Context: Curcumin has long been used as a condiment and a traditional medicine worldwide.Objective: The current study investigates the possible protective effect of curcumin on heart function in myocardium ischemia-reperfusion (MIR) rats.Materials and methods: We fed Sprague–Dawley (SD) rats (10 in each group) either curcumin (10, 20 or 30 mg/kg/d) or saline. Twenty days later, the rats were subjected to myocardial injuries by ligating the left anterior descending coronary artery (60 min), and subsequently, the heart (3 h) reperfused by releasing the ligation. Then, lipid profile, lipid peroxidation products, antioxidant enzymes and gene expression were assessed in myocardium tissue.Results: Only the rats that were supplemented with curcumin (10, 20 or 30 mg/kg/d) showed significant (p < 0.05) reductions in oxidative stress (3-fold), infarct size (2.5-fold), which was smaller than that of the control group. The percentage of infarct size in MIR rats with curcumin at 10, 20 or 30 mg/kg/d decreased (from 49.1% to 18.3%) compared to ischemia-reperfusion (I/R). The enhanced phosphorylation of STAT3 was further strengthened by curcumin (10, 20 or 30 mg/kg/d) in a dose-dependent manner.Discussion and conclusion: Curcumin intake might reduce the risk of coronary heart disease by stimulating JAK2/STAT3 signal pathway, decreasing oxidative damage and inhibiting myocardium apoptosis.
SENCR is a human-specific, vascular cell-enriched long-noncoding RNA (lncRNA) that regulates vascular smooth muscle cell and endothelial cell (EC) phenotypes. The underlying mechanisms of action of SENCR in these and other cell types is unknown. Here, levels of SENCR RNA are shown to be elevated in several differentiated human EC lineages subjected to laminar shear stress. Increases in SENCR RNA are also observed in the laminar shear stress region of the adult aorta of humanized SENCR-expressing mice, but not in disturbed shear stress regions. SENCR loss-of-function studies disclose perturbations in EC membrane integrity resulting in increased EC permeability. Biotinylated RNA pull-down and mass spectrometry establish an abundant SENCR-binding protein, cytoskeletal-associated protein 4 (CKAP4); this ribonucleoprotein complex was further confirmed in an RNA immunoprecipitation experiment using an antibody to CKAP4. Structure–function studies demonstrate a noncanonical RNA-binding domain in CKAP4 that binds SENCR. Upon SENCR knockdown, increasing levels of CKAP4 protein are detected in the EC surface fraction. Furthermore, an interaction between CKAP4 and CDH5 is enhanced in SENCR-depleted EC. This heightened association appears to destabilize the CDH5/CTNND1 complex and augment CDH5 internalization, resulting in impaired adherens junctions. These findings support SENCR as a flow-responsive lncRNA that promotes EC adherens junction integrity through physical association with CKAP4, thereby stabilizing cell membrane-bound CDH5.
An accurate density-functional method is used to study systematically half-metallic ferromagnetism and stability of zincblende phases of 3d-transition-metal chalcogenides. The zincblende CrTe, CrSe, and VTe phases are found to be excellent half-metallic ferromagnets with large halfmetallic gaps (up to 0.88 eV). They are mechanically stable and approximately 0.31-0.53 eV per formula unit higher in total energy than the corresponding nickel-arsenide ground-state phases, and therefore would be grown epitaxially in the form of films and layers thick enough for spintronic applications.PACS numbers: 75.90.+w, 62.25.+g, 73.22.-f, 75.30.-m Phys Rev Lett 91, 037204 (2003) Half-metallic ferromagnets are seen as a key ingredient in future high performance spintronic devices, because they have only one electronic spin channel at the Fermi energy and, therefore, may show nearly 100 % spin polarization [1,2]. Since de Groot et al's discovery [3] in 1983, a lot of half-metallic ferromagnets have been theoretically predicted and some of them furthermore have been confirmed experimentally [4,5,6,7]. Much attention has been paid to understanding the mechanism behind the half-metallic magnetism and to studying its implication on various physical properties [8,9]. However, it is highly desirable to explore new halfmetallic ferromagnetic materials which are compatible with important III-V and II-VI semiconductors. For this purpose, effort has be made on the metastable zincblende (B3) phases such as the transition-metal pnictides [10,11,12,13,14,15,16,17,18,19,20]. Although zincblende phases of MnAs [11], CrAs [12,13] and CrSb [14] have been successfully fabricated as nanodots, ultrathin films and ultrathin layers in multilayers, it has not been possible to grow the zincblende half-metallic ferromagnetic phases as high-quality layers or thick films. This is due to the metastable zincblende phases being about 1 eV per formula unit higher in energy than the ground state nickel-arsenide (B8 1 ) phases. However, spintronic devices require thick films or layers. Therefore, it is important to explore theoretically other halfmetallic ferromagnetic materials, which on the one hand are compatible with the binary tetrahedral-coordinated semiconductors, and on the other hand are not only low in energy with respect to the corresponding ground-state structures but also mechanically stable against structural deformations.In this Letter we make use of an accurate fullpotential density-functional method to study systematically transition-metal chalcogenides in the zincblende and nickel-arsenide structures in order to find halfmetallic ferromagnetic phases which could be realized in the form of films and layers thick enough. We shall show that CrTe, CrSe, and VTe in the zincblende structure are excellent half-metallic ferromagnets with wide halfmetallic gaps. They will be proved to be mechanically stable and approximately 0.31-0.53 eV per formula unit higher in energy than the corresponding ground-state phases, and therefore would be grown epitax...
