HMGB1 release induced by liver ischemia involves Toll-like receptor 4–dependent reactive oxygen species production and calcium-mediated signaling

Ischemic tissues require mechanisms to alert the immune system of impending cell damage. The nuclear protein high-mobility group box 1 (HMGB1) can activate inflammatory pathways when released from ischemic cells. We elucidate the mechanism by which HMGB1, one of the key alarm molecules released during liver ischemia/reperfusion (I/R), is mobilized in response to hypoxia. HMGB1 release from cultured hepatocytes was found to be an active process regulated by reactive oxygen species (ROS). Optimal production of ROS and subsequent HMGB1 release by hypoxic hepatocytes required intact Toll-like receptor (TLR) 4 signaling. To elucidate the downstream signaling pathways involved in hypoxia-induced HMGB1 release from hepatocytes, we examined the role of calcium signaling in this process. HMGB1 release induced by oxidative stress was markedly reduced by inhibition of calcium/calmodulin-dependent kinases (CaMKs), a family of proteins involved in a wide range of calcium-linked signaling events. In addition, CaMK inhibition substantially decreased liver damage after I/R and resulted in accumulation of HMGB1 in the cytoplasm of hepatocytes. Collectively, these results demonstrate that hypoxia-induced HMGB1 release by hepatocytes is an active, regulated process that occurs through a mechanism promoted by TLR4-dependent ROS production and downstream CaMK-mediated signaling

Comparative mitochondrial proteomic, physiological, biochemical and ultrastructural profiling reveal factorsunderpinning salt tolerance in tetraploid black locust (Robinia pseudoacacia L.)

Background: Polyploidy is an important phenomenon in plants because of its roles in agricultural and forestry production as well as in plant tolerance to environmental stresses. Tetraploid black locust (Robinia pseudoacacia L.) is a polyploid plant and a pioneer tree species due to its wide ranging adaptability to adverse environments. To evaluate the ploidy-dependent differences in leaf mitochondria between diploid and tetraploid black locust under salinity stress, we conducted comparative proteomic, physiological, biochemical and ultrastructural profiling of mitochondria from leaves. Results: Mitochondrial proteomic analysis was performed with 2-DE and MALDI-TOF-MS, and the ultrastructure of leaf mitochondria was observed by transmission electron microscopy. According to 2-DE analysis, 66 proteins that responded to salinity stress significantly were identified from diploid and/or tetraploid plants and classified into 9 functional categories. Assays of physiological characters indicated that tetraploids were more tolerant to salinity stress than diploids. The mitochondrial ultrastructure of diploids was damaged more severely under salinity stress than that of tetraploids. Conclusions: Tetraploid black locust possessed more tolerance of, and ability to acclimate to, salinity stress than diploids, which may be attributable to the ability to maintain mitochondrial structure and to trigger different expression patterns of mitochondrial proteins during salinity stress.This study was supported by the Fundamental Research Funds for the Central Universities (No. 2572016EAJ4; 2572015DA03; 2572017AA23), the National Natural Science Foundation of China (31170568)

PLGA-based drug delivery system for combined therapy of cancer: research progress

In recent years, PLGA micro/nano particle drug delivery systems has been widely used in cancer treatment. According to the unique properties of PLGA, carriers of various structures are designed to keep the function of drugs or bioactive substances, ensure the effective load of molecules and improve the bioavailability of drugs in diseased parts. PLGA is one of the earliest and most commonly used biodegradable materials. It is often used for functional modification with other polymers (such as polyethylene glycol and chitosan) or other molecules (such as aptamers and ligands) to deliver various small molecule drugs (such as DOX and DTX) and bioactive macromolecules (such as proteins and nucleic acids) to improve targeting, controlled release and therapeutic properties. In this paper, the preparation methods, physical and chemical properties and medical applications of PLGA micro/nano particles are discussed. We focused on the recent research progress of the PLGA-based drug carrier system in tumor combination therapy

Fabrication and Mechanical Behavior of Ex Situ Mg-Based Bulk Metallic Glass Matrix Composite Reinforced with Electroless Cu-Coated SiC Particles

