Background— Although preclinical data suggested that tumor necrosis factor-α (TNF) neutralization in heart failure (HF) would be beneficial, clinical trials of TNF antagonists were paradoxically ...negative. We hypothesized that TNF induces opposing inflammatory and remodeling responses in HF that are TNF-receptor (TNFR) specific. Methods and Results— HF was induced in wild-type (WT), TNFR1 −/− , and TNFR2 −/− mice via coronary ligation. Compared with WT HF, 4-week postinfarction survival was significantly improved in both TNFR1 −/− and TNFR2 −/− HF. Compared with sham, WT HF hearts exhibited significant remodeling with robust activation of nuclear factor (NF)-κB, p38 mitogen-activated protein kinase, and JNK2 and upregulation of TNF, interleukin (IL)-1β, IL-6, and IL-10. Compared with WT HF, TNFR1 −/− HF exhibited (1) improved remodeling, hypertrophy, and contractile function; (2) less apoptosis; and (3) diminished NF-κB, p38 mitogen-activated protein kinase, and JNK2 activation and cytokine expression. In contrast, TNFR2 −/− HF showed exaggerated remodeling and hypertrophy, increased border zone fibrosis, augmented NF-κB and p38 mitogen-activated protein kinase activation, higher IL-1β and IL-6 gene expression, greater activated macrophages, and greater apoptosis. Oxidative stress and diastolic function were improved in both TNFR1 −/− and TNFR2 −/− HF. In H9c2 cardiomyocytes, sustained NF-κB activation was proapoptotic, an effect dependent on TNFR1 signaling, whereas TNFR2 overexpression attenuated TNF-induced NF-κB activation. Conclusions— TNFR1 and TNFR2 have disparate and opposing effects on remodeling, hypertrophy, NF-κB, inflammation, and apoptosis in HF: TNFR1 exacerbates, whereas TNFR2 ameliorates, these events. However, signaling through both receptors is required to induce diastolic dysfunction and oxidative stress. TNFR-specific effects in HF should be considered when therapeutic anti-TNF strategies are developed.
Heme oxygenase-1 (HO-1) is an inducible stress-response protein that imparts antioxidant and antiapoptotic effects. However, its pathophysiological role in cardiac remodeling and chronic heart ...failure (HF) is unknown. We hypothesized that induction of HO-1 in HF alleviates pathological remodeling.
Adult male nontransgenic and myocyte-restricted HO-1 transgenic mice underwent either sham operation or coronary ligation to induce HF. Four weeks after ligation, nontransgenic HF mice exhibited postinfarction left ventricular (LV) remodeling and dysfunction, hypertrophy, fibrosis, oxidative stress, apoptosis, and reduced capillary density, associated with a 2-fold increase in HO-1 expression in noninfarcted myocardium. Compared with nontransgenic mice, HO-1 transgenic HF mice exhibited significantly (P<0.05) improved postinfarction survival (94% versus 57%) and less LV dilatation (end-diastolic volume, 46+/-8 versus 85+/-32 microL), mechanical dysfunction (ejection fraction, 65+/-9% versus 49+/-16%), hypertrophy (LV/tibia length 4.4+/-0.4 versus 5.2+/-0.6 mg/mm), interstitial fibrosis (11.2+/-3.1% versus 18.5+/-3.5%), and oxidative stress (3-fold reduction in tissue malondialdehyde). Moreover, myocyte-specific HO-1 overexpression in HF promoted tissue neovascularization and ameliorated myocardial p53 expression (2-fold reduction) and apoptosis. In isolated mitochondria, mitochondrial permeability transition was inhibited by HO-1 in a carbon monoxide (CO)-dependent manner and was recapitulated by the CO donor tricarbonylchloro(glycinato)ruthenium(II) (CORM-3). HO-1-derived CO also prevented H2O2-induced cardiomyocyte apoptosis and cell death. Finally, in vivo treatment with CORM-3 alleviated postinfarction LV remodeling, p53 expression, and apoptosis.
HO-1 induction in the failing heart is an important cardioprotective adaptation that opposes pathological LV remodeling, and this effect is mediated, at least in part, by CO-dependent inhibition of mitochondrial permeability transition and apoptosis. Augmentation of HO-1 or its product, CO, may represent a novel therapeutic strategy for ameliorating HF.
