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Plaque vulnerability has been the subject of several recent studies aimed at reducing the risk of stroke and carotid artery stenosis. Atherosclerotic plaque development is a complex process involving inflammation mediated by macrophages. Plaques become more vulnerable when the equilibrium between macrophage recruitment and clearance is disturbed. Lipoperoxides, which are affected by iron levels in cells, are responsible for the cell death seen in ferroptosis. Ferroptosis results from lipoperoxide-induced mitochondrial membrane toxicity. Atherosclerosis in ApoE(−/−) mice is reduced when ferroptosis is inhibited and iron intake is limited. Single-cell sequencing revealed that a ferroptosis-related gene was substantially expressed in atherosclerosis-modeled macrophages. Since ferroptosis can be regulated, it offers hope as a non-invasive method of treating carotid plaque. In this study, we discuss the role of ferroptosis in atherosclerotic plaque vulnerability, including its mechanism, regulation, and potential future research directions.

Although carbon dots (CDs) have been widely investigated as the fluorescence material, research on room temperature phosphorescence (RTP) CDs is still limited. In this work, diethylenetriaminepentaacetic acid (DTPA) was employed as the raw material to synthesize carbon quantum dots (denoted as CQDs-1) by a hydrothermal method. The resulting CQDs-1 inherited CO groups and N atoms from DTPA, which promoted the formation of triplet excitons under light excitation. On this basis, the CQDs-1 were dispersed in a poly-(vinyl alcohol) (PVA) matrix to prepare CQDs-1-PVA composites that exhibited an optimal emission peak at ∼466 nm and emitted the visible afterglow lasting for 8 s. Moreover, tartaric acid (TA) was combined with DTPA as the raw material to synthesize CQDs-2, which induced the formation of π–π conjugated areas in CQDs. As a result, the emission wavelength was slightly red-shifted, and the duration time of afterglow of the CQDs-2-PVA composite was increased to 9 s. Due to the ultralong-lifetime RTP properties of the CQDs-based composites, their applications in the fields of information encryption and anticounterfeiting have also been investigated. Overall, our work offered a convenient avenue for the synthesis of high-quality RTP CQDs. [ABSTRACT FROM AUTHOR]

Opioids introduced at reperfusion (R) following ischemia (I) reduce infarct size much like postconditioning, suggesting the hypothesis that postconditioning increases cardiac opioids and activates local opioid receptors. Anesthetized male rats subjected to 30 rain regional I and 3 h R were postconditioned with three cycles of 10 s R and 10 s reocclusion at onset of R. Naloxone (NL), its peripherally restricted analog naloxone methiodide, [delta]-opioid receptor (DOR) antagonist naltrindole (NTI), [kappa]-opioid receptor antagonist norbinaltorphimine (NorBNI), and [mu]-opioid receptor (MOR) antagonist H-D-Phe-CysTyr-D-Trp-Arg-Thr-Pen-Thr-[NH.sup.2] (CTAP) were administered intravenously 5 rain before R. The area at risk (AAR) was comparable among groups, and postconditioning reduced infarct size from 57 [+ or -] 2 to 42 [+ or -] 2% (P < 0.05). None of the antagonists alone altered infarct size. All antagonists abrogated postconditioning protection at higher doses. However, blockade of infarct sparing by postconditioning was lost, since tested doses of NL, NTI, NorBNI, and CTAP were lowered. The efficacy of NorBNI declined first at 3.4 [micro]mol/kg, followed sequentially by NTI (1.1), NL (0.37), and CTAP (0.09), suggesting likely MOR and perhaps DOR participation. Representative small, intermediate, and large enkephalins in the AAR were quantified (fmol/mg protein; mean [+ or -] SE). I/R reduced proenkephalin (58 [+ or -] 9 vs. 33 [+ or -] 4; P < 0.05) and sum total of measured enkephalins, including proenkephalin, peptide B, methionine-enkephalin, and methionine-enkephalin-arginine-phenylalanine (139 [+ or -] 17 vs. 104 [+ or -] 7; P < 0.05) compared with shams. Postconditioning increased total enkephalins (89 [+ or -] 8 vs. 135 [+ or -] 5; P < 0.05) largely by increasing proenkephalin (33 [+ or -] 4 vs. 96 [+ or -] 7; P < 0.05). Thus the infarct-sparing effect of postconditioning appeared to involve endogenously activated MORs and possibly DORs, and preservation of enkephalin precursor synthesis in the AAR. postconditioning; reperfusion injury; opioid receptor activation; myocardial enkephalins

