Inhibitory Effect of Resveratrol on LPS-induced Glomerular Mesangial Cells Proliferation and TGF-ß1 Expression via Sphingosine Kinase 1 Pathway.

OBJECTIVE: To elucidate the renoprotective effect of resveratrol (RSV) on sphingosine kinase 1 (SphK1) signaling pathway and expression of its downstream molecules including activator protein 1 (AP-1) and transformation growth factor-ß1 (TGF-ß1) in lipopolysaccharide (LPS)-induced glomerular mesangial cells (GMCs). METHODS: The rat GMCs line (HBZY-1) were cultured and randomly divided into 5 groups, including control, LPS (100 ng/mL), and 5, 10, 20 µmol/L RSV-treated groups. In addition, SphK1 inhibitor (SK-II) was used as positive control. GMCs were pretreated with RSV for 2 h and treated with LPS for another 24 h. GMCs proliferation was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The proteins expression of SphK1, p-c-Jun and TGF-ß1 in GMCs were detected by Western blot, and DNA-binding activity of AP-1 was performed by electrophoretic mobility shift assay (EMSA). The binding activity between RSV and SphK1 protein was detected by AutoDock Vina and visualized by Discovery Studio 2016. RESULTS: LPS could obviously stimulate GMCs proliferation, elevate SphK1, p-c-Jun and TGF-ß1 expression levels and increase the DNA-binding activity of AP-1 (P<0.05 or P<0.01), whereas these effects were significantly blocked by RSV pretreatment. It was also suggested that the effect of RSV was similar to SK-II (P>0.05). Moreover, RSV exhibited good binding affinity towards SphK1, with docking scores of -8.1 kcal/moL and formed hydrogen bonds with ASP-178 and LEU-268 in SphK1. CONCLUSION: RSV inhibited LPS-induced GMCs proliferation and TGF-ß1 expression, which may be independent of its hypoglycemic effect on preventing the development of mesangial cell fibrosis and closely related to the direct inhibition of SphK1 pathway.

Magnetic toroidal dipole response in individual all-dielectric nanodisk clusters.

Multipole electromagnetic resonances and their couplings are of crucial importance for both the fundamental understanding of light scattering by high-index all-dielectric nanostructures and lots of nanophotonic applications based on those nanostructures. Here, we show that magnetic dipole modes in a dielectric nanodisk cluster can easily form a magnetic toroidal dipole (MTD) mode. The cluster consists of five silicon nanodisks, where each nanodisk holds a magnetic dipole mode. These magnetic dipole modes can collectively couple with each other and form a MTD mode under suitable excitation. The MTD mode is confirmed by multipole expansion calculations and near field distributions, where two closed loops of magnetic field with opposite directions are seen. The response of the MTD is strong and comparable to that of a common electric dipole or magnetic dipole mode. It is also found that the MTD resonance is accompanied by an electric toroidal quadrupole mode in the cluster. The MTD mode is tunable by varying the geometries. We also fabricated silicon nanoparticle clusters and verified the MTD mode in the experiment. Our results illustrate the controllable excitation of strong high-order electromagnetic modes and these modes may open new opportunities for light manipulation at the nanoscale.

Strategic modulation of energy transfer in Au-TiO2-Pt nanodumbbells: plasmon-enhanced hydrogen evolution reaction.

Owing to the capacity of efficiently harvesting and converting incident energy, localized surface-plasmon resonance of noble metals was introduced into a metal-semiconductor design for promoting hydrogen evolution. In this study, a plasmonic nanodumbbell structure was employed to strategically modulate the energy transfer in the water reduction reaction. A maximum H2 evolution rate of 80 µmol g-1 h-1 was obtained in the Au-TiO2 nanodumbbells, and further improvement was achieved through surface modification with Pt nanoparticles functioning as active sites, leading to ∼4.3 times enhanced photocatalytic activity. Compared with similar nanostructures reported previously, the present superior photoactivity response is ascribed to the injection process of the energetic hot electrons generated from the excitation and decay of the longitudinal surface-plasmon resonance (LSPR) and transverse surface-plasmon resonance (TSPR) in the Au nanorods, which corresponds to the electric field distribution of the finite-difference-time-domain simulation. These intriguing results, originating from the positive synergistic effect of the plasmon and co-catalyst, demonstrated the mechanism of the plasmon-assisted photochemistry and provided a promising strategy for the rational design of novel plasmonic photocatalysts.

