Ginkgolide B Reduces Atherogenesis and Vascular Inflammation in ApoE−/− Mice

To investigate whether ginkgolide B (a platelet-activating factor inhibitor) affects vascular inflammation in atherosclerosis-prone apolipoprotein E-deficient (ApoE(-/-)) mice.Human platelets were used to evaluate the effects of ginkgolide B on platelet aggregation and signal transduction. Ginkgolide B attenuated platelet aggregation and inhibited phosphatidylinositol 3 kinase (PI3K) activation and Akt phosphorylation in thrombin- and collagen-activated platelets. ApoE(-/-) mice were administered a high-cholesterol diet for 8 weeks. Plasma platelet factor 4 (PF4) and RANTES (regulated upon activation, normal T-cell expressed, and secreted protein) were then measured using an enzyme-linked immunosorbent assay. Scanning electron microscopy and immunohistochemistry were used to determine atherosclerotic lesions. Ginkgolide B decreased plasma PF4 and RANTES levels in ApoE(-/-) mice. Scanning electron microscopic examination showed that ginkgolide B reduced aortic plaque in ApoE(-/-) mice. Immunohistochemistry analysis demonstrated that ginkgolide B diminished P-selectin, PF4, RANTES, and CD40L expression in aortic plaque in ApoE(-/-) mice. Moreover, ginkgolide B suppressed macrophage and vascular cell adhesion protein 1 (VCAM-1) expression in aorta lesions in ApoE(-/-) mice. Similar effects were observed in aspirin-treated ApoE(-/-) mice.Ginkgolide B significantly reduced atherosclerotic lesions and P-selectin, PF4, RANTES, and CD40L expression in aortic plaque in ApoE-/- mice. The efficacy of ginkgolide B was similar to aspirin. These results provide direct evidence that ginkgolide B inhibits atherosclerosis, which may be associated with inhibition of the PI3K/Akt pathway in activated platelets

Ginkgolide B Inhibits JAM-A, Cx43, and VE-Cadherin Expression and Reduces Monocyte Transmigration in Oxidized LDL-Stimulated Human Umbilical Vein Endothelial Cells

Aim. To investigate the effect of ginkgolide B on junction proteins and the reduction of monocyte migration in oxidized low-density lipoprotein- (ox-LDL-) treated endothelial cells. Methods. Human umbilical vein endothelial cells (HUVECs) were used in the present study. Immunofluorescence and Western blot were performed to determine the expression of junctional adhesion molecule-A (JAM-A), connexin 43 (Cx43), and vascular endothelial cadherin (VE-cadherin). Monocyte migration was detected by the Transwell assay. Results. ox-LDL stimulation increased JAM-A expression by 35%, Cx43 expression by 24%, and VE-cadherin expression by 37% in HUVECs. Ginkgolide B (0.2, 0.4, and 0.6 mg/mL) dose-dependently abolished the expression of these junction proteins. The monocyte transmigration experiments showed that the level of monocyte migration was sixfold higher in the ox-LDL-treated group than in the control group. Ginkgolide B (0.6 mg/mL) nearly completely abolished monocyte migration. Both ginkgolide B and LY294002 suppressed Akt phosphorylation and the expression of these junction proteins in ox-LDL-treated endothelial cells. These results suggest that the ginkgolide B-induced inhibition of junction protein expression is associated with blockade of the PI3K/Akt pathway. Conclusion. Ginkgolide B suppressed junction protein expression and reduced monocyte transmigration that was induced by ox-LDL. Ginkgolide B may improve vascular permeability in atherosclerosis

Genome-wide identification of resistance genes and response mechanism analysis of key gene knockout strain to catechol in Saccharomyces cerevisiae