Protease-activated receptor-2 (PAR-2) may have proinflammatory effects in some tissues and protective effects in other tissues. The role of PAR-2 in in vivo myocardial ischemia-reperfusion has not yet been determined. This study tested the hypothesis that PAR-2 activation with the PAR-2 agonist peptide SLIGRL (PAR-2 AP) reduces myocardial infarct size when given at reperfusion in vivo, and this cardioprotection involves the ERK1/2 pathway. Anesthetized rats were randomly assigned to the following groups with 30 min of regional ischemia and 3 h reperfusion: 1) control with saline; 2) vehicle (DMSO); 3) PAR-2 AP, 1 mg/kg given intravenously 5 min before reperfusion; 4) scrambled peptide (SP), 1 mg/kg; 5) the ERK1/2 inhibitor PD-98059 (PD), 0.3 mg/kg given l0 min before reperfusion; 6) the phosphatidylinositol 3-kinase inhibitor LY-294002 (LY), 0.3 mg/kg given 10 min before reperfusion; 7) PD + PAR-2 AP, 0.3 mg/kg PD given 5 min before PAR-2 AP; 8) LY + PAR-2 AP, 0.3 mg/kg LY given 5 min before PAR-2 AP; 9) chelerythrine (Chel) alone, 5 mg/kg given 10 min before reperfusion; and 10) Chel + PAR-2 AP, Chel was given 5 min before PAR-2 AP (10 min before reperfusion). Activation of ERKI/2, ERK5, Akt, and the downstream targets of ERK1/2 [P90 RSK and bcl-xl/bcl-2-associated death promoter (BAD)] was determined by Western blot analysis in separate experiments. PAR-2 AP significantly reduced infarct size compared with control (36 [+ or -] 2% vs. 53 [+ or -] 1%, P < 0.05), and SP had no effect on infarct size (53 [+ or -] 3%). PAR-2 AP significantly increased phosphorylation of ERK1/2, p90RSK, and BAD but not Akt or ERK5. Accordingly, the infarct-size sparing effect of PAR-2 AP was abolished by PD (PAR-2 AP, 36 [+ or -] 2% vs. PD + PAR-2 AP, 50 [+ or -] 1%; P < 0.05) and by Chel (Chel + PAR-2 AP, 58 [+ or -] 2%) but not by LY (PAR-2 AP, 36 [+ or -] 2% vs. LY + PAR-2 AP, 38 [+ or -] 3%; P > 0.05). Therefore, PAR-2 activation is cardioprotective in the in vivo rat heart ischemia-reperfusion model, and this protection involves the ERK1/2 pathway and PKC. reperfusion injury; infarct size; protein kinases

We have shown that intermittent interruption of immediate reflow at reperfusion (i.e., postconditioning) reduces infarct size in in vivo models after ischemia. Cardioprotection of postconditioning has been associated with attenuation of neutrophil-related events. However, it is unknown whether postconditioning before reoxygenation after hypoxia in cultured cardiomyocytes in the absence of neutrophils confers protection. This study tested the hypothesis that prevention of cardiomyocyte damage by hypoxic postconditioning (Postcon) is associated with a reduction in the generation of reactive oxygen species (ROS) and intracellular [Ca.sup.2+] overload. Primary cultured neonatal rat cardiomyocytes were exposed to 3 h of hypoxia followed by 6 h of reoxygenation. Cardiomyocytes were postconditioned after the 3-h index hypoxia by three cycles of 5 min of reoxygenation and 5 rain of rehypoxia applied before 6 h of reoxygenation. Relative to sham control and hypoxia alone, the generation of ROS (increased lucigenin-enhanced chemiluminescence, SOD-inhibitable cytochrome c reduction, and generation of hydrogen peroxide) was significantly augmented after immediate reoxygenation as was the production of malondialdehyde, a product of lipid peroxidation. Concomitant with these changes, intracellular and mitochondrial [Ca.sup.2+] concentrations, which were detected by fluorescent fluo-4 AM and Xrhod-1 AM staining, respectively, were elevated. Cell viability assessed by propidium iodide staining was decreased consistent with increased levels of lactate dehydrogenase after reoxygenation. Postcon treatment at the onset of reoxygenation reduced ROS generation and malondialdehyde concentration in media and attenuated cardiomyocyte death assessed by propidium iodide and lactate dehydrogenase. Postcon treatment was associated with a decrease in intracellular and mitochondrial [Ca.sup.2+] concentrations. These data suggest that Postcon treatment reduces reoxygenation-induced injury in cardiomyocytes and is potentially mediated by attenuation of ROS generation, lipid peroxidation, and intracellular and mitochondrial [Ca.sup.2+] overload. reactive oxygen species; hypoxia; reoxygenation; superoxide; ischemia; reperfusion