Therapeutic potential of oleic acid supplementation in myotonic dystrophy muscle cell models.

Background: We recently reported that upregulation of Musashi 2 (MSI2) protein in the rare neuromuscular disease myotonic dystrophy type 1 contributes to the hyperactivation of the muscle catabolic processes autophagy and UPS through a reduction in miR-7 levels. Because oleic acid (OA) is a known allosteric regulator of MSI2 activity in the biogenesis of miR-7, here we sought to evaluate endogenous levels of this fatty acid and its therapeutic potential in rescuing cell differentiation phenotypes in vitro. In this work, four muscle cell lines derived from DM1 patients were treated with OA for 24 h, and autophagy and muscle differentiation parameters were analyzed.

Euler implicit time-discretization of multivariable sliding-mode controllers.

This paper aims to develop the Euler implicit time-discretization of multivariable sliding-mode controllers to solve the numerical chattering problem without modifying the continuous-time control law. To this end, a continuous-time multi-input plant under a multivariable sliding-mode control is studied, and it is shown that the implicit discretization of the continuous-time sliding-mode controller leads to a multivariable generalized equation with several set-valued terms which is not possible to be solved using the graphical interpretations. Subsequently, an algorithm is proposed to solve such a multivariable generalized equation required to synthesize the implicit sliding-mode control signal at each time step.

Cellular and Genomic Features of Muscle Differentiation from Isogenic Fibroblasts and Myoblasts.

The ability to recapitulate muscle differentiation in vitro enables the exploration of mechanisms underlying myogenesis and muscle diseases. However, obtaining myoblasts from patients with neuromuscular diseases or from healthy subjects poses ethical and procedural challenges that limit such investigations. An alternative consists in converting skin fibroblasts into myogenic cells by forcing the expression of the myogenic regulator MYOD.

Transformation of immunosuppressive mtKRAS tumors into immunostimulatory tumors by Nerofe and Doxorubicin.

Members of the rat sarcoma viral oncogene (RAS) subfamily KRAS are frequently mutated oncogenes in human cancers and have been identified in pancreatic ductal, colorectal, and lung adenocarcinomas. In this study, we show that a derivative of the hormone peptide Tumor Cell Apoptosis Factor (TCApF), Nerofe (dTCApFs), in combination with Doxorubicin (DOX) substantially reduces viability of tumor cells. It was observed that the combination of Nerofe and DOX downregulated KRAS signaling via miR217 upregulation, resulting in enhanced apoptosis of tumor cells.