Notopterol is a naturally occurring furanocoumarin compound found in the root of Notopterygium incisum. Hyperuricemia involves the activation of chronic inflammation and leads to cardiac damage. Whether notopterol has cardioprotective potential in hyperuricemia mice remains elusive. The hyperuricemic mouse model was constructed by administration of potassium oxonate and adenine every other day for six weeks. Notopterol (20 mg/kg) and allopurinol (10 mg/kg) were given daily as treatment, respectively. The results showed that hyperuricemia dampened heart function and reduced exercise capacity. Notopterol treatment improved exercise capacity and alleviated cardiac dysfunction in hyperuricemic mice. P2X7R and pyroptosis signals were activated both in hyperuricemic mice and in uric acid-stimulated H9c2 cells. Additionally, it was verified that inhibition of P2X7R alleviated pyroptosis and inflammatory signals in uric acid-treated H9c2 cells. Notopterol administration significantly suppressed expression levels of pyroptosis associated proteins and P2X7R in vivo and in vitro. P2X7R overexpression abolished the inhibition effect of notopterol on pyroptosis. Collectively, our findings suggested that P2X7R played a critical role in uric acid-induced NLRP3 inflammatory signals. Notopterol inhibited pyroptosis via inhibiting the P2X7R/NLRP3 signaling pathway under uric acid stimulation. Notopterol might represent a potential therapeutic strategy against pyroptosis and improve cardiac function in hyperuricemic mice.

(1) Background: Despite the evidence that ferroptosis is involved in myocardial ischemia-reperfusion (MIR), the critical regulator of ferroptosis in MIR remains unclear. (2) Methods: We included three GEO datasets and a set of ferroptosis-related genes with 259 genes. Following the identification of the differentially expressed ferroptosis-related genes (DEFRGs) and hub genes, we performed the functional annotation, protein–protein interaction network, and immune infiltration analysis. The GSE168610 dataset, a cell model, and an animal model were then used to verify key genes. (3) Results: We identified 17 DEFRGs and 9 hub genes in the MIR samples compared to the control. Heme oxygenase 1 (Hmox1), activating transcription factor 3 (Atf3), epidermal growth factor receptor (Egfr), and X-box binding protein 1 (Xbp1) were significantly upregulated in response to ischemic and hypoxic stimuli. In contrast, glutathione peroxidase 4 (Gpx4) and vascular endothelial growth factor A (Vegfa) were consistently decreased in either the oxygen and glucose deprivation/reoxygenation cell or the MIR mouse model. (4) Conclusions: This study emphasized the relevance of ferroptosis in MIR. It has been successfully demonstrated that nine ferroptosis-related genes (Hmox1, Atf3, Egfr, Gpx4, Cd44, Vegfa, asparagine synthetase (Asns), Xbp1, and bromodomain containing 4 (Brd4)) are involved in the process. Additional studies are needed to explore potential therapeutic targets for MIR.

To observe the influence of remote ischemic preconditioning (R-IPC) and remote ischemic perconditioning (R-IPER) on the lower limbs of rabbits with lung allograft ischemia-reperfusion injury (IRI). Sixty rabbits were randomly divided into one of four groups: control (C), classic ischemic preconditioning (C-IPC), R-IPC, and R-IPER. The allogeneic lung transplantation model was established in rabbits, and the protective effects of R-IPC and R-IPER on transplanted lungs were determined and compared to classic ischemic preconditioning (C-IPC) IRI. Changes in blood oxygen were measured in each group before and after transplantation. After transplantation, levels of serum malondialdehyde (MDA), superoxide dismutase (SOD), and tumor necrosis factor-α (TNF-α), lung wet/dry weight ratio, as well as quantitative and organizational differences in the lungs were analyzed. After reperfusion, blood oxygen values in the R-IPC group and C-IPC groups were higher than in the C and R-IPER groups at 60 minutes and 120 minutes after transplantation (p < 0.05). Serum SOD content in the R-IPC and C-IPC groups was higher than in the C and R-IPER groups (p < 0.05) after reperfusion. Serum MDA, TNF-α level, and lung wet/dry weight ratio and quantitative measurements of histological damage were lower in the R-IPC and the C-IPC groups than those in the C and R-IPER groups (p < 0.05). No statistically significant differences were observed between the L-IP and the C-IP groups or between the R-IPER and the C groups. Classic preconditioning and remote preconditioning of rabbit lung allograft IRI had similar protective effects. The lower limb ischemia with the remote processing method used in this experiment did not produce a protective effect for lung allograft IRI.

Time‐restricted feeding (TRF) restricts food intake to daily windows, yet its efficacy against vascular aging and underlying mechanisms remain unclear. Here, we demonstrate that TRF attenuates angiotension II ‐induced accelerated vascular aging by reshaping gut microbiota, stabilizing microbial diversity, and elevating the Firmicutes/Bacteroidetes ratio. TRF preserved intestinal barrier integrity, upregulated tight junction proteins (Occludin, ZO‐1, MUC2), reduced serum lipopolysaccharide, and suppressed systemic inflammation. These benefits translated into alleviated hypertension, aortic stiffness (reflected by pulse wave velocity), and pathological cardiac remodeling. Fecal microbiota transplantation recapitulated these effects, whereas antibiotic‐induced microbiota depletion abolished TRF protection; importantly, exogenous acetate supplementation fully restored the phenotypes, establishing acetic acid as the critical downstream mediator. Mechanistically, acetic acid bound to GPR43, inhibited HDAC3, increased H4K8ac acetylation, blocked NLRP3‐mediated pyroptosis, and reduced senescence markers (p53, p21, p16) in human umbilical vein endothelial cells, aorta, and heart. 16S rRNA sequencing and short ‐ chain fatty acids metabolomic profiling further identified Limosilactobacillus as the primary acetic acid‐producing bacterium enriched by TRF. Together, we uncover a Limosilactobacillus ‐acetic acid‐GPR43/HDAC3/H4K8ac/NLRP3 axis, offering mechanistic insights into TRF as a non‐pharmacological strategy against age‐related cardiovascular diseases.