BACKGROUND AND PURPOSE Current methods used to treat critical limb ischaemia (CLI) are hampered by a lack of effective strategies, therefore, therapeutic vasculogenesis may open up a new field for the treatment of CLI. In this study we investigated the ability of the DPP‐4 inhibitor, sitagliptin, originally used as a hypoglycaemic agent, to induce vasculogenesis in vivo. EXPERIMENTAL APPROACH Sitagliptin were administered daily to C57CL/B6 mice and eGFP transgenic mouse bone marrow‐transplanted ICR mice that had undergone hindlimb ischaemic surgery. Laser Doppler imaging and flow cytometry were used to evaluate the degree of neovasculogenesis and circulating levels of endothelial progenitor cells (EPCs) respectively. Cell surface markers of EPCs and endothelial NOS (eNOS) in vessels were studied. KEY RESULTS Sitagliptin elevated plasma glucagon‐like peptide‐1 (GLP‐1) levels in mice subjected to ischaemia, decreased plasma dipeptidyl peptidase‐4 (DPP‐4) concentration, and augmented ischaemia‐induced increases in stromal cell‐derived factor‐1 (SDF‐1) in a dose‐dependent manner. Blood flow in the ischaemic limb was significantly improved in mice treated with sitagliptin. Circulating levels of EPCs were also increased after sitagliptin treatment. Sitagliptin also enhanced the expression of CD 34 and eNOS in ischaemic muscle. In addition, sitagliptin promoted EPC mobilization and homing to ischaemic tissue in eGFP transgenic mouse bone marrow‐transplanted ICR mice. CONCLUSION AND IMPLICATIONS Circulating EPC levels and neovasculogenesis were augmented by the DPP‐4 inhibitor, sitagliptin and this effect was dependent on an eNOS‐related pathway in a mouse model of hindlimb ischaemia. The results indicate that oral administration of sitagliptin has therapeutic potential as an inducer of vasculogenesis.

Environmental stimuli-responsive nucleobase-functionalized supramolecular polymers, a combination of oligomeric polypropylene glycol segments as a thermosensitive element and hydrogen-bonded uracil as a photosensitive moiety, were successfully developed and undergo spontaneous self-assembly to form uniform nanosized micelles via self-complementary double hydrogen bonding interactions between the uracil moieties in an aqueous environment. These micelles exhibit unique properties such as dual thermo-and photoresponsiveness, controllable lower critical concentration solution temperature (LCST), photoreactivity, and morphological transformation, making them highly attractive for various applications. More importantly, phase transitions and morphological studies confirmed the LCST behavior, size, and shape of the micelles can be easily tuned by adjusting the concentration and duration of ultraviolet irradiation of samples in aqueous solution, indicating introduction of uracil molecules into a water-soluble polymer matrix may represent a promising approach toward development of multiple stimuliresponsive polymeric micelles whose self-assembly behavior can be manipulated. In view of the ease of fabrication, high biocompatibility, multifunctionality, and tailorable micellar properties, this newly developed supramolecular micelle may be a promising candidate nanocarrier for controlled drug delivery and bioimaging systems.

Through observing the enhanced autophagy expression in neurons soon after contusion injury and the inhibitive effect of methylprednisolone treatment, this study demonstrates the characteristics of autophagy expression after SCI and suggests that autophagic cell death may play a role in neuronal death after spinal cord trauma.

Self-assembled pH-responsive polymeric micelles, a combination of hydrophilic poly(ethylene glycol) segments and hydrogen bonding interactions within a biocompatible polyurethane substrate, can spontaneously self-assemble into highly controlled, nanosized micelles in aqueous solution. These newly developed micelles exhibit excellent pH-responsive behavior and biocompatibility, highly controlled drug (doxorubicin; DOX) release behavior, and high drug encapsulation stability in different aqueous environments, making the micelles highly attractive potential candidates for safer, more effective drug delivery in applications such as cancer chemotherapy. In addition, in vitro cell studies revealed the drug-loaded micelles possessed excellent drug entrapment stability and low cytotoxicity toward macrophages under normal physiological conditions (pH 7.4, 37 °C). When the pH of the culture media was reduced to 6.0 to mimic the acidic tumor microenvironment, the drug-loaded micelles triggered rapid release of DOX within the cells, which induced potent antiproliferative and cytotoxic effects in vitro. Importantly, fluorescent imaging and flow cytometric analyses confirmed the DOX-loaded micelles were efficiently delivered into the cytoplasm of the cells via endocytosis and then subsequently gradually translocated into the nucleus. Therefore, these multifunctional micelles could serve as delivery vehicles for precise, effective, controlled drug release to prevent accumulation and activation of tumor-promoting tumor-associated macrophages in cancer tissues. Thus, this unique system may offer a potential route toward the practical realization of next-generation pH-responsive therapeutic delivery systems.

The association between psoriasis and cardiovascular disease risk has been supported by recent epidemiological data. Patients with psoriasis have an increased adjusted relative risk for myocardial infarction. As such, the cardiovascular risk conferred by severe psoriasis may be comparable to what is seen with other well-established risk factors, such as diabetes mellitus. Previous studies demonstrated that low-density lipoprotein (LDL) plays critical roles during atherogenesis. It may be caused by the accumulation of macrophages and lipoprotein in the vessel wall. Oxidized LDL (ox-LDL) stimulates the expression of adhesion molecules, such as ICAM-1 and VCAM-1, on endothelial cells and increases the attachment of mononuclear cells and the endothelium. Even though previous evidence demonstrated that psoriasis patients have tortuous and dilated blood vessels in the dermis, which results in the leakage of ox-LDL, the leaked ox-LDL may increase the expression of adhesion molecules and cytokines, and disturb the static balance of osmosis. Therefore, exploration of the relationship between hyperlipidemia and psoriasis may be another novel treatment option for psoriasis and may represent the most promising strategy.