Controlled Decomposable Hydrogel Triggered with a Specific Enzyme.

In this study, superabsorbent polyelectrolyte hydrogels were synthesized by cross-linking a nondegradable poly (allylamine hydrochloride) (PAH) and a recombinant protein with a specific enzymatic cleavage site. The recombinant protein was produced by E. coli with the pET-32b(+) plasmid, which is featured with the thioredoxin (Trx) gene containing a thrombin recognition site and a T7/lac hybrid promoter for high expression of recombinant protein. The swelling test shows that the composite hydrogel still maintained a high swelling ratio to 900% when 15% recombinant protein was cross-linked with PAH. The degradation test shows that such a PAH composite hydrogel could be decomposed by the addition of specific enzyme thrombin, which might lead to new biomedical applications of hydrogels needed to be decomposable by specific time not determined by the time period.

A silver metal complex as a luminescent probe for enzymatic sensing of glucose in blood plasma and urine.

In this work, we present a facile preparation of a paper-based glucose assay for rapid, sensitive, and quantitative measurement of glucose in blood plasma and urine. Two copper phosphorescent complexes [Cu(2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline)(2,6-dimethylphenylisocyanide)2][B(C6H3(CF3)2)4] (Cu1) and [Cu(2,9-dimethyl-1,10-phenanthroline)(2,6-dimethylphenylisocyanide)2][B(C6H3(CF3)2)4] (Cu2) and a new silver congener [Ag(P3)CNAg(P3)][B(C6H3(CF3)2)4] (Ag3) (P3 = PPh2C6H4-PPh-C6H4PPh2 [bis(o-diphenylphosphinophenyl)phenylphosphine]) have been synthesized and their oxygen sensing abilities were investigated. The dimetallic phosphine-based Ag3 complex, having a high oxygen sensing ability, was employed as an efficient signal transducer in enzymatic reactions to recognize blood plasma glucose and urine glucose, which provided a wide linear response for a concentration range between 1.0 and 35 mM and a rapid response, with a limit of detection (LOD) of 0.09 mM for glucose. In practical application, this Ag3 paper-based device offers great analytical reliability and accuracy upon monitoring glucose concentrations in blood plasma.

Ag@Au nanoprism-metal organic framework-based paper for extending the glucose sensing range in human serum and urine.

In this work, we present a Ag@Au nanoprism-metal-organic framework-paper based glucose sensor for rapid, sensitive, single-use and quantitative glucose determination in human serum. To achieve painless measurement of glucose with a non-invasive detection methodology, this biosensor was further tested in human urine. In this approach, a new hybrid-Ag@Au nanoprism loaded in close proximity to micrometer sized coordination polymers as phosphorescent luminophores significantly enhanced the emission intensity due to metal-enhanced phosphorescence and worked as reaction sites to support more dissolved oxygen. Reports of enhanced phosphorescence intensity are relatively rare, especially at room temperature. The true enhancement factor of Ag@Au-phosphorescent metal-organic frameworks on paper was deduced to be 110-fold, making it a better optical type glucose meter. The results demonstrate the validity of the intensity enhancement effect of the excitation of the overlap of the emission band of a luminophore with the surface plasmon resonance band of Ag@Au nanoprisms. Ag@Au nanoprisms were used not only to improve the detection limit of glucose sensing but also to extend the glucose sensing range by enhancing the oxygen oxidation efficiency. The oxidation of glucose as glucose oxidase is accompanied by oxygen consumption, which increases the intensity of the phosphorescence emission. The turn-on type paper-based biosensor exhibits a rapid response (0.5 s), a low detection limit (0.038 mM), and a wide linear range (30 mM to 0.05 mM), as well as good anti-interference, long-term longevity and reproducibility. Finally, the biosensor was successfully applied to the determination of glucose in human serum and urine.

The dietary phytochemical 3,3'-diindolylmethane induces G2/M arrest and apoptosis in oral squamous cell carcinoma by modulating Akt-NF-κB, MAPK, and p53 signaling.

In light of the growing incidence of oral cancer in Taiwan, this study is aimed at investigating the antitumor activity of 3,3'-diindolylmethane (DIM), an active metabolite of the phytochemical indole-3-carbinol (I3C), in oral squamous cell carcinoma (OSCC). DIM exhibited substantially higher antiproliferative potency than I3C in three OSCC cell lines with IC(50) values in SCC2095, SCC9, and SCC15 cells, respectively, of 22 versus 168µM, 25 versus 176µM, and 29versus 300µM. Flow cytometric analysis and Comet assay indicated that DIM suppressed the viability of SCC2095 cells by inducing apoptosis and G2/M arrest. Western blot analysis of various signaling markers revealed the ability of DIM to target pathways mediated by Akt, mitogen-activated protein (MAP) kinases, nuclear factor (NF)-κB, and p53, of which the concerted action underlined its antitumor efficacy. The concomitant inactivation of Akt and MAP kinases in response to DIM facilitated the dephosphorylation of the proapoptotic protein Bad at Ser-136 and Ser-112, respectively. Through endoplasmic reticulum (ER) stress, DIM stimulated the activation of p53 via Ser-15 phosphorylation, leading to increased expression of the BH3-only proapoptotic Bcl-2 members Puma and Noxa. Together, these changes decreased the mitochondrial threshold for apoptosis. G2/M arrest might be attributable to the suppressive effect of DIM on the expression of cyclin B1 and cdc25c. As many downstream effectors of the Akt-NF-κB pathway, including glycogen synthase kinase 3ß, IκB kinase α, and cyclooxygenase-2, have been shown to promote oral tumorigenesis, the ability of DIM to inhibit this signaling axis underscores its chemopreventive potential in oral cancer.

Antitumor activity of a novel histone deacetylase inhibitor (S)-HDAC42 in oral squamous cell carcinoma.

The aberrant regulation of epigenetic systems including histone acetylation contributes to inappropriate gene expression in cancer cells. In this study, we investigated the antitumor effects of the novel histone deacetylase inhibitor (S)-HDAC42 in oral squamous cell carcinoma (OSCC) cells. The antiproliferative effect of (S)-HDAC42 was multifold higher than that of suberoylanilide hydroxamic acid in a panel of oral squamous carcinoma cell lines examined. (S)-HDAC42 mediated caspase-dependent apoptosis by targeting multiple signaling pathways relevant to cell cycle progression and survival. We demonstrated that (S)-HDAC42 downregulated the levels of phospho-Akt, cyclin D1, and cyclin-dependent kinase 6, accompanied by increased p27 and p21 expression. In addition, (S)-HDAC42 suppressed NF-κB signaling by blocking tumor necrosis factor-α-induced nuclear translocation, and activated reactive oxygen species generation. Finally, (S)-HDAC42 exhibited high potency in suppressing OSCC tumor growth in a Ca922 xenograft nude mouse model. Together, these findings underscore the translational value of (S)-HDAC42 in fostering new therapeutic strategies for OSCC.