Inhibition of nuclear factor-κB by 6-O-acetyl shanzhiside methyl ester protects brain against injury in a rat model of ischemia and reperfusion

<p>Abstract</p> <p>Background</p> <p>Recent studies have demonstrated an inflammatory response associated with the pathophysiology of cerebral ischemia. The beneficial effects of anti-inflammatory drugs in cerebral ischemia have been documented. When screening natural compounds for drug candidates in this category, we isolated 6-O-acetyl shanzhiside methyl ester (ND02), an iridoid glucoside compound, from the leaves of <it>Lamiophlomis rotata (Benth.) Kudo</it>. The objectives of this study were to determine the effects of ND02 on a cultured neuronal cell line, SH-SY5Y, in vitro, and on experimental ischemic stroke in vivo.</p> <p>Methods</p> <p>For TNF-α-stimulated SH-SY5Y cell line experiments in vitro, SH-SY5Y cells were pre-incubated with ND02 (20 μM or 40 μM) for 30 min and then incubated with TNF-α (20 ng/ml) for 15 min. For in vivo experiments, rats were subjected to middle cerebral artery occlusion (MCAO) for 1 h followed by reperfusion for 23 h.</p> <p>Results</p> <p>ND02 treatment of SH-SY5Y cell lines blocked TNF-α-induced nuclear factor-κB (NF-κB) and IκB-α phosphorylation and increased Akt phosphorylation. LY294002 blocked TNF-α-induced phosphorylation of Akt and reduced the phosphorylation of both IκB-α and NF-κB. At doses higher than 10 mg/kg, ND02 had a significant neuroprotective effect in rats with cerebral ischemia and reperfusion (I/R). ND02 (25 mg/kg) demonstrated significant neuroprotective activity even after delayed administration 1 h, 3 h and 5 h after I/R. ND02, 25 mg/kg, attenuated histopathological damage, decreased cerebral Evans blue extravasation, inhibited NF-κB activation, and enhanced Akt phosphorylation.</p> <p>Conclusion</p> <p>These data show that ND02 protects brain against I/R injury with a favorable therapeutic time-window by alleviating cerebral I/R injury and attenuating blood-brain barrier (BBB) breakdown, and that these protective effects may be due to blocking of neuronal inflammatory cascades through an Akt-dependent NF-κB signaling pathway.</p

Short supply chain, technical efficiency, and technological change: Insights from cucumber production

This study examines the impact of participation in short supply chains (SSCs) on technical efficiency (TE) and technological change (TC) in cucumber production in China, using data for the period 2011–2016. The meta‐frontier model and the two‐stage residual inclusion approach are utilized to examine the association between SSC participation, comparable TE, and TC. Accounting for selection bias, we show that SSC participation significantly decreased the comparable TE of cucumber production but accelerated TC. The disaggregated analysis reveals that the comparable TE for SSC participants was generally smaller than that for nonparticipants. Furthermore, comparable TE for nonparticipants consistently increased year‐over‐year, whereas, for SSC participants, it increased during some years and decreased during others. Last but not least, TC for both SSC participants and nonparticipants increased over time

Impact of cash crop cultivation on household income and migration decisions: Evidence from low-income regions in China

This study examines the impact of cash crop cultivation on household income and migration decisions, using survey data collected from low-income regions in China. Given farmers decide themselves whether to cultivate cash crops, an endogenous treatment regression model that accounts for potential selection bias issue is used to analyze the data. The empirical results show that cash crop cultivation exerts a positive and statistically significant impact on household income, but it does not affect household migration decisions significantly. The disaggregated analyses reveal that cash crop cultivation significantly increases farm income but decreases off-farm income

Economic downturns and leisure in China

This study examines the impact of economic downturns on leisure life, using the Chinese General Social Survey data from 2010 to 2015. The results show that economic downturns significantly decrease individuals’ time allocated to leisure activities. Specifically, participation in educational activities increases during economic downturns, while participation in social interaction and entertainment does not change. We also find that economic downturns significantly reduce the average frequency of individuals’ participation in active entertainment activities (e.g. reading, participating in cultural activities, listening to music at home, participating in physical exercise, watching live sports games, and doing handwork), but do not significantly affect the average frequency of individuals’ participation in passive entertainment activities (e.g. watching TV or DVD at home, watching movies in a cinema, shopping, gathering with relatives, gathering with friends, and surfing the Internet)

