Growth differentiation factor 11 ameliorates experimental colitis by inhibiting NLRP3 inflammasome activation.

Growth differentiation factor 11 (GDF11) has an anti-inflammatory effect in the mouse model of atherosclerosis and Alzheimer's disease, but how GDF11 regulates intestinal inflammation during ulcerative colitis (UC) is poorly defined. The Nod-like receptor family pyrin domain-1 containing 3 (NLRP3) inflammasome is closely associated with intestinal inflammation because of its ability to increase IL-1ß secretion. Our aim is to determine whether GDF11 has an effect on attenuating experimental colitis in mice. In this study, using a dextran sodium sulfate (DSS)-induced acute colitis mouse model, we reported that GDF11 treatment attenuated loss of body weight, the severity of the disease activity index, shortening of the colon, and histological changes in the colon. GDF11 remarkably suppressed IL-1ß secretion and NLRP3 inflammasome activation in colon samples and RAW 264.7 cells, such as the levels of NLRP3 and activated caspase-1. Furthermore, we found that GDF11 inhibited NLRP3 inflammasome activation by downregulating the Toll-like receptor 4/NF-κB p65 pathway and reactive oxygen species production via the typical Smad2/3 pathway. Thus, our research shows that GDF11 alleviates DSS-induced colitis by inhibiting NLRP3 inflammasome activation, providing some basis for its potential use in the treatment of UC. NEW & NOTEWORTHY Here, we identify a new role for growth differentiation factor 11 (GDF11), which ameliorates dextran sodium sulfate-induced acute colitis. Meanwhile, we discover a new phenomenon of GDF11 inhibiting IL-1ß secretion and Nod-like receptor family pyrin domain-1 containing 3 (NLRP3) inflammasome activation. These findings reveal that GDF11 is a new potential candidate for the treatment of ulcerative colitis patients with a hyperactive NLRP3 inflammasome.

Development of a Point-of-Care Test Based on Selenium Nanoparticles for Heart-Type Fatty Acid-Binding Proteins in Human Plasma and Blood.

Purpose: A rapid, convenient, cost-effective in-home test method for identifying heart-type fatty acid-binding protein (H-FABP) in plasma and blood by a lateral-flow immunoassay (LFIA) based on selenium nanoparticles (SeNPs) was developed. Methods: SeNPs were synthesized by using L-ascorbic acid to reduce seleninic acid at room temperature and conjugated with an anti-H-FABP monoclonal antibody. The limit of detection, specificity, and stability were measured, and clinical samples were analyzed. Results: The SeNPs were spherical with a diameter of 39.48 ± 3.72 nm and were conjugated successfully with an anti-H-FABP antibody, resulting in a total diameter of 46.52 ± 2.95 nm. The kit was designed for the determination of H-FABP in plasma specimens and whole blood specimens. The limit of detection was 1 ng/mL in plasma and blood, and the results could be determined within 10 min. No cross-reaction occurred with cardiac troponin I, creatine kinase-MB or myoglobin. The kits were stored at 40 °C for up to 30 days without significant loss of activity. The sensitivity was determined to be 100%, the specificity 96.67%, and the overall coincidence rate 97.83%. Conclusion: This SeNP assay kit can conveniently, rapidly, and sensitively detect H-FABP in plasma or blood with a readout of a simple color change visible to the naked eye with no special device, and can be used as an auxiliary means for the early screening of AMI. Clinical Trial Registration: Plasma and blood samples were used under approval from the Experimental Animal Ethics committee of the Joint National Laboratory for Antibody Drug Engineering, Henan University. The clinical trial registration number was HUSOM-2019-047.