This study revealed that exosomes derived from M2 macrophages inhibited podocyte pyroptosis via transferring AFAP1-AS1 to podocytes. Mechanistically, AFAP1-AS1 interacted with EZH2 to transcriptionally regulate H3K27me3 level in the NLRP3 promoter region, thus epigenetically repressing NLRP3 expression to inhibit podocyte pyroptosis. Our findings provided a potential molecular target for the therapeutic interventions of diabetic nephropathy.

Graphical summary of the study: CS, citrate synthase; DRP1, dynamin-related protein 1; FIS1, fission 1; SP, short photoperiod; LP, long photoperiod; MFF, mitochondrial fission factor.

GPR39 activation by TC-G 1008 attenuates AngII-induced AAA in ApoE−/− mice by reducing oxidative stress (lowering MDA, increasing SOD/GSH) and suppressing VEGF-A/VEGFR2 signalling. The protective mechanism involves downregulation of the transcription factor ETS-1, which mediates VEGF-A/VEGFR2 expression and angiogenic tube formation in HUVECs. ETS-1 overexpression reverses TC-G 1008's effects, confirming its pivotal role in GPR39-mediated protection against AAA.

This schematic workflow demonstrates the neuroprotective potential of isoxazolone derivatives by a series of studies starting from target identification to simulation, followed by in vitro and in vivo analysis, including behavioral, biochemical, and morphological studies.

LIN interacted with COX2 to inhibit inflammation, apoptosis and oxidative stress in LPS-induced AKI.