Enzymatic Fuel Cell-Based Self-Powered Homogeneous Immunosensing Platform via Target-Induced Glucose Release: An Appealing Alternative Strategy for Turn-On Melamine Assay

Enzymatic fuel cell (EFC)-based self-powered biosensors have attracted considerable attention because of their unique feature of no need for extra power sources during the entire detection process, which endows them with the merits of simplicity, rapidness, low cost, anti-interference, and ease of use. Herein, we proposed, for the first time, an EFC-based self-powered homogeneous immunosensing platform by integrating the target-induced biofuel release and bioconjugate immunoassay for ultrasensitive melamine (ME) detection. In this design, the biofuel, i.e., glucose molecules, was entrapped in the pores of positively charged mesoporous silica nanoparticles and capped by the biogate AuNPs-labeled anti-ME antibody (AuNPs-Ab). The presence of the target ME triggered the entrapped glucose release due to the removal of the biogate via immunoreaction, which resulted in the transfer of electrons produced by glucose oxidation at the bioanode to the biocathode, and thus, the open-circuit voltage of the EFC-based self-powered immunosensor dramatically increased, realizing the ultrasensitive turn-on assay for ME. The limit of detection for ME assay was down to 2.1 pM (S/N = 3), superior to those previously reported in the literature. Notably, real milk samples need no special sample pretreatment for the detection of ME because of the good anti-interference ability of EFC-based self-powered biosensors and the excellent selectivity of the homogeneous immunoassay. Therefore, this appealing self-powered homogeneous immunosensing platform holds great promise as a successful prototype of portable and on-site bioassay in the field of food safety

Identification of a Potent Inhibitor of CREB-Mediated Gene Transcription with Efficacious in Vivo Anticancer Activity

Recent studies have shown that nuclear transcription factor cyclic adenosine monophosphate response element binding protein (CREB) is overexpressed in many different types of cancers. Therefore, CREB has been pursued as a novel cancer therapeutic target. Naphthol AS-E and its closely related derivatives have been shown to inhibit CREB-mediated gene transcription and cancer cell growth. Previously, we identified naphthamide <b>3a</b> as a different chemotype to inhibit CREB’s transcription activity. In a continuing effort to discover more potent CREB inhibitors, a series of structural congeners of <b>3a</b> was designed and synthesized. Biological evaluations of these compounds uncovered compound <b>3i</b> (<b>666-15</b>) as a potent and selective inhibitor of CREB-mediated gene transcription (IC₅₀ = 0.081 ± 0.04 μM). <b>666-15</b> also potently inhibited cancer cell growth without harming normal cells. In an in vivo MDA-MB-468 xenograft model, <b>666-15</b> completely suppressed the tumor growth without overt toxicity. These results further support the potential of CREB as a valuable cancer drug target

Identification of a Potent Inhibitor of CREB-Mediated Gene Transcription with Efficacious in Vivo Anticancer Activity

Recent studies have shown that nuclear transcription factor cyclic adenosine monophosphate response element binding protein (CREB) is overexpressed in many different types of cancers. Therefore, CREB has been pursued as a novel cancer therapeutic target. Naphthol AS-E and its closely related derivatives have been shown to inhibit CREB-mediated gene transcription and cancer cell growth. Previously, we identified naphthamide <b>3a</b> as a different chemotype to inhibit CREB’s transcription activity. In a continuing effort to discover more potent CREB inhibitors, a series of structural congeners of <b>3a</b> was designed and synthesized. Biological evaluations of these compounds uncovered compound <b>3i</b> (<b>666-15</b>) as a potent and selective inhibitor of CREB-mediated gene transcription (IC₅₀ = 0.081 ± 0.04 μM). <b>666-15</b> also potently inhibited cancer cell growth without harming normal cells. In an in vivo MDA-MB-468 xenograft model, <b>666-15</b> completely suppressed the tumor growth without overt toxicity. These results further support the potential of CREB as a valuable cancer drug target