Effects of dietary methionine on breast muscle growth, myogenic gene expression and IGF-I signaling in fast- and slow-growing broilers.

This study investigated the responses of fast- (FG) and slow- (SG) growing broilers to dietary methionine (Met) status. The broilers were subjected to low (LM, 0.38 and 0.28 g/100 g), adequate (AM, 0.51 and 0.42 g/100 g) and high (HM, 0.65 and 0.52 g/100 g) Met during 1-21 and 22-42 d, respectively. Compared with the LM diets, the AM and HM diets increased body weight gain only in the FG broilers. The HM diets increased breast muscle yield only in the FG broilers, although insulin-like growth factor-I (IGF-I) concentration was increased in both strains of broilers. The HM diets increased mRNA levels of myogenic regulatory factors (MRF4, Myf5) and myocyte enhancer factor 2 (MEF2A and MEF2B) in the FG broilers, and increased MEF2A and decreased myostatin mRNA level in the SG broilers. Extracellular signal-regulated kinase (ERK) phosphorylation of breast muscle was increased by the HM diets in both strains of broilers, but mechanistic target of rapamycin (mTOR) phosphorylation was increased by the AM and HM diets only in the FG broilers. These results reflect a strain difference in broiler growth and underlying mechanism in response to dietary Met.

The anti-dementia drug candidate, (-)-clausenamide, improves memory impairment through its multi-target effect.

Multi-target drugs, such as the cocktail therapy used for treating AIDS, often show stronger efficacy than single-target drugs in treating complicated diseases. This review will focus on clausenamide (clau), a small molecule compound originally isolated from the traditional Chinese herbal medicine, Clausenalansium. The finding of four chiral centers in clau molecules predicted the presence of 16 clau enantiomers, including (-)-clau and (+)-clau. All of the predicted enantiomers have been successfully synthesized via innovative chemical approaches, and pharmacological studies have demonstrated (-)-clau as a eutomer and (+)-clau as a distomer in improving cognitive function in both normal physiological and pathological conditions. Mechanistically, the nootropic effect of (-)-clau is mediated by its multi-target actions, which include mild elevation of intracellular Ca(2+) concentrations, modulation of the cholinergic system, regulation of synaptic plasticity, and activation of cellular and molecular signaling pathways involved in learning and memory. Furthermore, (-)-clau suppresses the pathogenesis of Alzheimer's disease by inhibiting multiple etiological processes: (1) beta amyloid protein-induced intracellular Ca(2+) overload and apoptosis and (2) tau hyperphosphorylation and neurodegeneration. In conclusion, the nature of the multi-target actions of (-)-clau substantiates it as a promising chiral drug candidate for enhancing human cognition in normal conditions and treating memory impairment in neurodegenerative diseases.

Role of brain-derived neurotrophic factor and NF-kappaB in neuronal plasticity and survival: From genes to phenotype.

PURPOSE: Brain-derived neurotrophic factor (BDNF) is a member of the family of neurotrophins and promotes diverse effects in neurons including development, maintenance of function, synaptic plasticity, and survival in different animal models. We present advances in our understanding of the genomics of the BDNF gene (bdnf) and its regulation by calcium-activated transcription factors, including cAMP response element binding protein (CREB) and more recently, nuclear factor kappaB (NF-kappaB) and discuss these findings in the context of neuronal plasticity and survival. METHODS: We used amplified bdnf complementary DNAs (cDNAs) and genomic DNA templates for direct sequencing and sequence variant discovery, information mining of public databases, and conventional molecular and cellular biology approaches to screen bdnf for novel regulatory elements, alternatively spliced exons, and functional sequence variants. RESULTS: We discovered a candidate NF-kappaB site in promoter 3 of bdnf and showned that activation of N-methyl-D-aspartate (NMDA) inotropic glutamate receptors increased bdnf expression through an NF-kappaB-dependent pathway and extended the finding to show that NF-kappaB was required for NMDA neuroprotection in vitro. In addition, sequence analysis of bdnf cDNAs from different brain regions predicted at least three pre-pro-BDNF protein isoforms, two of which were previously unknown. Each isoform differs at the amino terminus and may have functional importance. CONCLUSIONS: Given the central role that BDNF plays in the developing and adult nervous system, understanding how BDNF is regulated and how it functions will enhance our knowledge of its diverse effects, which may lead to more effective treatments for neurodegenerative disorders and reveal the role of BDNF in complex phenotypes related to behavior.

A clinical and experimental study on the protective effects of jiangzhi tongmai fang on endothelial injury.

31 cases of atherosclerosis (AS) were treated with Jiang Zhi Tong Mai Fang ([symbol: see text], formula of JZTMF), and its effect was compared with 30 cases treated with lovastatin in the control group. Clinically, the JZTMF formula showed an effect of regulating blood lipids, and therefore it was antiatherosclerotic. The mechanism is, probably, restoration of the function of endothelial cells (EC) by increasing the synthesis of 6-keto-PGF1 alpha and decreasing the release of endothelin (ET) as evidenced in the experimental study.