Highly Enhanced Cooperative Upconversion Luminescence through Energy Transfer Optimization and Quenching Protection

Upconversion luminescence nanomaterials have shown great potential in biological and physical applications because of their unique properties. However, limited research exists on the cooperative sensitization upconversion emission in Tb³⁺ ions over Er³⁺ ions and Tm³⁺ ions because of its low efficiency. Herein, by optimizing the doping ratio of sensitizer and activator to maximize the utilization of the photon energy and introducing the CaF₂ inert shell to shield sensitizer from quenchers, we synthesize ultrasmall NaYbF₄:Tb@CaF₂ nanoparticles with a significant enhancement (690-fold) in cooperative sensitization upconversion emission intensity, compared with the parent NaYbF₄:Tb. The lifetime of Tb³⁺ emission in NaYbF₄:Tb@CaF₂ nanoparticles is prolonged extensively to ∼3.5 ms. Furthermore, NaYbF₄:Tb@CaF₂ was applied in <i>in vitro</i> and <i>in vivo</i> bioimaging. The presented luminescence enhancement strategy provides cooperative sensitization upconversion with new opportunities for bioapplication

The Protective Effect of Esculentoside A on Experimental Acute Liver Injury in Mice

<div><p>Inflammatory response and oxidative stress are considered to play an important role in the development of acute liver injury induced by carbon tetrachloride (CCl₄) and galactosamine (GalN)/lipopolysaccharides (LPS). Esculentoside A (EsA), isolated from the Chinese herb phytolacca esculenta, has the effect of modulating immune response, cell proliferation and apoptosis as well as anti-inflammatory effects. The present study is to evaluate the protective effect of EsA on CCl₄ and GalN/LPS-induced acute liver injury. In vitro, CCK-8 assays showed that EsA had no cytotoxicity, while it significantly reduced levels of TNF-α and cell death rate challenged by CCl₄. Moreover, EsA treatment up-regulated PPAR-γ expression of LO2 cells and reduced levels of reactive oxygen species (ROS) challenged by CCl₄. In vivo, EsA prevented mice from CCl₄-induced liver histopathological damage. In addition, levels of AST and ALT were significantly decreased by EsA treatment. Furthermore, the mice treated with EsA had a lower level of TNF-α, Interleukin (IL)-1β and IL-6 in mRNA expression. EsA prevented MDA release and increased GSH-Px activity in liver tissues. Immunohistochemical staining showed that over-expression of F4/80 and CD11b were markedly inhibited by EsA. The western bolt results showed that EsA significantly inhibited CCl₄-induced phosphonated IkBalpha (P-IκB) and ERK. Furthermore, EsA treatment also alleviated GalN/LPS-induced acute liver injury on liver enzyme and histopathological damage. Unfortunately, our results exhibited that EsA had no effects on CCl₄-induced hepatocyte apoptosis which were showed by TUNEL staining and Bax, Caspase-3 and cleaved Caspase-3 expression. Our results proved that EsA treatment attenuated CCl₄ and GalN/LPS-induced acute liver injury in mice and its protective effects might be involved in inhibiting inflammatory response and oxidative stress, but not apoptosis with its underlying mechanism associated with PPAR-γ, NF-κB and ERK signal pathways.</p></div

Measurement of EsA cytotoxicity and effects of EsA on CCl₄-induced LO₂ cell injury <i>in</i><i>vitro</i>.

<p>The EsA cytotoxicity was measured using CCK-8 assays (A). Levels of TNF-α in LO2 culture mediums challenged by CCl₄ increased to approximately 4-fold and which was dramatically prevented by EsA treatment, and the concentration of 2.5 mg/L reduced the level of TNF-α most obviously (B). The cell death rate was observed by flow cytometric analysis (C). The values presented are the means ± standard error of the mean (n = 5). ^##P<0.01 versus the Control group. *P<0.05, **P<0.01 versus the Injury group.</p

The molecular structure of Esculentoside A (EsA).

<p>The molecular structure of Esculentoside A (EsA).</p

Effects of EsA on CCl₄-induced liver oxidative stress.

<p>EsA treatment significantly decreased levels of MDA (A) and increased the activity of GSH-Px (B) compared with the Injury group. The values presented are the means ± standard error of the mean (n = 6). ^##P<0.01 versus the Control group. *P<0.05 versus the Injury group.</p

Effects of EsA on CCl₄-induced liver inflammation.

<p>mRNA expression of TNF-a, IL-1β and IL-6 (A) and Immunohistochemical staining of F4/80 and CD11b cells (B) accumulating in liver tissues were determined at 12 hours post CCl₄-induced acute liver injury (Magnification, 200×). The values presented are the means ± standard error of the mean (n = 6). ^##P<0.01 versus the Control group. *P<0.05, **P<0.01 versus the Injury group.</p

The underlying mechanism of EsA against CCl₄-induced acute liver injury in mice.

<p>The activity of ERK (A) and IκB (B) were determined by western blot. Relative protein levels were quantified by densitometry and expressed as optical density ratio. The values presented are the means ± standard error of the mean (n = 6). ^## P<0.01 versus the Control group. **P<0.01 versus the Injury group.</p

Effects of EsA on cell apoptosis at 12 hours post-CCl₄ injection.

<p>Liver tissues sections were stained with TUNEL method (Magnification, ×200). There were no obvious difference for rates of positive TUNEL stained cells between the Injury and Injury+EsA groups (A). The activity of Bax, Caspase-3 and cleaved Caspase-3 were determined by western blot. Relative protein levels were quantified by densitometry and expressed as optical density ratio (B). The values presented are the means ± standard error of the mean (n = 6). ^#P<0.05, ^##P<0.01 versus the Control group.</p

EsA protected against CCl₄-induced histopathological damage and hepatic dysfunction.

<p>Hematoxylin and eosin staining (A Magnification, 200×) showed that livers in Injury group exhibited more ballooned hepatocytes than those in Control group and EsA group, and symptoms of those histopathological damage were significantly alleviated by EsA treatment (n = 6). Photographs of livers were taken 12 hours post-CCl₄ injection, livers in Injury group turned white (B). Levels of AST and ALT increased obviously after CCl₄ challenge. However, AST and ALT levels did not markedly increase in mice treated with EsA alone, and AST and ALT levels were significantly decreased with EsA treatment. (n = 6 C). The values presented are the means ± standard error of the mean. ^##P<0.01 versus the Control group. *P<0.05, **P<0.01 versus the Injury group.</p

Effects of EsA on CCl₄-induced LO₂ cell injury and PPAR-γ expression.

<p>The treatment effects of EsA and protein expression of PPAR-γ were measured using western blot (A). Levels of ROS in LO2 cells challenged by CCl₄ were shown (B Magnification, 200×). The mRNA expression of PPAR-γ was measured using quantitative real-time PCR (C). The values presented are the means ± standard error of the mean (n = 5). *P<0.05, **P<0.01.</p