Engineering Saccharomyces cerevisiae for biodegradation and transformation of industrial toxic substances such as catechol (CA) has received widespread attention, but the low tolerance of S. cerevisiae to CA has limited its development. The exploration and modification of genes or pathways related to CA tolerance in S. cerevisiae is an effective way to further improve the utilization efficiency of CA. This study identified 36 genes associated with CA tolerance in S. cerevisiae through genome-wide identification and bioinformatics analysis and the ERG6 knockout strain (ERG6Δ) is the most sensitive to CA. Based on the omics analysis of ERG6Δ under CA stress, it was found that ERG6 knockout affects pathways such as intrinsic component of membrane and pentose phosphate pathway. In addition, the study revealed that 29 genes related to the cell wall-membrane system were up-regulated by more than twice, NADPH and NADP+ were increased by 2.48 and 4.41 times respectively, and spermidine and spermine were increased by 2.85 and 2.14 times, respectively, in ERG6Δ. Overall, the response of cell wall-membrane system, the accumulation of spermidine and NADPH, as well as the increased levels of metabolites in pentose phosphate pathway are important findings in improving the CA resistance. This study provides a theoretical basis for improving the tolerance of strains to CA and reducing the damage caused by CA to the ecological environment and human health

Relationships between Stress Granules, Oxidative Stress, and Neurodegenerative Diseases

Cytoplasmic stress granules (SGs) are critical for facilitating stress responses and for preventing the accumulation of misfolded proteins. SGs, however, have been linked to the pathogenesis of neurodegenerative diseases, in part because SGs share many components with neuronal granules. Oxidative stress is one of the conditions that induce SG formation. SGs regulate redox levels, and SG formation in turn is differently regulated by various types of oxidative stress. These associations and other evidences suggest that SG formation contributes to the development of neurodegenerative diseases. In this paper, we review the regulation of SG formation/assembly and discuss the interactions between oxidative stress and SG formation. We then discuss the links between SGs and neurodegenerative diseases and the current therapeutic approaches for neurodegenerative diseases that target SGs

Relationships between Stress Granules, Oxidative Stress, and Neurodegenerative Diseases

Cytoplasmic stress granules (SGs) are critical for facilitating stress responses and for preventing the accumulation of misfolded proteins. SGs, however, have been linked to the pathogenesis of neurodegenerative diseases, in part because SGs share many components with neuronal granules. Oxidative stress is one of the conditions that induce SG formation. SGs regulate redox levels, and SG formation in turn is differently regulated by various types of oxidative stress. These associations and other evidences suggest that SG formation contributes to the development of neurodegenerative diseases. In this paper, we review the regulation of SG formation/assembly and discuss the interactions between oxidative stress and SG formation. We then discuss the links between SGs and neurodegenerative diseases and the current therapeutic approaches for neurodegenerative diseases that target SGs

Numerical study on effects of EGR on combustion and NOx emissions of gasoline blended dissociated methanol gas engine

Exhaust gas recirculation (EGR), which can reduce NOx emissions effectively, has been widely studied in engines, but there are few studies using EGR on gasoline blended dissociated methanol gas (GDM) engines. To reduce the NOx emissions of GDM engines, investigation is conducted based on numerical simulation in this study. The accuracy of the engine numerical model is first validated through experimental data, and then the effects of EGR on GDM engine performance are studied, including combustion characteristics and NOx emissions. Numerical simulation results show that the application of EGR reduces the cylinder pressure and the heat release rate of GDM engine, and delays the corresponding crank angle of their peak value respectively. The application of EGR also delays the combustion center, and extends the ignition delay and combustion duration. As EGR rate increases, the NOx emissions decrease significantly. This study offers valuable insights into the potential application of EGR technology in GDM engines

Impact of preparation methods on the performance of Cu/Ni/Zr catalysts for methanol decomposition

Utilizing waste heat from engine exhausts to decompose methanol into a hydrogen (H _2 ) and carbon monoxide (CO) mixture, subsequently reintroduced into the engine, offers a significant potential to enhance engine efficiency and reduce emissions. The efficacy of the catalyst is crucial, as it directly influences the composition of the decomposition gases, thereby impacting energy conservation and emissions reduction. This study investigates the impact of various preparation methods for the self-developed Cu/Ni/Zr catalyst for methanol hydrogenation decomposition. These techniques include the co-precipitation method, co-impregnation method, and citrate complexation method, evaluated within a temperature spectrum of 220 °C–320 °C. Employing analytical methods such as x-ray Photoelectron Spectroscopy (XPS), x-ray Diffraction (XRD), Thermogravimetric Analysis-Differential Scanning Calorimetry (TGA-DSC), Brunauer–Emmett–Teller (BET), Temperature-Programmed Reduction (TPR), and Scanning Electron Microscopy (SEM) analysis, the study elucidates the mechanism of methanol decomposition catalyzed by Cu/Ni/Zr. The findings indicate that the catalyst’s activity, in terms of decomposition rate and hydrogen content, ranks in descending order from the co-impregnation method, followed by the citrate complexation method, to the co-precipitation method

