AIM: To study the effects of aminoguanidine (AG) and two L-arginine analogues N(omega)-nitro-L-arginine methyl ester (L-NAME) and N(omega)-nitro-L-arginine (L-NNA) on nitric oxide (NO) production induced by cytokines ...AIM: To study the effects of aminoguanidine (AG) and two L-arginine analogues N(omega)-nitro-L-arginine methyl ester (L-NAME) and N(omega)-nitro-L-arginine (L-NNA) on nitric oxide (NO) production induced by cytokines (TNF-alpha, IL-1 beta, and IFN-gamma) and bacterial lipopolysaccharide (LPS) mixture (CM) in the cultured rat hepatocytes, and examine their mechanisms action. METHODS: Rat hepatocytes were incubated with AG, L-NAME, L-NNA, Actinomycin D (ActD) and dexamethasone in a medium containing CM (LPS plus TNF-alpha, IL-1 beta, and IFN-gamma) for 24h. NO production in the cultured supernatant was measured with the Griess reaction. Intracellular cGMP level was detected with radioimmunoassy. RESULTS: NO production was markedly blocked by AG and L-NAME in a dose-dependent manner under inflammatory stimuli condition triggered by CM in vitro. The rate of the maximum inhibitory effects of L-NAME (38.9%) was less potent than that obtained with AG(53.7%, P 【 0.05). There was no significant difference between the inhibitory effects of AG and two L-arginine analogues on intracellular cGMP accumulation in rat cultured hepatocytes. Non-specific NOS expression inhibitor dexamethasone (DEX)and iNOS mRNA transcriptional inhibitor ActD also significantly inhibited CM-induced NO production. AG(0.1 mmol x L(-1)) and ActD (0.2 ng x L(-1)) were equipotent in decreasing NO production induced by inflammatory stimuli in vitro, and both effects were more potent than that induced by non-selectivity NOS activity inhibitor L-NAME (0.1 mmol x L(-1)) under similar stimuli conditions (P【0.01). CONCLUSION: AG is a potent selective inhibitor of inducible isoform of NOS,and the mechanism of action may be not only competitive inhibition in the substrate level, but also the gene expression level in rat hepatocytes.展开更多
Amniotes differ substantially in absolute and relative brain size after controlling for allometry,and numerous hypotheses have been proposed to explain brain size evolution.Brain size is thought to correlate with proc...Amniotes differ substantially in absolute and relative brain size after controlling for allometry,and numerous hypotheses have been proposed to explain brain size evolution.Brain size is thought to correlate with processing capacity and the brain’s ability to support complex manipulation such as nest-building skills.The increased complexity of nest structure is supposed to be a measure of an ability to manipulate nesting material into the required shape.The degree of nest-structure complexity is also supposed to be associated with body mass,partly because small species lose heat faster and delicate and insulated nests are more crucial for temperature control of eggs during incubation by small birds.Here,we conducted comparative analyses to test these hypotheses by investigating whether the complexity of species-typical nest structure can be explained by brain size and body mass(a covariate also to control for allometric effects on brain size)across 1353 bird species from 147 families.Consistent with these hypotheses,our results revealed that avian brain size increases as the complexity of the nest structure increases after controlling for a significant effect of body size,and also that a negative relationship exists between nest complexity and body mass.展开更多
基金Project supported by the National Natural Science Foundation of China,No.39770861.and JANSSEN Science Research Foundation.
文摘AIM: To study the effects of aminoguanidine (AG) and two L-arginine analogues N(omega)-nitro-L-arginine methyl ester (L-NAME) and N(omega)-nitro-L-arginine (L-NNA) on nitric oxide (NO) production induced by cytokines (TNF-alpha, IL-1 beta, and IFN-gamma) and bacterial lipopolysaccharide (LPS) mixture (CM) in the cultured rat hepatocytes, and examine their mechanisms action. METHODS: Rat hepatocytes were incubated with AG, L-NAME, L-NNA, Actinomycin D (ActD) and dexamethasone in a medium containing CM (LPS plus TNF-alpha, IL-1 beta, and IFN-gamma) for 24h. NO production in the cultured supernatant was measured with the Griess reaction. Intracellular cGMP level was detected with radioimmunoassy. RESULTS: NO production was markedly blocked by AG and L-NAME in a dose-dependent manner under inflammatory stimuli condition triggered by CM in vitro. The rate of the maximum inhibitory effects of L-NAME (38.9%) was less potent than that obtained with AG(53.7%, P 【 0.05). There was no significant difference between the inhibitory effects of AG and two L-arginine analogues on intracellular cGMP accumulation in rat cultured hepatocytes. Non-specific NOS expression inhibitor dexamethasone (DEX)and iNOS mRNA transcriptional inhibitor ActD also significantly inhibited CM-induced NO production. AG(0.1 mmol x L(-1)) and ActD (0.2 ng x L(-1)) were equipotent in decreasing NO production induced by inflammatory stimuli in vitro, and both effects were more potent than that induced by non-selectivity NOS activity inhibitor L-NAME (0.1 mmol x L(-1)) under similar stimuli conditions (P【0.01). CONCLUSION: AG is a potent selective inhibitor of inducible isoform of NOS,and the mechanism of action may be not only competitive inhibition in the substrate level, but also the gene expression level in rat hepatocytes.
基金Financial support was provided by the National Natural Science Foundation of China(Grants 32211530420 and 32170481).
文摘Amniotes differ substantially in absolute and relative brain size after controlling for allometry,and numerous hypotheses have been proposed to explain brain size evolution.Brain size is thought to correlate with processing capacity and the brain’s ability to support complex manipulation such as nest-building skills.The increased complexity of nest structure is supposed to be a measure of an ability to manipulate nesting material into the required shape.The degree of nest-structure complexity is also supposed to be associated with body mass,partly because small species lose heat faster and delicate and insulated nests are more crucial for temperature control of eggs during incubation by small birds.Here,we conducted comparative analyses to test these hypotheses by investigating whether the complexity of species-typical nest structure can be explained by brain size and body mass(a covariate also to control for allometric effects on brain size)across 1353 bird species from 147 families.Consistent with these hypotheses,our results revealed that avian brain size increases as the complexity of the nest structure increases after controlling for a significant effect of body size,and also that a negative relationship exists between nest complexity and body mass.
