Cellular targets of regulatory B cell-mediated suppression

Regulatory B cells (Bregs) are defined by their ability to restrain inflammatory responses both in vivo and in vitro. Interleukin 10 (IL-10) production by Bregs is thought to be central to their ability to regulate inflammation, largely due to IL-10s’ ability to suppress pro-inflammatory cytokine production by effector lymphocytes and to maintain the differentiation of regulatory T cells (Tregs). However, with an increase in available published data, it has become evident that Bregs utilize a number of suppressive mechanisms in order to alter the activation of a variety of different lymphocytes. Here, we summarize the multiplicity of cellular targets of Breg-mediated suppression and describe the mechanisms employed by Bregs to suppress chronic inflammatory responses.     

Carboxylesterase catalyzed 18O-labeling of carboxylic acid and its potential application in LC-MS/MS based quantification of drug metabolites

LC-MS quantification of drug metabolites is sometimes impeded by the availability of internal standards that often requires customized synthesis and/or extensive purification. Although isotopically labeled internal standards are considered ideal for LC-MS/MS based quantification, de novo synthesis using costly isotope-enriched starting materials makes it impractical for early stage of drug discovery. Therefore, quick access to these isotope-enriched compounds without chemical derivatization and purification will greatly facilitate LC-MS/MS based quantification. Herein, we report a novel ¹⁸O-labeling technique using metabolizing enzyme carboxylesterase (CES) and its potential application in metabolites quantification study. Substrates of CES typically undergo a two-step oxygen exchange with H₂¹⁸O in the presence of the enzyme, generating singly- and doubly-¹⁸O-labeled carboxylic acids; however, unexpected hydrolytic behavior was observed for three of the test compounds – indomethacin, piperacillin and clopidogrel. These unusual observations led to the discovery of several novel hydrolytic mechanisms. Finally, when used as internal standard for LC-MS/MS based quantification, these in situ labeled compounds generated accurate quantitation comparable to the conventional standard curve method. The preliminary results suggest that this method has potential to eliminate laborious chemical synthesis of isotope-labeled internal standards for carboxylic acid-containing compounds, and can be developed to facilitate quantitative analysis in early-stage drug discovery.     

Regulated expression of virulence gene mviN provides protective immunity and colonization control of Salmonella in poultry

Current live attenuated vaccines for control of Salmonella in poultry persist in the ceca and may persist in the environment. In this paper we report the construction and characterization of the vaccine efficacy of a Salmonella mutant strain with inducible mviN expression and rapid clearance from the host. The mutant was effective in oral immunization of the broiler chicken host against a virulent Salmonella oral challenge strain, having a mean 7 × 10⁶ CFU/g in the ceca of unvaccinated controls compared to a mean 2 × 10³ CFU/g in the ceca of vaccinated chickens at 4 weeks post-challenge (6 weeks of age). The mutant strain also demonstrated immunogenicity, reduced organ colonization, and rapid clearance in broiler chickens within 3 weeks of inoculation.     

CT动态增强鉴别肾上腺乏脂肪腺瘤与肾上腺结节样增生的价值

目的探讨CT动态增强对鉴别肾上腺乏脂肪腺瘤与肾上腺结节样增生的价值。方法回顾性分析经手术病理证实的12例肾上腺乏脂肪腺瘤和27例肾上腺结节样增生患者的病例资料,统计两组病例各期增强CT值,利用公式灌注值P=CT静脉期-CT平扫期、廓清值C=CT静脉期-CT延迟期、绝对廓清灌注指数APC=(C/P)×100%及相对廓清灌注指数RAPC=(C/CT静脉期)×100%得到相关参数,并通过绘制受试者工作特征曲线,鉴别两者的最佳价值。结果肾上腺乏脂肪腺瘤直径较结节样增生更大;肾上腺乏脂肪腺瘤病灶各期CT值均明显高于结节样增生,且两者灌注值P、廓清值C、APC及RAPC有明显的统计学差异。年龄、性别、高血压、病灶位置、对侧肾上腺萎缩及动脉期CT值对鉴别两者无显著意义。结论CT动态增强扫描有助于鉴别肾上腺乏脂肪腺瘤和肾上腺结节样增生。