Novel thermo and ion-responsive copolymers based on metallo-base pair directed host-guest complexation for highly selective recognition of Hg2+ in aqueous solution.

The development of materials with highly selective recognition towards Hg2+ is of great significance in environmental monitoring. Herein, a novel thermo-responsive copolymer with Hg2+ recognition property is prepared via thermally-initiated copolymerization of 5'-O-Acryloyl 5-methyl-uridine (APU) and N-isopropylacrylamide (NIPAM). The chemical structure and stimuli-sensitive properties of poly(N-isopropylacrylamide-co-5-methyl-uridine) (P(NIPAM-co-APU)) linear polymers and hydrogel are thoroughly investigated. At the supramolecular level, P(NIPAM-co-APU) linear polymers could respond to both temperature and Hg2+ stimuli with highly selective recognition towards Hg2+ over other 18 metal ion species (at least 5 fold difference) and common anions. Upon capturing Hg2+ by APU units as host metal receptors, the lower critical solution temperature (LCST) of P(NIPAM-co-APU, PNU-7 and PNU-11) linear polymers are significantly shifted more than 10 °C due to the formation of stable APU-Hg2+-APU directed host-guest complexes. Accordingly, at the macroscopic level, P(NIPAM-co-APU) hydrogel display selective and robust recognition of Hg2+ under optimum conditions, and its maximum Hg2+ uptake capacity was 33.1 mg g-1. This work provides a new option for Hg2+ recognition with high selectivity, which could be facilely integrated with other smart systems to achieve satisfactory detection of environmental Hg2+.

A novel chemosensor for sensitive and facile detection of strontium ions based on ion-imprinted hydrogels modified with guanosine derivatives.

A novel chemosensor is developed for the sensitive and facile detection of trace strontium ions (Sr2+) based on the ion-imprinted hydrogels. With Sr2+ as the templates, the ion-imprinted hydrogels are synthesized by copolymerizing the ion-responsive units 5'-O-acryloyl-2',3'-O-isopropylidene guanosine (APG) and the thermo-responsive units N-isopropylacrylamide (NIPAM). In the presence of Sr2+, APG units can self-assemble to form planar G-quartets via the complexation with Sr2+, which are introduced into the gel network during polymerization. Then Sr2+ templates can be removed by multiple repeated washing. When re-exposed to Sr2+, the relaxed G-quartets can recognize Sr2+, leading to the weakening of electrostatic repulsion between the four oxygen atoms in the G-quartets and inducing the shrinkage of the hydrogels. In this work, the Sr2+-imprinted chemosensors are designed as the grating systems for detecting trace Sr2+. Based on the array of hydrogel strings synthesized on a nano-scale, the smart grating systems thus constructed can convert and amplify the Sr2+ concentration signals to the easily-measurable optical signals. With the Sr2+-imprinted hydrogel gratings, trace Sr2+ (10-11 M) in an aqueous solution can be detected sensitively. Moreover, the proposed Sr2+-imprinted chemosensors can be integrated with other smart systems for developing various detectors with high performance.

Gekko-sulfated glycopeptide inhibits tumor angiogenesis by targeting basic fibroblast growth factor.

Basic fibroblast growth factor (bFGF) is a therapeutic target of anti-angiogenesis. Here, we report that a novel sulfated glycopeptide derived from Gekko swinhonis Guenther (GSPP), an anticancer drug in traditional Chinese medicine, inhibits tumor angiogenesis by targeting bFGF. GSPP significantly decreased the production of bFGF in hepatoma cells by suppressing early growth response-1. GSPP inhibited the release of bFGF from extracellular matrix by blocking heparanase enzymatic activity. Moreover, GSPP competitively inhibited bFGF binding to heparin/heparan sulfate via direct binding to bFGF. Importantly, GSPP abrogated the bFGF-stimulated proliferation and migration of endothelial cells, whereas it had no inhibitory effect on endothelial cells in the absence of bFGF. Further study revealed that GSPP prevented bFGF-induced neovascularization and inhibited tumor angiogenesis and tumor growth in a xenograft mouse model. These results demonstrate that GSPP inhibits tumor angiogenesis by blocking bFGF production, release from the extracellular matrix, and binding to its low affinity receptor, heparin/heparan sulfate.

The distinct role of guanine nucleotide exchange factor Vav1 in Bcl-2 transcription and apoptosis inhibition in Jurkat leukemia T cells.

AIM: To investigate a novel function of proto-oncogene Vav1 in the apoptosis of human leukemia Jurkat cells. METHODS: Jurkat cells, Jurkat-derived vav1-null cells (J.Vav1) and Vav1-reconstituted J.WT cells were treated with a Fas agonist antibody, IgM clone CH11. Apoptosis was determined using propidium iodide (PI) staining, Annexin-V staining, DNA fragmentation, cleavage of caspase 3/caspase 8, and poly (ADP-ribose) polymerase (PARP). Mitochondria transmembrane potential (ΔΨ(m)) was measured using DiOC(6)(3) staining. Transcription and expression of the Bcl-2 family of proteins were evaluated using semi-quantitative RT-PCR and Western blot, respectively. Bcl-2 promoter activity was analyzed using luciferase reporter assays. RESULTS: Cells lacking Vav1 were more sensitive to Fas-mediated apoptosis than Jurkat and J.WT cells. J.Vav1 cells lost mitochondria transmembrane potential (ΔΨ(m)) more rapidly upon Fas induction. These phenotypes could be rescued by re-expression of Vav1 in J.Vav1 cells. The expression of Vav1 increased the transcription of pro-survival Bcl-2. The guanine nucleotide exchange activity of Vav1 was required for enhancing Bcl-2 promoter activity, and the Vav1 downstream substrate, small GTPase Rac2, was likely involved in the control of Bcl-2 expression. CONCLUSION: Vav1 protects Jurkat cells from Fas-mediated apoptosis by promoting Bcl-2 transcription through its GEF activity.