Myocardial infarction (MI) is a leading cause of death worldwide for which there is no cure. Although cardiac cell death is a well-recognized pathological mechanism of MI, therapeutic blockade of cell death to treat MI is not straightforward. Death receptor 5 (DR5) and its ligand TRAIL [tumor necrosis factor (TNF)–related apoptosis-inducing ligand] are up-regulated in MI, but their roles in pathological remodeling are unknown. Here, we report that blocking TRAIL with a soluble DR5 immunoglobulin fusion protein diminished MI by preventing cardiac cell death and inflammation in rats, pigs, and monkeys. Mechanistically, TRAIL induced the death of cardiomyocytes and recruited and activated leukocytes, directly and indirectly causing cardiac injury. Transcriptome profiling revealed increased expression of inflammatory cytokines in infarcted heart tissue, which was markedly reduced by TRAIL blockade. Together, our findings indicate that TRAIL mediates MI directly by targeting cardiomyocytes and indirectly by affecting myeloid cells, supporting TRAIL blockade as a potential therapeutic strategy for treating MI.

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 NLRP3 (Nod-like receptor family pyrin domain-1 containing 3) inflammasome is closely associated with intestinal inflammation due to its ability to increase IL-1β secretion. Our aim is to determine whether GDF11 has an effect on attenuating experimental colitis in mice. In this study, using a dextran sulfate sodium (DSS)-induced acute colitis mouse model, we reported that GDF11 treatment attenuated loss of body weight, the severity of the disease activity index (DAI), shortening of the colon, and histological changes in the colon. GDF11 remarkably suppressed IL-1β secretion and NLRP3 inflammasome activation in colon samples and RAW264.7 cells, such as the levels of NLRP3 and activated caspase-1. Furthermore, we found that GDF11 inhibited NLRP3 inflammasome activation by downregulating the TLR4/NF-κB p65 pathway and reactive oxygen species (ROS) 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.

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The objective of this study was to develop aquatic collagen production from fish processing by-product skin as a possible alternative to terrestrial sources. Silver carp skin collagen (SCSC) was isolated and identified as type I collagen, and LC-MS/MS analysis confirmed the SCSC as Hypophthalmichthys molitrix type I collagen, where the yield of SCSC was 40.35 ± 0.63% (dry basis weight). The thermal denaturation temperature (Td) value of SCSC was 30.37 °C, which was superior to the collagen of deep-sea fish and freshwater fish. Notably, SCSC had higher thermal stability than human placental collagen, and the rheological experiments showed that the SCSC was a shear-thinning pseudoplastic fluid. Moreover, SCSC was functionally superior to some other collagens from terrestrial sources, such as sheep, chicken cartilage, and pig skin collagen. Additionally, SCSC could provide a suitable environment for MC3T3-E1 cell growth and maintain normal cellular morphology. These results indicated that SCSC could be used for further applications in food, cosmetics, and biomedical fields.