Voltage-gated sodium (Na_v) channels are essential for the rapid upstroke of action potentials and the propagation of electrical signals in nerves and muscles. Defects of Na_v channels are associated with a variety of channelopathies. More than 1000 disease-related mutations have been identified in Na_v channels, with Na_v1.1 and Na_v1.5 each harboring more than 400 mutations. Na_v channels represent major targets for a wide array of neurotoxins and drugs. Atomic structures of Na_v channels are required to understand their function and disease mechanisms. The recently determined atomic structure of the rabbit voltage-gated calcium (Ca_v) channel Ca_v1.1 provides a template for homology-based structural modeling of the evolutionarily related Na_v channels. In this Resource article, we summarized all the reported disease-related mutations in human Nav channels, generated a homologous model of human Na_v1.7, and structurally mapped disease-associated mutations. Before the determination of structures of human Na_v channels, the analysis presented here serves as the base framework for mechanistic investigation of Na_v channelopathies and for potential structure-based drug discovery.

Mesenchymal stem cells (MSCs) are progenitors of connective tissues, which have emerged as important tools for tissue engineering due to their differentiation potential along various cell types. In recent years, accumulating evidence has suggested that the regulation of mitochondria dynamics and function is essential for successful differentiation of MSCs. In this paper, we review and provide an integrated view on the role of mitochondria in MSC differentiation. The mitochondria are maintained at a relatively low activity level inMSCs, and upon induction,mtDNAcopy number, protein levels of respiratory enzymes, the oxygen consumption rate, mRNA levels of mitochondrial biogenesis- associated genes, and intracellular ATP content are increased. The regulated level of mitochondrial ROS is found not only to influence differentiation but also to contribute to the direction determination of differentiation. Understanding the roles ofmitochondrial dynamics during MSC differentiation will facilitate the optimization of differentiation protocols by adjusting biochemical properties, such as energy production or the redox status of stem cells, and ultimately, benefit the development of new pharmacologic strategies in regenerative medicine.

Obesity, which underlies various metabolic and cardiovascular diseases, is a growing public health challenge for which established therapies are inadequate. Given the current obesity epidemic, there is a pressing need for more novel therapeutic strategies that will help adult individuals to manage their weight. One promising therapeutic intervention for reducing obesity is to enhance energy expenditure. Investigations into human brown fat and the recently discovered beige/brite fat have galvanized intense research efforts during the past decade because of their pivotal roles in energy dissipation. In this review, we summarize the evolution of human brown adipose tissue (hBAT) research and discuss new in vivo methodologies for evaluating energy expenditure in patients. We highlight the differences between human and mouse BAT by integrating and comparing their cellular morphology, function, and gene expression profiles. Although great advances in hBAT biology have been achieved in the past decade, more cellular models are needed to acquire a better understanding of adipose-specific processes and molecular mechanisms. Thus, this review also describes the development of a human brown fat cell line, which could provide promising mechanistic insights into hBAT function, signal transduction, and development. Finally, we focus on the therapeutic potential and current limitations of hBAT as an anti-glycemic, anti-lipidemic, and weight loss-inducing ‘metabolic panacea’.

MTUS1 (microtubule-associated tumor suppressor 1) has been identified that can function as a tumor suppressor gene in many malignant tumors. However, the function and mechanisms underlying the regulation of MTUS1 are unclear. In the present study, we reported that miR-19a and miR-19b (miR-19a/b) promote proliferation and migration of lung cancer cells by targeting MTUS1. First, MTUS1 was proved to function as a tumor suppressor in lung cancer and was linked to cell proliferation and migration promotion. Second, an inverse correlation between miR-19a/b expression and MTUS1 mRNA/protein expression was noted in human lung cancer tissues. Third, MTUS1 was appraised as a direct target of miR-19a/b by bioinformatics analysis. Fourth, direct MTUS1 regulation by miR-19a/b in lung cancer cells was experimentally affirmed by cell transfection assay and luciferase reporter assay. Finally, miR-19a/b were shown to cooperatively repress MTUS1 expression and synergistically regulate MTUS1 expression to promote lung cancer cell proliferation and migration. In conclusion, our findings have provided the first clues regarding the roles of miR-19a/b, which appear to function as oncomirs in lung cancer by downregulating MTUS1.