Galectin-1 (Gal-1) is involved in several pathological activities associated with tumor progression and chemoresistance, however, the role and molecular mechanism of Gal-1 activity in hepatocellular carcinoma (HCC) epithelial–mesenchymal transition (EMT) and sorafenib resistance remain enigmatic. In the present study, forced Gal-1 expression promoted HCC progression and sorafenib resistance. Gal-1 elevated αvβ3-integrin expression, leading to AKT activation. Moreover, Gal-1 overexpression induced HCC cell EMT via PI3K/AKT cascade activation. Clinically, our data revealed that Gal-1 overexpression is correlated with poor HCC survival outcomes and sorafenib response. These data suggest that Gal-1 may be a potential therapeutic target for HCC and a biomarker for predicting response to sorafenib treatment.
Erythropoietin (EPO) is a well-known hormone that is clinically used for the treatment of anemia. Very recently, an increasing body of evidence showed that EPO could still regulate bioactivities of macrophages. However, the details about the immunomodulatory effect of EPO on macrophages are not fully delineated, particularly in the setting of renal damages. Therefore, in the present study, we determined whether EPO could exert an impact on the dynamics of macrophages in a well-established model of rhabdomyolysis-induced acute kidney injury and explored the potential mechanisms. EPO was found to ameliorate kidney injuries by reducing macrophages recruitment and promoting phenotype switch toward M2 macrophages in vivo. It was also confirmed that EPO could directly suppress pro-inflammatory responses of M1 macrophages and promote M2 marker expression in vitro. Data indicated the possible involvement of Jak2/STAT3/STAT6 pathway in the augmentation of EPO on M2 polarization. These results improved the understanding of the immunoregulatory capacity of EPO on macrophages, which might optimize the therapeutic modalities of EPO.
A continuous anionic living process for the fast synthesis of dendrimer-like star polymers is described. The process is based on the selective addition of sec-butyllithium (s-BuLi) toward 1,3-bis(1-phenylethenyl)benzene (MDDPE), which gives stoichiometric monoadduct in tetrahydrofuran (THF). The monoadduct, an anionic inimer-like molecule, is then used as the branching agent in the synthesis of dendrimer-like star polymers. Thus, α,ω-bifunctional polystyryllithium (G1.0), initiated by a difunctional anionic initiator, undergoes addition reaction with the monoadduct to form a tetrafunctional species, which is able to initiate the polymerization of styrene to form a four-arm star with terminal polystyryl anions (G2.0). Repeating addition/ polymerization in an alternate way leads to the formation of a dendrimer-like star polystyrene up to the fifth generation, G5.0. The process is performed in a continuous way without separation of the intermediate species. The synthetic procedure of dendritic polystyrene is greatly accelerated, e.g., G5.0 with 32 terminal groups being obtained within 12 h. Because the product is living, it is employed as a dendritic precursor to prepare dendrimer-like star block copolymers such as PS-b-PI, PS-b-PMMA, and dendrimer-like star polymer with a graft-on-graft periphery. The solution properties of the dendrimer-like star products, such as viscosity as a function of molecular weight and globular shape, are investigated using viscometry and laser light scattering. The morphology of the individual molecules is observed using AFM and TEM.
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