Saquinavir plus methylprednisolone ameliorates experimental acute lung injury

Glucocorticoid insensitivity is an important barrier to the treatment of several inflammatory diseases, including acute lung injury (ALI). Saquinavir (SQV) is an inhibitor of the human immunodeficiency virus protease, and the therapeutic effects of SQV in ALI accompanied with glucocorticoid insensitivity have not been previously investigated. In this study, the effects of SQV on lipopolysaccharide (LPS)-mediated injury in human pulmonary microvascular endothelial cells (HPMECs), human type I alveolar epithelial cells (AT I), and alveolar macrophages were determined. In addition, the effects of SQV on an LPS-induced ALI model with or without methylprednisolone (MPS) were studied. In LPS-stimulated HPMECs, SQV treatment resulted in a decrease of high mobility group box 1 (HMGB1), phospho-NF-κB (p-NF-κB), and toll-like receptor 4 (TLR4), and an increase of VE-cadherin. Compared to MPS alone, MPS plus SQV attenuated the decrease of glucocorticoid receptor alpha (GRα) and IκBα in LPS-stimulated HPMECs. HMGB1, TLR4, and p-NF-κB expression were also lessened in LPS-stimulated alveolar macrophages with SQV treatment. In addition, SQV reduced the injury in human AT I with a decrease of HMGB1 and p-NF-κB, and with an increase of aquaporin 5 (AQP 5). SQV ameliorated the lung injury caused by LPS in rats with reductions in vascular permeability, myeloperoxidase activity (MPO) and histopathological scores, and with lowered HMGB1, TLR4, and p-NF-κB expression, but with enhanced VE-cadherin expression. By comparison, SQV plus MPS increased GRα and IκBα in lung tissues of rats with ALI. This study demonstrated that SQV prevented experimental ALI and improved glucocorticoid insensitivity by modulating the HMGB1/TLR4 pathway

Cold sintering of perovskite‐based mixed conducting membrane for oxygen separation

Cold sintering has attracted significant attention as its remarkably rapid densification process at low sintering temperatures leads to considerable energy savings. However, the sintering behaviors of cold‐sintered perovskite ceramics remain poorly understood and lack precise control over material microstructure. Here, we fabricated dense SrCo0.8Fe0.2O3−δ (SCF) ceramic oxygen permeation membranes by cold sintering. Adding an appropriate ratio of sub‐micron SCF particles can better bridge the sintering interspaces between micron particles, generate amorphous phase through “dissolution‐precipitation,” and aid in the initial densification. The average relative density of SCF membranes undergoes a significant increase to 95.9% after cold sintering and post‐annealing at 900°C, which is much lower than the temperature required for conventional high‐temperature solid‐state sintering (>1200°C). The oxygen permeation flux of the prepared SCF perovskite membrane reaches 2.8 mL min−1 cm−2, which proves that this method has the potential to be an excellent sintering technique for dense perovskite ceramic membranes

Saquinavir plus methylprednisolone ameliorates experimental acute lung injury

<div><p>Glucocorticoid insensitivity is an important barrier to the treatment of several inflammatory diseases, including acute lung injury (ALI). Saquinavir (SQV) is an inhibitor of the human immunodeficiency virus protease, and the therapeutic effects of SQV in ALI accompanied with glucocorticoid insensitivity have not been previously investigated. In this study, the effects of SQV on lipopolysaccharide (LPS)-mediated injury in human pulmonary microvascular endothelial cells (HPMECs), human type I alveolar epithelial cells (AT I), and alveolar macrophages were determined. In addition, the effects of SQV on an LPS-induced ALI model with or without methylprednisolone (MPS) were studied. In LPS-stimulated HPMECs, SQV treatment resulted in a decrease of high mobility group box 1 (HMGB1), phospho-NF-κB (p-NF-κB), and toll-like receptor 4 (TLR4), and an increase of VE-cadherin. Compared to MPS alone, MPS plus SQV attenuated the decrease of glucocorticoid receptor alpha (GRα) and IκBα in LPS-stimulated HPMECs. HMGB1, TLR4, and p-NF-κB expression were also lessened in LPS-stimulated alveolar macrophages with SQV treatment. In addition, SQV reduced the injury in human AT I with a decrease of HMGB1 and p-NF-κB, and with an increase of aquaporin 5 (AQP 5). SQV ameliorated the lung injury caused by LPS in rats with reductions in vascular permeability, myeloperoxidase activity (MPO) and histopathological scores, and with lowered HMGB1, TLR4, and p-NF-κB expression, but with enhanced VE-cadherin expression. By comparison, SQV plus MPS increased GRα and IκBα in lung tissues of rats with ALI. This study demonstrated that SQV prevented experimental ALI and improved glucocorticoid insensitivity by modulating the HMGB1/TLR4 pathway.</p></div

Tris-(2,3-Dibromopropyl) Isocyanurate, a New Emerging Pollutant, Impairs Cognition and Provokes Depression-Like Behaviors in Adult Rats.

Tris-(2,3-dibromopropyl) isocyanurate (TDBP-TAZTO), an emerging brominated flame retardant, possesses the characteristics of candidate persistent organic pollutants and has displayed toxicity to fish and rodents. TDBP-TAZTO can pass through the blood brain barrier and accumulate in brain. However, the neurotoxicity of TDBP-TAZTO has not yet studied in rodents. We hypothesize that TDBP-TAZTO could induce the neurotoxicity in rat hippocampal neurons. The male adult rats were exposed to TDBP-TAZTO of 5 and 50 mg/kg by gavage, daily for 6 months. TDBP-TAZTO resulted in cognitive impairment and depression-like behaviors, which may be related with TDBP-TAZTO-induced hypothalamic-pituitary-adrenal axis hyperactivation, upregulation of inflammatory and oxidative stress markers, overexpression of pro-apoptotic proteins, downexpression of neurogenesis-related proteins in hippocampus, and hippocampal neurons damage in DG, CA1 and CA3 areas. Our findings suggested that TDBP-TAZTO induces significant hippocampal neurotoxicity, which provokes cognitive impairment and depression-like behaviors in adult rats. Therefore, this research will contribute to evaluate the neurotoxic effects of TDBP-TAZTO in human