Efficient second harmonic generation in gold-silicon core-shell nanostructures.

We theoretically investigate the properties of second-harmonic generation (SHG) in gold-silicon core-shell nanostructures. We first study a concentric structure. This structure exhibits strong electric field enhancement in the silicon shell due to the combined toroidal dipole mode and electric dipole mode. Efficient SHG can be obtained and the SHG signal is about 5 times as strong as that of the individual Si shell. Further calculations show that the contribution from a surface nonlinear susceptibility at the inner surface of the silicon shell dominates the SHG signal of the core-shell structure. The SHG as a function of wavelength is considered and it shows a resonance behavior. The cases of nonconcentric core-shell structures have also been considered. The SHG is further enhanced in this kind of configuration and the SHG signal can reach about 10 times as strong as that of the concentric case. Our results reveal the strong modification of the SHGs in dielectric nanostructures by using the metal-dielectric hybrid configurations, and could find applications in nanoscale nonlinear devices.

Plasmonic nanoantenna-dielectric nanocavity hybrids for ultrahigh local electric field enhancement.

A dielectric nanostructure with a high refractive index can exhibit strong optical resonances with considerable electric field enhancement around the entire structure volume. Here we show theoretically that a dielectric structure with this feature can boost the local electric field of a small plasmonic nanoantenna placed nearby. We construct a hybrid system of a plasmonic nanoantenna and a dielectric nanocavity, where the nanocavity is a concentric disk-ring structure with a lossless material n = 3.3 and the nanoantenna is a gold nanorod dimer. The resonant electric field enhancement at the gap center of the antenna in the hybrid structure reaches more than one order of magnitude higher than that of the individual antenna. The dielectric structure plays two roles in the hybrid system, namely the amplified excitation field and an environment causing the redshift of the antenna resonance. The hybrid configuration is applicable to the cases with various geometries and different materials of the hybrid system. Our results can find applications in enhanced nanoscale light-matter interactions such as surface-enhanced Raman scattering, nonlinear optics, and plasmon-exciton couplings.

A quadratic correlation between long-term mean group size and group density in a cooperatively breeding passerine.

Both mean group size (MGS) and mean group density (MGD) are critical indices to characterize a population of cooperatively breeding birds. When a population reaches its carrying capacity, both long-term MGS and long-term MGD will remain relatively stable. However, there has been little study of how these two variables relate. The Masked laughingthrush Garrulax perspicillatus is a cooperatively breeding bird living in fragmented habitats. During 2010 and 2012-2016, we used song playback to observe and confirm the group sizes and territory ranges of the birds and the data of bird presence to determine habitat suitability. By grouping the nearest territories according to their geographical coordinates, we divided the whole study area into 12 subareas and the whole population into 12 subpopulations. Then, we calculated both MGS and MGD for different time durations for each subpopulation. Finally, using MGD as independent variable and MGS as the dependent variable, we explored the correlations between MGS and MGD by fitting quadratic functions and modeling quadratic regression. Both MGS and MGD were averaged for different time durations and were cross-related. Our results show that the MGS for more than 2 years significantly correlated with MGD for more than 3 years in a reverse parabolic shape, differing from that of short-term effects. Our findings suggest that long-term MGD is a better predictor of long-term habitat quality and that long-term MGS is determined by long-term habitat quality in Masked Laughingthrushes. Based on above findings, we can infer that: (1) Long-term habitat quality determines the long-term MGS, but it sets no prerequisite for the status and source of group members; (2) Long-term MGS in certain populations is adapted to the corresponding level of long-term habitat quality, it facilitates us to predict the helper effects on current or future survival or reproduction in different situations. These findings and inferences are both helpful for us to understand the evolution of cooperative breeding.

L-tetrahydropalamatine inhibits tumor necrosis factor-α-induced monocyte-endothelial cell adhesion through downregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 involving suppression of nuclear factor-κ B signaling pathway.