Ginkgolide B inhibits platelet and monocyte adhesion in TNFα-treated HUVECs under laminar shear stress

Abstract Background Endothelial cells are sensitive to changes in both blood components and mechanical stimuli. Endothelial cells may undergo phenotypic changes, such as changes in adhesion protein expression, under different shear stress conditions. Such changes may impact platelet and monocyte adhesion to endothelial cells. This phenomenon is linked to chronic vascular inflammation and the development of atherosclerosis. In the present study, we investigated the effects of ginkgolide B on platelet and monocyte adhesion to human umbilical vein endothelial cells (HUVECs) under different conditions of laminar shear stress. Methods Platelet and monocyte adhesion to endothelial cells was determined by the Bioflux 1000. HUVECs were incubated with ginkgolide B or aspirin for 12 h, and then TNFα was added for 2 h to induce the inflammatory response under conditions of 1 and 9 dyn/cm2 laminar shear stress. The protein expression was analyzed by Western blot. Results The number of platelets that adhered was greater under conditions of 1 dyn/cm2 than under conditions of 9 dyn/cm2 of laminar shear stress (74.8 ± 19.2 and 59.5 ± 15.1, respectively). Ginkgolide B reduced the tumor necrosis factor α (TNFα)-induced increase in platelet and monocyte adhesion to HUVECs at 1 and 9 dyn/cm2 of laminar shear stress. In TNFα-treated HUVECs, the number of monocytes that adhered was greater under conditions of 1 dyn/cm2 of laminar shear stress compared with 9 dyn/cm2 (29.1 ± 4.9 and 22.7 ± 3.7, respectively). Ginkgolide B inhibited the TNFα-induced expression of vascular cell adhesion molecule-1(VCAM-1), VE-cadherin, and Cx43 in HUVECs at 1 and 9 dyn/cm2. The expression of these proteins was not different between 1 and 9 dyn/cm2. Conclusions Ginkgolide B suppressed platelet and monocyte adhesion under different conditions of laminar shear stress. Moreover, ginkgolide B reduced VCAM-1, VE-cadherin and Cx43 expression in TNFα-treated HUVECs under laminar shear stress. This suggested that ginkgolide B might shed light on the treatment of inflammation in atherosclerosis

Resveratrol Confers Vascular Protection by Suppressing TLR4/Syk/NLRP3 Signaling in Oxidized Low-Density Lipoprotein-Activated Platelets

This study investigated the effect of resveratrol on Toll-like receptor 4- (TLR4-) mediated matrix metalloproteinase 3 (MMP3) and MMP9 expression in oxidized low-density lipoprotein- (ox-LDL-) activated platelets and the potential molecule mechanism. Human platelets were used in the present study. The results showed that resveratrol suppressed TLR4, MMP3, and MMP9 expression in ox-LDL-activated platelets. The TLR4 inhibitor CLI-095 also inhibited MMP3 and MMP9 expression and secretion in ox-LDL- and lipopolysaccharide- (LPS-) activated platelets. The combination of resveratrol and CLI-095 synergistically suppressed MMP3 and MMP9 expression in ox-LDL- and LPS-activated platelets. These findings suggest that the resveratrol-induced inhibition of MMP3 and MMP9 expression is linked to the suppression of TLR4 activation. Resveratrol also suppressed spleen tyrosine kinase (Syk) phosphorylation and nucleotide-binding domain leucine-rich repeat containing protein 3 (NLRP3) expression and IL-1β secretion in ox-LDL- and LPS-treated platelets. The coimmunoprecipitation results showed that resveratrol inhibited the binding of Syk and NLRP3. Finally, resveratrol reduced vascular senescence cells and the expression of TLR4, MMP3, and MMP9 and prevented alterations of vascular structure in 52-week-old mice. Our findings demonstrated that resveratrol decreased inflammatory protein expression and improved vascular structure in aged mice. Resveratrol inhibited the expression of TLR4 and secretion of MMP3, MMP9, and IL-1β. The mechanism of action of resveratrol appears to be associated with the inhibition of TLR4/Syk/NLRP3 activation in ox-LDL-activated platelets