Nephroprotective role of resveratrol and ursolic acid in aristolochic acid intoxicated zebrafish

[[incitationindex]]SCI[[booktype]]電子

Extracellular signal-regulated kinase 1/2 plays a pro-life role in experimental brain stem death via MAPK signal-interacting kinase at rostral ventrolateral medulla

<p>Abstract</p> <p>Background</p> <p>As the origin of a life-and-death signal detected from systemic arterial pressure, which sequentially increases (pro-life) and decreases (pro-death) to reflect progressive dysfunction of central cardiovascular regulation during the advancement towards brain stem death in critically ill patients, the rostral ventrolateral medulla (RVLM) is a suitable neural substrate for mechanistic delineation of this fatal phenomenon. The present study assessed the hypothesis that extracellular signal-regulated kinase 1/2 (ERK1/2), a member of the mitogen-activated protein kinases (MAPKs) that is important for cell survival and is activated specifically by MAPK kinase 1/2 (MEK1/2), plays a pro-life role in RVLM during brain stem death. We further delineated the participation of MAPK signal-interacting kinase (MNK), a novel substrate of ERK in this process.</p> <p>Methods</p> <p>An experimental model of brain stem death that employed microinjection of the organophosphate insecticide mevinphos (Mev; 10 nmol) bilaterally into RVLM of Sprague-Dawley rats was used, in conjunction with cardiovascular, pharmacological and biochemical evaluations.</p> <p>Results</p> <p>Results from ELISA showed that whereas the total ERK1/2 was not affected, augmented phosphorylation of ERK1/2 at Thr202 and Tyr204 in RVLM occurred preferentially during the pro-life phase of experimental brain stem death. Furthermore, pretreatment by microinjection into the bilateral RVLM of a specific ERK2 inhibitor, ERK activation inhibitor peptide II (1 nmol); a specific MEK1/2 inhibitor, U0126 (5 pmol); or a specific MNK1/2 inhibitor, CGP57380 (5 pmol) exacerbated the hypotension and blunted the augmented life-and-death signals exhibited during the pro-life phase. Those pretreatments also blocked the upregulated nitric oxide synthase I (NOS I)/protein kinase G (PKG) signaling, the pro-life cascade that sustains central cardiovascular regulatory functions during experimental brain stem death.</p> <p>Conclusions</p> <p>Our results demonstrated that activation of MEK1/2, ERK1/2 and MNK1/2 in RVLM plays a preferential pro-life role by sustaining the central cardiovascular regulatory machinery during brain stem death via upregulation of NOS I/PKG signaling cascade in RVLM.</p

Asynchronous adaptive time step in quantitative cellular automata modeling

BACKGROUND: The behaviors of cells in metazoans are context dependent, thus large-scale multi-cellular modeling is often necessary, for which cellular automata are natural candidates. Two related issues are involved in cellular automata based multi-cellular modeling: how to introduce differential equation based quantitative computing to precisely describe cellular activity, and upon it, how to solve the heavy time consumption issue in simulation. RESULTS: Based on a modified, language based cellular automata system we extended that allows ordinary differential equations in models, we introduce a method implementing asynchronous adaptive time step in simulation that can considerably improve efficiency yet without a significant sacrifice of accuracy. An average speedup rate of 4–5 is achieved in the given example. CONCLUSIONS: Strategies for reducing time consumption in simulation are indispensable for large-scale, quantitative multi-cellular models, because even a small 100 × 100 × 100 tissue slab contains one million cells. Distributed and adaptive time step is a practical solution in cellular automata environment

Case study on user knowledge and design knowledge in product form design

2003-2004 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Stored energy in metallic glasses due to strains within the elastic limit

Room-temperature loading of metallic glasses, at stresses below the macroscopic yield stress, raises their enthalpy and causes creep. Thermal cycling of metallic glasses between room temperature and 77 K also raises their enthalpy. In both cases, the enthalpy increases are comparable to those induced by heavy plastic deformation, but, as we show, the origins must be quite different. For plastic deformation, the enthalpy increase is a fraction (<10%) of the work done (and, in this sense, the behaviour is similar to that of conventional polycrystalline metals and alloys). In contrast, the room-temperature creep and the thermal cycling involve small strains, well within the elastic limit; in these cases the enthalpy increase in the glass exceeds the work done, by as much as three orders of magnitude. We argue that the increased enthalpy can arise only from an endothermic disordering process drawing heat from the surroundings. We examine the mechanisms of this process. The increased enthalpy (‘stored energy’) is a measure of rejuvenation, and appears as an exothermic heat of relaxation on heating the glass. The profile of this heat release (the ‘relaxation spectrum’) is analysed for several metallic glasses subjected to various treatments. Thus the effects of the small-strain processing (creep and thermal cycling) can be better understood, and we can explore the potential for improving properties, in particular the plasticity, of metallic glasses. Metallic glasses can exhibit a wide range of enthalpy at a given temperature, and small-strain processing may assist in accessing this for practical purposes.A.L.G. was supported by the Engineering and the Engineering and Physical Sciences Research Council, UK (grant EP/I035404/1) and the World Premier International Research Center Initiative (WPI), MEXT, Japan; Y.H.S. was supported by a China Scholarship Council (CSC) scholarship.This is the final version of the article. It first appeared from Taylor & Francis via https://doi.org/ 10.1080/14786435.2016.117723

