Bone marrow-derived stem cells are self-renewing and multipotent adult stem cells that differentiate into several types of cells. Here, we investigated a unique combination of 4 differentiation-inducing factors (DIFs), including putrescine (Put), glucosamine (GlcN), nicotinamide, and BP-1-102, to develop a differentiation method for inducing mature insulin-producing cells (IPCs) and apply this method to bone marrow mononucleated cells (BMNCs) isolated from mice. BMNCs, primed with the 4 soluble DIFs, were differentiated into functional IPCs. BMNCs cultured under the defined conditions synergistically expressed multiple genes, including those for PDX1, NKX6.1, MAFA, NEUROG3, GLUT2, and insulin, related to pancreatic beta cell development and function. They produced insulin/C-peptide and PDX1, as assessed using immunofluorescence and flow cytometry. The induced cells secreted insulin in a glucose-responsive manner, similar to normal pancreatic beta cells. Grafting BMNC-derived IPCs under kidney capsules of mice with streptozotocin (STZ)-induced diabetes alleviated hyperglycemia by lowering blood glucose levels, enhancing glucose tolerance, and improving glucose-stimulated insulin secretion. Insulin- and PDX1-expressing cells were observed in the IPC-bearing graft sections of nephrectomized mice. Therefore, this study provides a simple protocol for BMNC differentiation, which can be a novel approach for cell-based therapy in diabetes mellitus.

Purpose: The feasibility and differential effects of two music therapy methods (interventions with preferred music vs. classical relaxation music) were done to examine the effects on agitation and anxiety in patients weaning off mechanical ventilation. Methods: This pilot study was conducted using a crossover design. Six patients listened to preferred music choices and classical relaxation music. Anxiety scores were measured using the Richmond Agitation Sedation Scale (RASS), State-Trait Anxiety Inventory (STAI), and visual analog scale (VAS). Results: Patients showed a significant decrease in agitation and anxiety after both the preferred and classical relaxation music interventions. The difference in the effects of preferred music and that of classical relaxation music was not significant. As for feasibility, patients exhibited a change in agitated behaviors after the music interventions by not trying to take off medical devices and quietly listening to the music, and by smiling and moving lips along with the lyrics while listening. Conclusion: Music interventions which centered on either patients' preferences or classical relaxation music to enhance relaxation, helped reduce agitation and anxiety during the mechanical ventilation weaning process.