In this paper, we investigate the blow up criteria for the local smooth solutions to the three-dimensional incompressible Navier-Stokes-Landau-Lifshitz system via the components of the velocity field ...u or velocity gradient ∇u and the gradient orientation field ∇d. More precisely, the first result is the Serrin-type blow up criterion with the components of u and ∇d. The remaining is relevant to ∇u and ∇d corresponding to the Besov space with negative index. As corollaries, the blow up criteria in both of the Besov space with negative index and BMO space with reference to u and ∇d are obtained.
The self-healing microcapsules can be buried in the coating to improve the anticorrosive ability. In this paper, self-healing microcapsules of polyurea (PU)/melamine resin (MF) double shell were ...prepared by in-situ polymerization and interfacial polymerization with isocyanate as the core material. Scanning electron microscope was used to observe the microcapsule morphology. The structures of microcapsules prepared with different chain extenders were characterized by Fourier transform infrared spectroscopy. The micromanipulation system was used to loading–holding, loading–unloading and loading to rupture individual microcapsules, so as to explore the mechanical properties of microcapsules. The Young's modulus corresponding to microcapsules was calculated by mathematical model fitting. The self-healing properties of microcapsule coating were characterized by optical microscope. The experimental results showed that the microcapsule shell prepared under optimized conditions had a complete morphology and good mechanical properties. The microcapsule was in the elastic deformation stage under small deformation, and the plastic deformation stage under large deformation. The Young's modulus range of microcapsules was 9.29–14.51 MPa, and the corresponding Young's modulus could be prepared by adjusting the process. The surface crack of the coating containing microcapsule could heal itself after 48 h in a humid environment.
PU/MF double-shell microcapsule was prepared successfully and its self-healing behaviors were detected with SEM. The factors influencing the mechanical properties of microcapsules have been revealed. Display omitted
Diabetic cardiomyopathy is related directly to hyperglycemia. Cell death such as apoptosis plays a critical role in cardiac pathogenesis. Whether hyperglycemia induces myocardial apoptosis, leading ...to diabetic cardiomyopathy, remains unclear. We tested the hypothesis that apoptotic cell death occurs in the diabetic myocardium through mitochondrial cytochrome c-mediated caspase-3 activation pathway. Diabetic mice produced by streptozotocin and H9c2 cardiac myoblast cells exposed to high levels of glucose were used. In the hearts of diabetic mice, apoptotic cell death occurred as detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Correspondingly, caspase-3 activation as determined by enzymatic assay and mitochondrial cytochrome c release detected by Western blotting analysis were observed. Supplementation of insulin inhibited diabetes-induced myocardial apoptosis as well as suppressed hyperglycemia. To explore whether apoptosis in diabetic hearts is related directly to hyperglycemia, we exposed cardiac myoblast H9c2 cells to high levels of glucose (22 and 33 mmol/l) in cultures. Apoptotic cell death was detected by TUNEL assay and DAPI nuclear staining. Caspase-3 activation with a concomitant mitochondrial cytochrome c release was also observed. Apoptosis or activation of caspase-3 was not observed in the cultures exposed to the same concentrations of mannitol. Inhibition of caspase-3 with a specific inhibitor, Ac-DEVD-cmk, suppressed apoptosis induced by high levels of glucose. In addition, reactive oxygen species (ROS) generation was detected in the cells exposed to high levels of glucose. These results suggest that hyperglycemia directly induces apoptotic cell death in the myocardium in vivo. Hyperglycemia-induced myocardial apoptosis is mediated, at least in part, by activation of the cytochrome c-activated caspase-3 pathway, which may be triggered by ROS derived from high levels of glucose.
In this paper, we will research the regularity of the strong solution to the Landau–Lifshitz–Gilbert equation. We obtain a blowup criterion of the strong solution to the Landau–Lifshitz–Gilbert ...equation in a multi-dimensional bounded domain with Neumann boundary condition.
In this paper, we establish a new blow-up criterion of the strong solution to the quantum hydrodynamic model. This blow-up criterion is different from the one established in our former paper (Wang ...and Guo, 2020). This blow-up criterion only depends on the gradient of the velocity, but also the first order time derivative of the square root of the density.
PDF
