Intracellular potassium under osmotic stress determines the dielectrophoresis cross-over frequency of murine myeloma cells in the MHz range.

Dielectrophoresis (DEP) has been widely studied for its potential as a biomarker-free method of sorting and characterizing cells based upon their dielectric properties. Most studies have employed voltage signals from ∼1 kHz to no higher than ∼30 MHz. Within this range a transition from negative to positive DEP can be observed at the cross-over frequency fx01 . The value of fx01 is determined by the conductivity of the suspending medium, as well as the size and shape of the cell and the dielectric properties (capacitance, conductivity) of its plasma membrane. In this work DEP measurements were performed up to 400 MHz, where the transition from positive to negative DEP can be observed at a higher cross-over frequency fx02 . SP2/O murine myeloma cells were suspended in buffer media of different osmolarities and measurements taken of cell volume, fx01 and fx02 . Potassium-binding benzofuran isophthalate (PBFI), a potassium-sensitive fluorophore, and flow cytometry was employed to monitor relative changes in intracellular potassium concentration. In agreement with theory, it was found that fx02 is independent of the cell parameters that control fx01 and is predominantly determined by intracellular conductivity. In particular, the value of fx02 is highly correlated to that of the intracellular potassium concentration.

A Clinical Perspective of the Multifaceted Mechanism of Metformin in Diabetes, Infections, Cognitive Dysfunction, and Cancer.

In type 2 diabetes, ecological and lifecourse factors may interact with the host microbiota to influence expression of his/her genomes causing perturbation of interconnecting biological pathways with diverse clinical course. Metformin is a plant-based or plant-derived medicinal product used for the treatment of type 2 diabetes for over 60 years and is an essential drug listed by the World Health Organization. By reducing mitochondrial oxidative phosphorylation and adenosine triphosphate (ATP) production, metformin increased AMP (adenosine monophosphate)-activated protein kinase (AMPK) activity and altered cellular redox state with reduced glucagon activity, endogenous glucose production, lipogenesis, and protein synthesis. Metformin modulated immune response by directly reducing neutrophil to lymphocyte ratio and improving the phagocytic function of immune cells. By increasing the relative abundance of mucin-producing and short-chain-fatty-acid-producing gut microbes, metformin further improved the host inflammatory and metabolic milieu. Experimentally, metformin promoted apoptosis and reduced proliferation of cancer cells by reducing their oxygen consumption and modulating the microenvironment. Both clinical and mechanistic studies support the pluripotent effects of metformin on reducing cardiovascular-renal events, infection, cancer, cognitive dysfunction, and all-cause death in type 2 diabetes, making this low-cost medication a fundamental therapy for individualization of other glucose-lowering drugs in type 2 diabetes. Further research into the effects of metformin on cognitive function, infection and cancer, especially in people without diabetes, will provide new insights into the therapeutic value of metformin in our pursuit of prevention and treatment of ageing-related as well as acute and chronic diseases beyond diabetes.