<i>In-Vitro</i>Inhibitory Effect of Methanol Extracts of Chinese Herbal Drugs on Supercoiling Activity of Bacterial DNA Gyrase

A large number of Chinese herbal drugs (CHDs) exhibit antibacterial activities both in vivo and in vitro, but until now little is known regarding their inhibitory mechanisms. Bacterial DNA gyrase is a proven target for antibacterial agents. Aim of this study was to investigate the in-vitro inhibitory effect of methanol extracts of CHDs against supercoiling activity of bacterial DNA gyrase. Fifteen CHDs were selected and extracted with methanol, respectively. Inhibitory effect of the extracts on DNA gyrase was tested using gel-based DNA supercoiling assay. Among fifteen CHDs tested, methanol extracts of Lonicerae Japonicae Flos (S2), Taraxaci Herba (S7), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (S8) demonstrated an obvious inhibitory effect against supercoiling activity of DNA gyrase, and the others were either less active or could not be determined with the present method. Moreover, it was likely that S7 and S8 inhibit gyrase in a concentration-dependent manner. In conclusion, DNA supercoiling assay is a promising method to study the inhibitory activity of CHDs on bacterial DNA gyrase. Some CHDs do have gyrase-inhibitory activity as proposed. Further investigations are needed to elucidate the inhibition mechanism of these CHDs on supercoiling activity of gyrase.

TRPV4 Regulates Soman-Induced Status Epilepticus and Secondary Brain Injury via NMDA Receptor and NLRP3 Inflammasome

Nerve agents are used in civil wars and terrorist attacks,posing a threat to public safety.Acute exposure to nerve agents such as soman(GD)causes serious brain damage,leading to death due to intense seizures induced by acetylcholinesterase inhibition and neuronal injury resulting from increased excitatory amino-acid levels and neuroinflammation.However,data on the anticonvulsant and neuroprotective efficacies of currently-used countermeasures are limited.Here,we evaluated the potential effects of transient receptor vanilloid 4(TRPV4)in the treatment of soman-induced status epilepticus(SE)and secondary brain injury.We demonstrated that TRPV4 expression was markedly up-regulated in rat hippocampus after soman-induced seizures.Administration of the TRPV4 antagonist GSK2193874 prior to soman exposure significantly decreased the mortality rate in rats and reduced SE intensity.TRPV4-knockout mice also showed lower incidence of seizures and higher survival rates than wild-type mice following soman exposure.Further in vivo and in vitro experiments demonstrated that blocking TRPV4 prevented NMDA receptor-mediated glutamate excitotoxicity.The protein levels of the NLRP3 inflammasome complex and its downstream cytokines IL-1βand IL-18 increased in soman-exposed rat hippocampus.However,TRPV4 inhibition or deletion markedly reversed the activation of the NLRP3 inflammasome pathway.In conclusion,our study suggests that the blockade of TRPV4 protects against soman exposure and reduces brain injury following SE by decreasing NMDA receptor-mediated excitotoxicity and NLRP3-mediated neuroinflammation.To our knowledge,this is the first study regarding the“dual-switch”function of TRPV4 in the treatment of soman intoxication.

Multi-walled carbon nanotubes as novel promoter of catalysts for certain hydrogenation and dehydrogenation reactions

From the chemical catalysis viewpoint,the excellent performance of CNTs in adsorption-activation of H2 and in promoting spillover of adsorbed H-species is very attractive,in addition to their nanosize channels,sp2-C constructed surfaces,and high thermal/electrical conductivity.This review examines some recent progresses of CNTs as a novel support or promoter of catalysts for certain hydrogenation or dehydrogenation reactions,e.g.,hydrogenation-conversion of syngas to yield alcohols and decomposition or steam-reforming of methanol to generate H2,mainly based on recent work carried out in our laboratory.