Magnesium-based bulk metallic glass matrix composites (BMGMCs) have better plasticity than the corresponding bulk metallic glasses (BMGs); however, their strength and density are often compromised due to the fact that the effective reinforcement phase is mostly plastic heavy metal. For lightweight SiC-particle reinforced BMGMCs, interface wettability and the sharpness of the particles often reduce the strengthening effect. In this work, SiC particles were coated with a thin Cu coating by electroless plating, and added to Mg54Cu26.5Ag8.5Gd11 melt in an amount of 5 wt % to prepare a BMGMC. The microstructure of the interface, mechanical behavior and fracture morphology of the BMGMC were studied by scanning electron microscopy and quasi-static compression testing. The results showed that the Cu coating improved the wettability between SiC and the matrix alloy without obvious interfacial reactions, leading to the dispersion of SiC particles in the matrix. The addition of Cu-coated SiC particles improved the plastic deformation ability of Mg54Cu26.5Ag8.5Gd11 BMG, proving that electroless plating was an effective method for controlling the interface microstructure and mechanical behavior of BMGMCs

Targeted magnetic iron oxide nanoparticles for tumor imaging and therapy

Xiang-Hong Peng1,4, Ximei Qian2,4, Hui Mao3,4, Andrew Y Wang5, Zhuo (Georgia) Chen1,4, Shuming Nie2,4, Dong M Shin1,4*1Department of Medical Oncology/Hematology; 2Department of Biomedical Engineering; 3Department of Radiology; 4Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA; 5Ocean Nanotech, LLC, Fayetteville, AR, USAAbstract: Magnetic iron oxide (IO) nanoparticles with a long blood retention time, biodegradability and low toxicity have emerged as one of the primary nanomaterials for biomedical applications in vitro and in vivo. IO nanoparticles have a large surface area and can be engineered to provide a large number of functional groups for cross-linking to tumor-targeting ligands such as monoclonal antibodies, peptides, or small molecules for diagnostic imaging or delivery of therapeutic agents. IO nanoparticles possess unique paramagnetic properties, which generate significant susceptibility effects resulting in strong T2 and T*2 contrast, as well as T1 effects at very low concentrations for magnetic resonance imaging (MRI), which is widely used for clinical oncology imaging. We review recent advances in the development of targeted IO nanoparticles for tumor imaging and therapy.Keywords: iron oxide nanoparticles, tumor imaging, MRI, therap

Rapid Degradation of Azo Dyes by Melt-Spun Mg-Zn-Ca Metallic Glass in Artificial Seawater

Mg-Zn-Ca metallic glass (MG) is effective for degrading azo dyes; however, the related surface evolution and degradation mechanisms are little known. We comparatively investigated the initial surface corrosion morphologies of melt-spun Mg66Zn30Ca4 MG in deionized water and artificial seawater. It was found that the basic corrosion behavior of the MG was the same, except that the corrosion process was accelerated in seawater. The presence of NaCl obviously promotes the formation of nano-ZnO on the surface of ribbons, causing the rapid degradation of azo dyes due to the photocatalytic effect. The degradation efficiency when combined with 3.5 wt % NaCl was over 100 times higher than that without NaCl. This indicates that Mg-Zn-Ca MG ribbons are effective additives for the degradation of azo dyes in seawater

Improved Plasticity of Ti-Based Bulk Metallic Glass at Room Temperature by Electroless Thin Nickel Coating

By restricting the dilated deformation, surface modification can stimulate multiple shear banding and improve the plasticity of bulk metallic glasses (BMGs). Aimed at modifying the surface of BMGs by thin layers, a crystalline Ni coating with ultrafine grains was coated on the surface of a Ti-based BMG by electroless plating. With a thickness of about 10 μm, the prepared thin coating could effectively limit the fast propagation of primary shear bands and stimulate the nucleation of multiple shear bands. As a result, the compression plasticity of the coated Ti-based BMG was improved to about 3.7% from near 0% of the non-coated BMG. Except for a small amount of Ni coating was adhered to the BMG substrate after fracture, most of the coatings were peeled off from the surface. It can be attributed to the abnormal growth of some coarse grains/particles in local region of the coating, which induces a large tensile stress at the interface between the coating and the BMG substrate. It is suggested that, for electroless nickel plating, improving the adhesive bonding strength between the coating and the substrate has a better geometric restriction effect than simply increasing the thickness of the coating