Interaction of major facilitator superfamily domain containing 2A with the blood-brain barrier

The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly understood.The major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier function.It plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain barrier.Furthermore,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain barrier.This paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier permeability.This comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to date.This will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic monitoring.In addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier leakage in various diseases and the research progress on cross-blood-brain barrier drug delivery are summarized.This review may contribute to the development of new approaches for the treatment of neurological diseases.

云南土壤宏基因组文库中替加环素耐药基因的筛选与分析

【背景】随着抗生素的广泛应用以及滥用,出现了多重耐药的"超级细菌",并且在临床上已出现对治疗"超级细菌"感染的最后一线抗生素——替加环素耐药的细菌。【目的】对土壤环境中存在的替加环素耐药基因进行筛选调查,探讨替加环素耐药机制,为临床抗生素治疗提供借鉴。【方法】利用功能宏基因组学技术对土壤宏基因组文库进行替加环素耐药阳性克隆的筛选和耐药亚克隆的构建,对构建成功的亚克隆进行测序和生物信息学分析探知其功能,同时进行最低抑菌浓度(Minimum Inhibitory Concentration,MIC)的测定。【结果】筛选得到一个四环素抗性Major Facilitator Superfamily(MFS)外排泵基因,携带该基因的菌株对四环素类抗生素均耐药,对替加环素和四环素的MIC值分别为16μg/mL和32μg/mL。当MFS外排泵抑制剂羰基氰化物间氯苯腙(CarbonylCyanide3-Chlorophenylhydrazone,CCCP)浓度为4μg/mL时可以抑制其对四环素类抗生素的外排作用。生物信息学结果表明该基因编码483个氨基酸,编码的蛋白质属于疏水稳定蛋白;其含有的14个跨膜区构成MFS外排泵蛋白典型的14次跨膜螺旋保守结构域;系统进化树分析表明其与其他替加环素耐药基因编码的蛋白质位于不同的分支上,相似性较低。【结论】利用功能宏基因组学技术筛选得到一个有替加环素抗性的MFS外排泵基因,编码的蛋白质属于14次跨膜螺旋MFS外排泵家族,为今后研究替加环素耐药机制提供参考。