TW68, cryptochromes stabilizer, regulates fasting blood glucose levels in diabetic ob/ob and high fat-diet-induced obese mice.

Cryptochromes (CRYs), transcriptional repressors of the circadian clock in mammals, inhibit cAMP production when glucagon activates G-protein coupled receptors. Therefore, molecules that modulate CRYs have the potential to regulate gluconeogenesis. In this study, we discovered a new molecule called TW68 that interacts with the primary pockets of mammalian CRY1/2, leading to reduced ubiquitination levels and increased stability. In cell-based circadian rhythm assays using U2OS Bmal1-dLuc cells, TW68 extended the period length of the circadian rhythm. Additionally, TW68 decreased the transcriptional levels of two genes, Phosphoenolpyruvate carboxykinase 1 (PCK1) and Glucose-6-phosphatase (G6PC), which play crucial roles in glucose biosynthesis during glucagon-induced gluconeogenesis in HepG2 cells. Oral administration of TW68 in mice showed good tolerance, a good pharmacokinetic profile, and remarkable bioavailability. Finally, when administered to fasting diabetic animals from ob/ob and HFD-fed obese mice, TW68 reduced blood glucose levels by enhancing CRY stabilization and subsequently decreasing the transcriptional levels of Pck1 and G6pc. These findings collectively demonstrate the antidiabetic efficacy of TW68 in vivo, suggesting its therapeutic potential for controlling fasting glucose levels in the treatment of type 2 diabetes mellitus.

New biocompatible antibacterial wound dressing candidates; agar-locust bean gum and agar-salep films.

Agar has numerous applications in biomedical and biopharmaceutical fields in gel form. However the hard and tough nature of agar films and their vulnerability to microbial attacks prevent their usage in wound dressing applications. In this work, agar - locust bean gum (LBG) and agar - salep films were prepared for the first time to improve its physical, antimicrobial and cell viability properties. LBG and salep incorporated films resulted in higher antimicrobial and cell viability properties than agar films, which are very important in wound dressing applications. Agar - LBG films had higher water vapor permeabilities and were insoluble in water and in phosphate buffer solutions. Salep incorporation resulted in lower water vapor permeability and films were soluble in both media. All films were transparent, allowing good observability. With LBG and salep addition, lower tensile strength films were obtained and thicknesses of all films were appropriate for wound dressing applications. Due to their solubility, agar - salep films can be preferred especially for the cases where removal from the wound without damaging the tissue structure is a priority.

Biocompatible Quantum Funnels for Neural Photostimulation.

Neural photostimulation has high potential to understand the working principles of complex neural networks and develop novel therapeutic methods for neurological disorders. A key issue in the light-induced cell stimulation is the efficient conversion of light to bioelectrical stimuli. In photosynthetic systems developed in millions of years by nature, the absorbed energy by the photoabsorbers is transported via nonradiative energy transfer to the reaction centers. Inspired by these systems, neural interfaces based on biocompatible quantum funnels are developed that direct the photogenerated charge carriers toward the bionanojunction for effective photostimulation. Funnels are constructed with indium-based rainbow quantum dots that are assembled in a graded energy profile. Implementation of a quantum funnel enhances the generated photoelectrochemical current 215% per unit absorbance in comparison with ungraded energy profile in a wireless and free-standing mode and facilitates optical neuromodulation of a single cell. This study indicates that the control of charge transport at nanoscale can lead to unconventional and effective neural interfaces.