Myocardial ischemia, while causing cardiomyocyte injury, can activate innate protective processes, enhancing myocardial tolerance to ischemia. Such processes are present in not only the heart, but also remote organs. In this investigation, we demonstrated a cardioprotective process involving FGF21 from the liver and adipose tissue. In response to myocardial ischemia/reperfusion injury in the mouse, FGF21 was upregulated and released from the hepatic cells and adipocytes into the circulation and interacted with FGFR1 in cardiomyocytes under the mediation of the cell membrane protein β-Klotho, inducing FGFR1 phosphorylation. This action caused phosphorylation of the signaling molecules PI3K p85, Akt1, and BAD, thereby reducing caspase 3 activity, cell death, and myocardial infarction in association with improvement of myocardial function. These observations suggest that FGF21 is upregulated and released from the liver and adipose tissue in myocardial injury, contributing to myocardial protection by the mediation of the FGFR1/β-Klotho–PI3K–Akt1–BAD signaling network.

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Water pollution by heavy metal ions is a critical threat to public health. To remove the heavy metal pollutants from large waterbodies, we have synthesized a biocompatible, cost-effective, metal ion non-specific, and ethylenediaminetetraacetic acid (EDTA)-inspired polydentate hydrogel with exceptionally high adsorption capacity and reusability. The hydrogel was synthesized by the transamidation reaction between hydrolyzed polyacrylamide and branched polyethylenimine (BPEI). The mechanical strength of the synthesized hydrogel displayed an increasing trend with the wt % of the cross-linker (BPEI) and achieved a maximum storage modulus (G max ′) of 1093 Pa. Scanning electron microscopy revealed a porous network structure of the hydrogel (pore size: 30–70 μm), resulting in a very high swelling ratio of 5800%. The porous hydrogel manifested the maximum adsorption capacity of 482.2 mg/g when adsorbing from a mixture of metal ions (Cr3+, Cu2+, Zn2+, Cd2+, Hg2+, and Pb2+), higher than any EDTA-grafted material known to date. The high adsorption capacity of the hydrogel was attributed to the existence of numerous EDTA-mimicking coordinating functional groups, as confirmed by X-ray photoelectron spectroscopy. In addition, the hydrogel showed the self-healing property and preserved more than 85% adsorption efficiency even after five cycles of reuse. Furthermore, the hydrogels showed no or moderate toxicity toward mammalian cells.

Dual functional unimolecular micelles based on a pH-responsive amphiphilic star polymer β-CD-(PLA-b-PDMAEMA-b-PEtOxMA) 21 have been developed for the co-delivery of imiquimod and plasmid DNA to dendritic cells. The star polymer with well-defined triblock arms was synthesized by combining activator regenerated by electron-transfer atom-transfer radical polymerization with ring-opening polymerization. Dissipative particle dynamics simulation showed that core-mesophere-shell-type unimolecular micelles could be formed. Imiquimod-loaded micelles had a drug loading of 1.6 wt % and a larger average size (28 nm) than blank micelles (19 nm). The release of imiquimod in vitro was accelerated at the mildly acidic endolysosomal pH (5.0) in comparison to physiologic pH (7.4). Compared with blank micelles, a higher N:P ratio was required for imiquimod-loaded micelles to fully condense DNA into micelleplexes averaging 200-400 nm in size. In comparison to blank micelleplexes, imiquimod-loaded micelleplexes of the same N:P ratio displayed similar or slightly higher efficiency of gene transfection in a mouse dendritic cell line (DC2.4) without cytotoxicity. These results suggest that such pH-responsive unimolecular micelles formed by the well-defined amphiphilic star polymer may serve as promising nano-scale carriers for combined delivery of hydrophobic immunostimulatory drugs (such as imiquimod) and plasmid DNA with potential application in gene-based immunotherapy.

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