T-5224, a selective inhibitor of c-Fos/activator protein-1, attenuates lipopolysaccharide-induced liver injury in mice

The effect of T-5224, a selective inhibitor of c-Fos/activator protein (AP)-1, on lipopolysaccharide (LPS) induced liver injury was examined in mice. Administration of LPS (10?mg?kg^?1, i.p.) markedly increased serum levels of tumor necrosis factor-alpha (TNFα), high mobility group box 1 (HMGB1), alanine aminotransferase/aspartate aminotransferase (ALT/AST), liver tissue levels of macrophage-inflammatory protein-1 alpha (MIP-1α) and monocyte chemoattractant protein-1 (MCP-1), as well as hepatic necrosis and inflammation, leading to 67?% lethality. Administration of T-5224 (300?mg?kg^?1, p.o.) after intraperitoneal injection of LPS imparted appreciable protection against acute elevations in serum levels of TNFα, HMGB1, ALT/AST as well as in liver tissue levels of MIP-1α and MCP-1, and reduced the lethality (27?%). These data indicate that T-5224 ameliorates liver injury and improves survival through decreasing production of proinflammatory cytokines and chemokines in endotoxemic mice.     

Mechanism of monolignol biotransformation by Rhus laccases in water-miscible organic solutions

Several important monolignols such as coniferyl alcohol were catalyzed using Rhus laccase (RL) from Rhus vernicifera in a water/acetone solution. The enzymatic mechanism is discussed in detail. Sites 6, β, and phenolic oxygen were the main active sites of phenylpropanoid compounds, which were first oxidized by the enzyme and then radicalized. RL was also responsible for lignin biosynthesis, especially in the early stage.     

Occlusion training increases muscular strength in division IA football players

The purpose of this study was to investigate the effectiveness of 4 weeks of low-intensity resistance training with blood-flow occlusion on upper and lower body muscular hypertrophy and muscular strength in National Collegiate Athletic Association Division IA football players. There were 32 subjects (average age 19.2 ± 1.8 years) who were randomized to an occlusion group or control group. The athletes performed 4 sets of bench press and squat in the following manner with or without occlusion: 30 repetitions of 20% predetermined 1 repetition maximum (1RM), followed by 3 sets of 20 repetitions at 20% 1RM. Each set was separated by 45 seconds. The training duration was 3 times per week, after the completion of regular off-season strength training. Data collected included health history, resting blood pressure, pretraining and posttraining bench press and squat 1RM, upper and lower chest girths, upper and lower arm girths, thigh girth, height, and body mass. The increases in bench press and squat 1RM (7.0 and 8.0%, respectively), upper and lower chest girths (3 and 3%, respectively), and left upper arm girth were significantly greater in the experiment group (p < 0.05). Occlusion training could provide additional benefits to traditional strength training to improve muscular hypertrophy and muscular strength in collegiate athletes.     

Identification of a novel substrate for TNFalpha-induced kinase NUAK2

TNFα has multiple important cellular functions both in normal cells and in tumor cells. To explore the role of TNFα, we identified NUAK family, SNF1-like kinase 2 (NUAK2), as a TNFα-induced kinase by gene chip analysis. NUAK2 is known to be induced by various cellular stresses and involved in cell mortality, however, its substrate has never been identified. We developed original protocol of de novo screening for kinase substrates using an in vitro kinase assay and high performance liquid chromatography (HPLC). Using this procedure, we identified myosin phosphatase target subunit 1 (MYPT1) as a specific substrate for NUAK2. MYPT1 was phosphorylated at another site(s) by NUAK2, other than known Rho-kinase phosphorylation sites (Thr696 or Thr853) responsible for inhibition of myosin phosphatase activity. These data suggests different phosphorylation and regulation of MYPT1 activity by NUAK2.     

Clinical and molecular diagnosis of a Costa Rican family with autosomal recessive myotonia congenita (Becker disease) carrying a new mutation in the CLCN1 gene

Myotonia congenita is a muscular disease characterized by myotonia, hypertrophy, and stiffness. It is inherited as either autosomal dominant or recessive known as Thomsen and Becker diseases, respectively. Here we confirm the clinical diagnosis of a family diagnosed with a myotonic condition many years ago and report a new mutation in the CLCN1 gene. The clinical diagnosis was established using ocular, cardiac, neurological and electrophysiological tests and the molecular diagnosis was done by PCR, SSCP and sequencing of the CLCN1 gene. The proband and the other affected individuals exhibited proximal and distal muscle weakness but no hypertrophy or muscular pain was found. The myotatic reflexes were lessened and sensibility was normal. Electrical and clinical myotonia was found only in the sufferers. Slit lamp and electrocardiogram tests were normal. Two affected probands presented diminution of the sensitive conduction velocities and prolonged sensory distal latencies. The clinical spectrum for this family is in agreement with a clinical diagnosis of Becker myotonia. This was confirmed by molecular diagnosis where a new disease-causing mutation (Q412P) was found in the family and absent in 200 unaffected chromosomes. No latent myotonia was found in this family; therefore the ability to cause this subclinical sign might be intrinsic to each mutation. Implications of the structure-function-genotype relationship for this and other mutations are discussed. Adequate clinical diagnosis of a neuromuscular disorder would allow focusing the molecular studies toward the confirmation of the initial diagnosis, leading to a proper clinical management, genetic counseling and improving in the quality of life of the patients and relatives.