Flow-induced elastic anisotropy of metallic glasses

As-cast bulk metallic glasses are isotropic, but anisotropy can be induced by thermomechanical treatments. For example, the diffraction halo in the structure function S(Q) observed in transmission becomes elliptical (rather than circular) after creep in uniaxial tension or compression. Published studies associate this with frozen-in anelastic strain and bond-orientational anisotropy. Results so far are inconsistent on whether viscoplastic flow of metallic glasses can induce anisotropy. Preliminary diffraction data suggest that the anisotropy, if any, is very low, while measurements of the elastic properties suggest that there is induced anisotropy, opposite in sign to that due to anelastic strain. We study three bulk metallic glasses, Ce65Al10Cu20Co5, La55Ni10Al35, and Pd40Ni30Cu10P20. By using resonant ultrasound spectroscopy to determine the full elasticity tensor, the effects of relaxation and rejuvenation can be reliably separated from uniaxial anisotropy (of either sign). The effects of viscoplastic flow in tension are reported for the first time. We find that viscoplastic flow of bulk metallic glasses, particularly in tension, can induce significant anisotropy that is distinct from that associated with frozen-in anelastic strain. The conditions for inducing such anisotropy are explored in terms of the Weissenberg number (ratio of relaxation times for primary relaxation and for shear strain rate). There is a clear need for further work to characterize the structural origins of flow-induced anisotropy and to explore the prospects for improved mechanical and other properties through induced anisotropy.This research was supported by the Engineering and the Engineering and Physical Sciences Research Council, UK (grant EP/I035404/1). Y.H.S. acknowledges support from a China Scholarship Council (CSC) scholarship. The authors thank Z. Lu, H. Y. Bai and W. H. Wang for the supply of the Ce65Al10Cu20Co5 and La55Ni20Al25 metallic glasses.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.actamat.2016.04.02

ITPKA expression is a novel prognostic factor in hepatocellular carcinoma

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Prognostic Significance of Fam3c in Esophageal Squamous Cell Carcinoma

Background: Family with sequence similarity 3, member C (FAM3C) has been identified as a novel regulator in epithelial-mesenchymal transition (EMT) and metastatic progression. However, the role of FAM3C in esophageal squamous cell carcinoma (ESCC) remains unexplored. The purpose of present study is to illustrate the role of FAM3C in predicting outcomes of patients with ESCC. Methods: FAM3C expression was measured in ESCC tissues and the matched adjacent nontumorous tissues by quantitative real-time RT-PCR and Western blot analysis. The relationship between FAM3C expression and prognosis of ESCC patients was further evaluated by univariate and multivariate regression analyses. Univariate and multivariate analyses of the prognostic factors were performed using Cox proportional hazards model. Results: The FAM3C mRNA expression was remarkably upregulated in ESCC compared with their nontumor counterparts (P < 0.001). In addition, high expression of FAM3C was significantly associated with pT stage (P = 0.014) , pN stage (P = 0.026) and TNM stage (P = 0.003). Kaplan-Meier analysis showed that the 7-year overall survival rate in the group with high expression of FAM3C was poorer than that in low expression group (32.0 versus 70.9 %; P < 0.001). Univariate and multivariate analyses demonstrated that FAM3C was an independent risk factor for overall survival. Moreover, Stratified analysis revealed that FAM3C expression could differentiate the prognosis of patients in early clinical stage (TNM stage I-II). Conclusions:FAM3C expression was dramatically increased in ESCC and might serve as a valuable prognostic indicator for ESCC patients after surgery. © 2015 Zhu et al.published_or_final_versio

Differential regulation of cytokine-and phorbol ester-induced activation of nuclear factor kappa B by Pseudomonas aeruginosa pyocyanin in human airway epithelial cells

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