Diapocynin treatment induces functional and structural improvements in an advanced disease state in the mdx mice.

Duchenne muscular dystrophy (DMD) is the most common muscular disorder affecting children. It affects nearly 1 male birth over 5000. Oxidative stress is a pervasive feature in the pathogenesis of DMD.

Identification of Natural Products Inhibiting SARS-CoV-2 by Targeting Viral Proteases: A Combined in Silico and in Vitro Approach.

In this study, an integrated in silico-in vitro approach was employed to discover natural products (NPs) active against SARS-CoV-2. The two SARS-CoV-2 viral proteases, i.e.

Targeting RNA structure in SMN2 reverses spinal muscular atrophy molecular phenotypes.

Modification of SMN2 exon 7 (E7) splicing is a validated therapeutic strategy against spinal muscular atrophy (SMA). However, a target-based approach to identify small-molecule E7 splicing modifiers has not been attempted, which could reveal novel therapies with improved mechanistic insight. Here, we chose as a target the stem-loop RNA structure TSL2, which overlaps with the 5' splicing site of E7.

The anticancer drug tamoxifen counteracts the pathology in a mouse model of duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a severe disorder characterized by progressive muscle wasting,respiratory and cardiac impairments, and premature death. No treatment exists so far, and the identification of active substances to fight DMD is urgently needed. We found that tamoxifen, a drug used to treat estrogen-dependent breast cancer, caused remarkable improvements of muscle force and of diaphragm and cardiac structure in the mdx(5Cv) mouse model of DMD.

Ca2+-independent phospholipase A2 enhances store-operated Ca2+ entry in dystrophic skeletal muscle fibers.

Duchenne muscular dystrophy is caused by deficiency of dystrophin and leads to progressive weakness. It has been proposed that the muscle degeneration occurring in this disease is caused by increased Ca2+ influx due to enhanced activity of cationic channels that are activated either by stretch of the plasma membrane (stretch-activated channels) or by Ca2+-store depletion (store-operated channels). Using both cytosolic Ca2+ measurements with Fura-2 and the manganese quench method, we show here that store-operated Ca2+ entry is greatly enhanced in dystrophic skeletal flexor digitorum brevis fibers isolated from mdx(5cv) mice, a mouse model of Duchenne muscular dystrophy.

Cyclosporin A generates superoxide in smooth muscle cells.

Cyclosporin A (CsA) generates superoxide in smooth muscle cells. Our earlier studies have demonstrated that the increase in the vasopressin type 1 receptor induced in vascular smooth muscle cells in the presence of CsA is probably due to superoxide (Krauskopf et al., J Biol Chem 278, 41685-41690, 2003).

Complementary DNA arrays identify CD63 tetraspanin and alpha3 integrin chain as differentially expressed in low and high metastatic human colon carcinoma cells.

Malignant tumor cell invasion is determinant for metastasis to occur. E2 and C5 colon carcinoma cells that were derived from the parental Lovo line and that differ experimentally in spontaneous metastatic ability have been monitored for gene expression by cDNA arrays. Among genes found differentially expressed, the CD63 tetraspanin, not previously recognized in colon cancer progression, and the alpha3 integrin chain were both up-regulated in low metastatic E2 cells and were analyzed for their functional role using adhesion, migration, and invasion assays.