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Endogenous hydrogen sulfide (H(2)S) is naturally synthesized in various types of mammalian cells from l-cysteine in a reaction catalyzed by two enzymes, cystathionine-gamma-lyase (CSE) and/or cystathionine-beta-synthase. The latest studies have implied that H(2)S functions as a vasodilator and neurotransmitter. However, so far there is little information about the role played by H(2)S in systemic inflammation such as sepsis. Thus the aim of this study was to investigate the potential role of endogenous H(2)S in cecal ligation and puncture (CLP)-induced sepsis. Male Swiss mice were subjected to CLP-induced sepsis and treated with saline (ip), dl-propargylglycine (PAG, 50 mg/kg ip), a CSE inhibitor, or sodium hydrosulfide (NaHS; 10 mg/kg ip). PAG was administered either 1 h before or 1 h after the induction of sepsis, whereas NaHS was given at the same time of CLP. CLP-induced sepsis significantly increased the plasma H(2)S level and the liver H(2)S synthesis 8 h after CLP compared with sham operation. Induction of sepsis also resulted in a significant upregulation of CSE mRNA in liver. On the other hand, prophylactic as well as therapeutic administration of PAG significantly reduced sepsis-associated systemic inflammation, as evidenced by myeloperoxidase activity and histological changes in lung and liver, and attenuated the mortality of CLP-induced sepsis. Injection of NaHS significantly aggravated sepsis-associated systemic inflammation. Therefore, the effect of inhibition of H(2)S formation and administration of NaHS suggests that H(2)S plays a proinflammatory role in regulating the severity of sepsis and associated organ injury.

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Hydrogen sulfide (H2S) is now considered an endogenous, gaseous mediator, which has been demonstrated to be involved in many inflammatory states. However, the mechanism of its proinflammatory function remains unknown. In the present study, we used IFN-gamma-primed human monocytic cell line U937 to investigate the effects of H2S in vitro on monocytes. We found that treatment with the H2S donor, sodium hydrosulfide, led to significant increases in the mRNA expression and protein production of TNF-alpha, IL-1beta, and IL-6 in U937 cells. H2S-triggered monocyte activation was confirmed further by the up-regulation of CD11b expression on the cell surface. We also observed that H2S could induce a rapid degradation of IkappaBalpha and subsequent activation of NF-kappaB p65, and this effect was attenuated by Bay 11-7082, a specific inhibitor of NF-kappaB. Furthermore, pretreatment of cells with Bay 11-7082 substantially inhibited the secretion of TNF-alpha, IL-1beta, and IL-6 induced by H2S. We also found that H2S stimulated the phosphorylation and activation of ERK1/2, but not of p38 MAPK and JNK, and pretreatment with PD98059, a selective MEK1 antagonist, could inhibit H2S-induced NF-kappaB activation markedly. Together, our findings suggest for the first time that H2S stimulates the activation of human monocytes with the generation of proinflammatory cytokines, and this response is, at least partially, through the ERK-NF-kappaB signaling pathway.

Nanostructured mesoporous manganese oxides were easily prepared by mixing KMnO 4 with ascorbic acid in an aqueous solution under ambient conditions. The obtained manganese oxides were identified as having an R-MnO 2 tunnel structure composed of an edge-shared network of [MnO 6 ] octahedra. TEM observations revealed that the obtained MnO 2 materials had three-dimensional frameworks which consisted of homogeneous nanoparticles with sizes of ca. 5 nm. Nitrogen sorption analyses showed that these MnO 2 nanoparticles exhibited a type IV isotherm, indicating a mesoporous character. Large surface areas up to 284 m 2 g À1 were recorded. The electrochemical performances of the synthesized R-MnO 2 nanoparticles as supercapacitor electrode materials were studied using cyclic voltammetry and galvanostatic chargeÀdischarge cycling in a threeelectrode system at a potential range from 0 to 1.0 V vs a saturated calomel electrode in 0.5 M sodium sulfate solution. The result showed that mesoporous MnO 2 with three-dimensional frameworks exhibit a high capacitance up to ∼200 F g À1 . Furthermore, a hybrid supercapacitor was assembled by using MnO 2 mixed with a small amount of activated carbon as the positive electrode and activated carbon as the negative electrode in a 0.5 M Na 2 SO 4 electrolyte. By balancing the mass of MnO 2 and activated carbon, a practical cell voltage of 1.8 V could be obtained in aqueous medium with a capacitance of 23.1 F g À1 . After 1200 cycles, the maximum energy density is 10.4 Wh kg À1 and power density is 14.7 kW kg À1 . Thus, the obtained R-MnO 2 nanoparticles are suitable for use as supercapacitor electrode materials.