A hot filament chemical vapor deposition ͑HFCVD͒ method has been used to investigate the effects of atomic hydrogen and active carbon species on the growth of 1 mm vertically aligned single-walled carbon nanotubes ͑VA-SWNTs͒. Isotopic shifts of the tangential phonon mode of SWNTs indicate that SWNT growth occurs primarily via reactions of acetylene and ethylene. The authors find that the presence of atomic hydrogen and active carbon species such as ethylene and acetylene appears to be essential for both nucleation and growth of VA-SWNTs in this HFCVD.
The full-potential augmented plane wave plus local orbital method within density-functional theory is used to predict that MnBi in the zinc-blende structure is a true half-metallic ferromagnet with a magnetic moment of 4.000 B per formula unit. This contrasts with the zinc-blende phase of MnAs, which is only a nearly half-metallic ferromagnet. This half-metallic ferromagnetic behavior of zinc-blende MnBi is found to be robust against compressive volume changes of up to 15%, its stability being enhanced by the relativistic shift of the valence s state energy levels. Zinc-blende MnBi could possibly be grown epitaxially on the important binary semiconductors such as InSb or CdTe, although it remains to be seen whether epitaxially it retains its halfmetallic ferromagnetic state.
Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) are a promising new therapeutic option for myocardial infarction (MI). The tissue matrix metalloproteinase inhibitor 2, also known as TIMP2, is a member of the tissue inhibitor family of metalloproteinases. Since TIMP2-mediated inhibition of matrix metalloproteinases (MMPs) is a key determinant of post-MI remodeling, we analyzed the therapeutic effects of exosomes derived from TIMP2-overexpressing hucMSCs (huc-exoTIMP2) on the MI rat model. The huc-exoTIMP2 significantly improved in vivo cardiac function as measured by echocardiography and promoted angiogenesis in MI injury. It also restricted extracellular matrix (ECM) remodeling, as indicated by the reduced collagen deposition. In addition, huc-exoTIMP2 administration increased the in situ expression of the antiapoptotic Bcl-2 and decreased that of the proapoptotic Bax and pro-caspase-9 in the infracted myocardium. Meanwhile, huc-exoTIMP2 upregulated superoxide dismutase (SOD) as well as glutathione (GSH) and decreased the malondialdehyde (MDA) level in MI models. In vitro huc-exoTIMP2 pretreatment could inhibit H2O2-mediated H9C2-cardiomyocyte apoptosis and promote human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation, as well as decrease TGFβ-induced MMP2, MMP9, and α-SMA secretion by cardiac fibroblasts (CFs). Besides that, huc-exoTIMP2 pretreatment also increased the expression of Akt phosphorylation in the infarcted myocardium, which may relate to a high level of secreted frizzled-related protein 2 (Sfrp2) in huc-exoTIMP2, indicating a mechanistic basis of its action. Importantly, Sfrp2 knockdown in huc-exoTIMP2 abrogated the protective effects. Taken together, huc-exoTIMP2 improved cardiac function by alleviating MI-induced oxidative stress and ECM remodeling, partly via the Akt/Sfrp2 pathway.
The conversion of skeletal muscle fiber from fast twitch to slow‐twitch is important for sustained and tonic contractile events, maintenance of energy homeostasis, and the alleviation of fatigue. Skeletal muscle remodeling is effectively induced by endurance or aerobic exercise, which also generates several tricarboxylic acid ( TCA ) cycle intermediates, including succinate. However, whether succinate regulates muscle fiber‐type transitions remains unclear. Here, we found that dietary succinate supplementation increased endurance exercise ability, myosin heavy chain I expression, aerobic enzyme activity, oxygen consumption, and mitochondrial biogenesis in mouse skeletal muscle. By contrast, succinate decreased lactate dehydrogenase activity, lactate production, and myosin heavy chain II b expression. Further, by using pharmacological or genetic loss‐of‐function models generated by phospholipase Cβ antagonists, SUNCR 1 global knockout, or SUNCR 1 gastrocnemius‐specific knockdown, we found that the effects of succinate on skeletal muscle fiber‐type remodeling are mediated by SUNCR 1 and its downstream calcium/ NFAT signaling pathway. In summary, our results demonstrate succinate induces transition of skeletal muscle fiber via SUNCR 1 signaling pathway. These findings suggest the potential beneficial use of succinate‐based compounds in both athletic and sedentary populations.
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