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Abstract: Florfenicol has been shown to possess anti-inflammatory activity. However, its possible use for asthma has not yet been studied. First we investigated the anti-inflammatory properties of florfenicol using mice asthma model. BALB/c mice were immunized and challenged by ovalbumin. Treatment with florfenicol caused a marked reduction in inflammatory cells and three Th2 type cytokines in the bronchoalveolar lavage fluids of mice. The levels of ovalbumin-specific IgE and airway hyperresponsiveness were significantly altered after treatment with florfenicol. Histological studies using H&E and AB-PAS staining demonstrate that florfenicol substantially inhibited ovalbumin-induced inflammatory cells infiltration in lung tissue and goblet cell hyperplasia in the airway. These results were similar to those obtained with dexamethasone treatment. We then investigated which signal transduction mechanisms could be implicated in florfenicol activity. Our results suggested that the protective effect of florfenicol was mediated by the inhibition of the p38 MAPK-mediated phosphorylation of GATA 3. [Copyright &y& Elsevier]

Abstract: CpG islands (CGIs) in human genomic DNA are GC-rich fragments whose aberrant methylation is associated with human disease development. In the current study, methylation-sensitive mirror orientation selection (MS–MOS) was developed to efficiently isolate and enrich unmethylated CGIs from human genomic DNA. The unmethylated CGIs prepared by the MS–MOS procedure subsequently were used to construct a CGI library. Then the sequence characteristics of cloned inserts of the library were analyzed by bioinformatics tools, and the methylation status of CGI clones was analyzed by HpaII PCR. The results showed that the MS-MOS method could be used to isolate up to 0.001% of differentially existed unmethylated DNA fragments in two complex genomic DNA. In the CGI library, 34.1% of clones had insert sequences satisfying the minimal criteria for CGIs. Excluding duplicates, 22.0% of the 80,000 clones were unique CGI clones, representing 60% of all the predicted CGIs (about 29,000) in human genomic DNA, and most or all of the CGI clones were unmethylated in human normal cell DNA based on the HpaII PCR analysis results of randomly selected CGI clones. In conclusion, MS–MOS was an efficient way to isolate and enrich human genomic CGIs. The method has powerful potential application in the comprehensive identification of aberrantly methylated CGIs associated with human tumorigenesis to improve understanding of the epigenetic mechanisms involved. [Copyright &y& Elsevier]

The tripartite model of memory proposed the requirement of attentional switching when accessing different items in working memory [J. Exp. Psychol. Learn. Mem. Cogn. 27 (2001) 817]. This internal focus of attention is limited to just one item and the switching process is time-consuming [Mem. Cogn. 26 (1998) 263].In the current study, given a three-digit list stored in working memory, we found that it took longer to shift attention in the direction of “Upstream” than “Downstream”, and that each shift was a “single step” process. To investigate the neural basis of this type of attention switching, we performed a functional MRI study. The results revealed that at least three important brain areas are involved, including the left dorsal lateral prefrontal cortex, the cingulate gyrus, and the medial occipital cortex. These areas all showed greater activation in the attention shift condition compared to control conditions of no (or decreased) attention shift requirements. In addition, the hemodynamic activities in these areas are highly correlated, suggesting a strong functional connectivity between them. Taken together with evidence from several recent investigations, our results suggest that these areas each play an important and specific role in collaboratively supporting the function of attention shift in working memory. [Copyright &y& Elsevier]