OBJECTIVE: To investigate whether I-tetrahydropalmatine (I-THP), an alkaloid mainly present in Corydalis family, could ameliorate early vascular inflammatory responses in atherosclerotic processes. METHODS: Fluorescently labeled monocytes were co-incubated with human umbilical vein endothelial cells (HUVECs), which were pretreated with I-THP and then simulated with tumor necrosis factor (TNF)-α in absence of I-THP to determine if I-THP could reduce thecytokine-induced adhesion of monocytes to HUVECs. Then I-THP were further studied the underlying mechanisms through observing the transcriptional and translational level of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and the nuclear translocation of nuclear factor (NF)-κ B in HUVECs. RESULTS: L-THP could block TNF-α-induced adhesion of monocytes to HUVECs and could significantly inhibited the expression of ICAM-1 and VCAM-1 on cell surface by 31% and 36% at 30 µ mol/L. L-THP pretreatment could also markedly reduce transcriptional and translational level of VCAM-1 as well as mildly reduce the total protein and mRNA expression levels of ICAM-1. Furthermore, I-THP attenuated TNF-α-stimulated NF-κ B nuclear translocation. CONCLUSION: These results provide evidences supporting that I-THP could be a promising compound in the prevention and treatment of the early vascular inflammatory reaction in atherosclerosis by inhibiting monocyte adhesion to vascular endothelial cell through downregulating ICAM-1 and VCAM-1 in vascular endothelial cell based on suppressing NF-κ B.

Comparative study on saponin fractions from Panax notoginseng inhibiting inflammation-induced endothelial adhesion molecule expression and monocyte adhesion.

BACKGROUND: Panax notoginseng is commonly used for the treatment of cardiovascular diseases in China. The present study investigates the effects of three different saponin fractions (ie total saponins, PNS; protopanaxadiol-type saponin, PDS; and protopanaxatriol-type saponin, PTS) and two major individual ingredients (ie ginsenoside Rg1 and Rb1) from P. notoginseng on the endothelial inflammatory response in vitro and in vivo. METHODS: Recombinant human tumor necrosis factor-α (TNF-α) was added to the culture medium of human coronary artery endothelial cells (HCAECs) to induce an inflammatory response. A cell adhesion assay was used to determine the effect of the P. notoginseng saponin fractions on endothelial-monocyte interaction. The cell adhesion molecule (CAMs) expression, including ICAM-1 and VCAM-1, in the protein level on the surface of endothelial cells were measured by cellular ELISA. CAMs expression in mRNA level was also assayed by qRT-PCR in the HCAECs and the aorta of rat fed with high cholesterol diet (HCD). Western blotting was used to detect effect of the saponin fractions on CAMs protein expression in HCAECs. In addition, nuclear translocation of p65, a surrogate marker for NF-κB activation, was measured by immunostaining. RESULTS: Three saponin fractions and two individual ginsenosides exhibited the inhibitory effects on monocyte adhesion on TNF-α-activated HCAECs and expression of ICAM-1 and VCAM-1 at both mRNA and protein levels in vitro. The saponin fractions exhibited a similar trend of the inhibitory effects on the mRNA expression of CAMs in the aorta of HCD-fed rat in vivo. These inhibitory effect of saponin fractions maybe attribute partially to the suppression of the TNF-α-induced NF-κB activation. CONCLUSION: Our data demonstrate that saponin fractions (ie PNS, PDS and PTS) and major individual ginsenosides (ie Rg1 and Rb1) have potential anti-atherogenic effects. Among the tested saponin fractions, PDS is the most potent saponin fraction against TNF-α-induced monocyte adhesion as well as the expression of adhesion molecules in vitro and in vivo.

Inhibition of TNF-α-mediated endothelial cell-monocyte cell adhesion and adhesion molecules expression by the resveratrol derivative, trans-3,5,4'-trimethoxystilbene.

