanistic human data, in vitro validation, and a mouse therapeutic experiment.
It suggests monocyte-derived PTGS2 as a potential target to overcome infliximab PNR and proposes GQD/quercetin as candidate modulators, but these findings are preclinical and hypothesis-generating.
This article integrates human sequencing analyses, cell experiments, and a mouse colitis model. The therapeutic data for Gegen Qinlian Decoction/quercetin are preclinical; this is not evidence that these treatments are safe or effective in people with UC. Further clinical studies would be required before changing care.
Review the original publication for the complete reporting, methods, and context.
Funding disclosed by the source: National Natural Science Foundation of China, award 82360115, 82160111, 825B2014
This Cure8 brief is based on source text from the linked article. Cure8 is informational only and is not a substitute for professional medical advice, diagnosis, or treatment.
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