Int J Clin Exp Patho
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Int J Clin Exp Patho · Jan 2015
Delayed cardioprotection by sevoflurane preconditioning: a novel mechanism via inhibiting Beclin 1-mediated autophagic cell death in cardiac myocytes exposed to hypoxia/reoxygenation injury.
Sevoflurane preconditioning has shown to exert delayed caridioprotection against subsequent ischemia and reperfusion injury, but the mechanisms underlying is unclear. Inhibition of autophagy by 3-methyladenine (3-MA) or knockdown of Beclin 1 leads to enhanced cardiac myocyte survival. Our study aimed to test whether sevoflurane preconditioning provides a second window of anesthetic preconditioning (SWOP) via inhibit Beclin 1-mediated autophagic cell death. ⋯ H/R injury up-regulated the expression of LC3-II and Beclin 1 proteins (342 ± 66% and 163 ± 18%, respectively, P < 0.05) compared to the CON group (100%), which were increased in SWOP group (202 ± 77% and 128 ± 8%, respectively, P < 0.05). The expression of LC3-II and Beclin 1 proteins was decreased in 3-MA group (110 ± 28% and 97 ± 6%, respectively) and 3-MA+SWOP group (93 ± 7% and 98 ± 6%, respectively) compared with H/R group, but Bcl-2 was upregulated in 3-MA group (158 ± 4%) and 3-MA+SWOP group (156 ± 5%) compared to H/R group (103 ± 7%). In conclusion, sevoflurane preconditioning confers delayed cardioprotection via inhibition Beclin 1-mediated autophagic cell death in cardiac myocytes 24 h before exposed to H/R injury.
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Int J Clin Exp Patho · Jan 2015
Development of a KLD-12 polypeptide/TGF-β1-tissue scaffold promoting the differentiation of mesenchymal stem cell into nucleus pulposus-like cells for treatment of intervertebral disc degeneration.
To develop tissue engineering scaffolds consisting of self-assembling KLD-12 polypeptide/TGF-β1 nanofiber gel, for the induction of mesenchymal stem cell (MSCs) differentiation into nucleus pulposus (NP)-like cells. ⋯ A scaffold containing a KLD-12 polypeptide/TGF-β1-nanofiber gel and MSCs differentiated into NP-like cells is able to produce ECM and has the potential to serve as a three-dimensional (3-D) support scaffold for the filling of early postoperative residual cavities and the treatment of intervertebral disc degeneration.
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Int J Clin Exp Patho · Jan 2015
An exogenous hydrogen sulphide donor, NaHS, inhibits the apoptosis signaling pathway to exert cardio-protective effects in a rat hemorrhagic shock model.
Hydrogen sulfide (H2S) has been reported to be interwined in multiple systems, specifically in the cardiovascular system. However, the mechanisms underlying remain controversial. In the present study, we assessed the cardio-protective effects of H2S in the rat hemorrhagic shock model. ⋯ Moreover, the expression of death receptor Fas and Fas-ligand, as well as the expression of apoptosis-relevant proteins active-caspase 3 and active-caspase 8 were markedly increased. Administration of NaHS significantly ameliorated hemorrhagic shock caused hemodynamic deterioration, decreased myocardial enzymes elevation, protected myocardial ultrastructure, and inhibited the expression of apoptosis-relevant proteins. It suggested that H2S might exert its cardio-protective roles via both the extrinsic Fas/FasL/caspase-8/caspase-3 pathway and the intrinsic mitochondria-involved pathways.
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Int J Clin Exp Patho · Jan 2015
Platelet-derived microvesicles are involved in cardio-protective effects of remote preconditioning.
The ischemia-protective mechanism of remote precondition has been a mystery for a long time. Little was known about details of the inter-organ cardio-protective. Microvesicles, also known as microparticles (MPs), are small membrane-vesicles budding from the plasma membrane of cell. ⋯ We further observed the contractile function in hearts after they were subjected to different treatments. However, no significant difference was observed in transfusion of MPs from rats that underwent RIPC in 6 hours. RIPC induces an increase in MPs, and platelet-derived MPs may confer at least part of the remote protective effect against cardiac ischemic-reperfusion injury.
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Int J Clin Exp Patho · Jan 2015
Activation of α2 adrenoceptor attenuates lipopolysaccharide-induced hepatic injury.
Sepsis induces hepatic injury but whether alpha-2 adrenoceptor (α2-AR) modulates the severity of sepsis-induced liver damage remains unclear. The present study used lipopolysaccharide (LPS) to induce hepatic injury and applied α2-AR agonist dexmedetomidine (DEX) and/or antagonist yohimbine to investigate the contribution of α2-AR in LPS-induced liver injury. ⋯ Activation of α2-AR by dexmedetomidine (DEX) attenuated LPS-induced deleterious effects on the liver and block of α2-AR by yohimbine aggravated LPS-induced liver damage. Our data suggest that α2-AR plays an important role in sepsis-induced liver damage and activation of α2-AR with DEX could be a novel therapeutic avenue to protect the liver against sepsis-induced injury.