Resveratrol (RSV) has been shown to have anti-inflammatory activity and to have a protective role against atherosclerosis. Here it is shown, for the first time, that its derivative trans-3,5,4'-trimethoxystilbene (TMS) may be a more potent anti-inflammatory agent than resveratrol. A comparative analysis of the inhibitory activities of related stilbenes, resveratrol, TMS and polydatin (PD), on monocyte adhesion to TNF-α-activated endothelial cells showed TMS to be the most effective, with PD being the least effective. RSV and its analogues inhibited, albeit differentially, the protein and mRNA expression levels of inducible cell adhesion molecules, ICAM-1 and VCAM-1, in cultured endothelial cells. The mechanism of the inhibitory effects of these stilbenes on endothelial cell-monocyte cell adhesion can be attributed mainly to inhibition of NF-κB pathway activation. The results demonstrate that all three investigated stilbene compounds, especially TMS, exhibit a potent inhibitory effect on inflammation-induced cell-cell adhesion, expression of adhesion molecules and activation of the NF-κB pathway.

Radix Astragali extract promotes angiogenesis involving vascular endothelial growth factor receptor-related phosphatidylinositol 3-kinase/Akt-dependent pathway in human endothelial cells.

Angiogenesis plays an important role in a wide range of physiological processes and many diseases are associated with dysregulation of angiogenesis. Radix Astragali, commonly used in traditional Chinese medicine, is a potential candidate for treating such diseases. However, the biological effects of Radix Astragali on angiogenesis and its underlying mechanisms are yet to be elucidated fully. This study describes the angiogenic effects of Radix Astragali extract (RAE) on human umbilical vein endothelial cells (HUVEC) in vitro. It was shown that RAE treatment stimulated HUVEC to proliferate. A significant increase in migration was observed in RAE-treated HUVEC using the wound healing migration assay. In addition, a significant increase in the number of branching points was observed during endothelial cell capillary formation after RAE treatment. It was shown that RAE enhances vascular endothelial growth factor (VEGF) mRNA expression, and that a specific blocker of VEGF receptor 2 (KDR/Flk) inhibited the RAE-induced HUVEC proliferation. In addition, a decrease in the RAE-induced HUVEC proliferation was observed after treatment with inhibitors of phosphatidylinositol 3-kinase (PI3K), Akt and endothelial nitric oxide synthase (eNOS). Taken together, these data suggest that RAE is a potent stimulator of angiogenesis and that its pro-angiogenic effects involve the VEGF-KDR/Flk and PI3K-Akt-eNOS pathways.

Berberine ameliorates renal injury in streptozotocin-induced diabetic rats by suppression of both oxidative stress and aldose reductase.

BACKGROUND: Berberine is one of the main constituents of Coptidis rhizoma (CR) and Cortex phellodendri. In this study, we investigated the beneficial effects of berberine on renal function and its possible mechanisms in rats with diabetic nephropathy (DN). METHODS: Male Wistar rats were divided into three groups: normal, diabetic model, and berberine treatment groups. Rats in the diabetic model and berberine treatment groups were induced to diabetes by intraperitonal injection with streptozotocin (STZ). Glomerular area, glomerular volume, fasting blood glucose (FBG), blood urea nitrogen (BUN), serum creatinine (Cr) and urine protein for 24 hours (UP24h) were measured using commercially available kits. Meanwhile, the activity of superoxide dismutase (SOD), content of malondialdehyde (MDA) in serum, activity of aldose reductase (AR) and the expression of AR mRNA and protein in kidney were detected by different methods. RESULTS: The results showed that oral administration of berberine (200 mg x kg(-1) x d(-1)) significantly ameliorated the ratio of kidney weight to body weight. Glomerular area, glomerular volume, FBG, BUN, Cr and UP24h were significantly decreased in the berberine treatment group compared with the diabetic model group (P < 0.05). Berberine treatment significantly increased serum SOD activity and decreased the content of MDA compared with diabetic model group (P < 0.05). AR activity as well as the expression of AR mRNA and protein in the kidney was markedly decreased in the berberine treatment group compared with diabetic model group (P < 0.05). CONCLUSION: These results suggested that berberine could ameliorate renal dysfunction in DN rats through controlling blood glucose, reduction of oxidative stress and inhibition of the activation of the polyol pathway.