Spironolactone Attenuates Bleomycin-Induced Pulmonary Injury Partially via Modulating Mononuclear Phagocyte Phenotype Switching in Circulating and Alveolar Compartments

Background

Recent experimental studies provide evidence indicating that manipulation of the mononuclear phagocyte phenotype could be a feasible approach to alter the severity and persistence of pulmonary injury and fibrosis. Mineralocorticoid receptor (MR) has been reported as a target to regulate macrophage polarization. The present work was designed to investigate the therapeutic potential of MR antagonism in bleomycin-induced acute lung injury and fibrosis.

Methodology/Principal Findings

We first demonstrated the expression of MR in magnetic bead-purified Ly6G-/CD11b+ circulating monocytes and in alveolar macrophages harvested in bronchoalveolar lavage fluid (BALF) from C57BL/6 mice. Then, a pharmacological intervention study using spironolactone (20mg/kg/day by oral gavage) revealed that MR antagonism led to decreased inflammatory cell infiltration, cytokine production (downregulated monocyte chemoattractant protein-1, transforming growth factor β1, and interleukin-1β at mRNA and protein levels) and collagen deposition (decreased lung total hydroxyproline content and collagen positive area by Masson’ trichrome staining) in bleomycin treated (2.5mg/kg, via oropharyngeal instillation) male C57BL/6 mice. Moreover, serial flow cytometry analysis in blood, BALF and enzymatically digested lung tissue, revealed that spironolactone could partially inhibit bleomycin-induced circulating Ly6C^hi monocyte expansion, and reduce alternative activation (F4/80+CD11c+CD206+) of mononuclear phagocyte in alveoli, whereas the phenotype of interstitial macrophage (F4/80+CD11c-) remained unaffected by spironolactone during investigation.

Conclusions/Significance

The present work provides the experimental evidence that spironolactone could attenuate bleomycin-induced acute pulmonary injury and fibrosis, partially via inhibition of MR-mediated circulating monocyte and alveolar macrophage phenotype switching.     

离子注入对微生物细胞的刻蚀与对DNA的损伤及修复

以耐辐射异常球菌为试材,以E. coli 为对照,用显微扫描电镜和3H-TdR标记,研究了离子注入对微生物细胞的刻蚀与对DNA的损伤及其修复。结果表明,注入离子对细胞存在着刻蚀损伤;中性蔗糖梯度密度离心沉降分析证明, 大剂量下离子注入可直接导致DNA损伤,并观察到在对应的存活率峰值注入剂量下,D. radiodurans修复损伤DNA的能力比E. coli 强,还证明了细胞经不同时间温育后,损伤的DNA分子得到了部分修复。 Abstract：　The direct action of N+implantationin on D. radioduransand E. coliwas investigated by SEM, and their cells were labeled with 3H-TdR, which were implanted by 20keV N+after incubation 18hours, then the DNA of lysed cells was subjected to the neutral sucrose gradient(5%～20%) ultra-centrifugation sedimentation analysis. The results showed that N+implantation exerted direct action on two kinds of microorganisms; the momentum transfer and energy deposition of implantation ions produced the direct etching damage on cells, and repair DNA efficiency of D.radiodurans was higher than that of E. coli. Meanwhile, the damaged DNA incomplete repairing was observed. When incubation was continued up to 6 hours, the rejoined DNA molecules broke again. The repair of damaged DNA could be inhibited by 200μg/ml chloramphenicol. This suggested that DNA damage was serious by ion implantation and damaged DNA repair of cells need continuously synthesizing repair enzyme.     

保护生物学概要

保护生物学的形成是对生物危机的反应和生物科学迅速发展的结果。它是应用科学解决由于人类活动干扰或其它因素引起的物种、群落和生态系统出现的问题的新学科。其”目的是提供保护生物多样性的原理和工具“,其基础科学和应用科学的综合性交叉学科。系统学、生态学、生物地理学和种群生态学的原理和方法是保护生物学重要的理论和实践基础。     

Interaction between GAMs and Mean Flow Shear During SMBI Injection into HL-2A Tokamak

Plasma Physics Reports - The interactions among geodesic acoustic modes (GAMs), mean flow, and mean flow shear were investigated using Langmuir probe arrays under periodic supersonic molecular beam...     

协同分布式实验2.0 (CDE 2.0):生态学野外研究新方法

全球野外实验网络是近年来兴起的生态学实验方法,产生了“协同分布式实验”(CDE)、“分布式协作实验”(DCE)的野外实验网络和英国生物学记录中心(BRC)的野外观察网络等具体方法,但均存在尺度小、周期短或数据偏差问题.野外实验网络的协议设计应秉持实验优于观察测量、数据数量优于数据质量和尺度优于操作的原则.综合上述方法,本研究提出利用公众科学(citizen science)获得大范围、多尺度和长周期的数据,采用环境因子作为协变量对公众参与者的实验数据集进行验证后,将其作为后验概率与作为主观概率的生态学家实验数据集进行比对,以完成数据有效性验证,克服公众参与者数据质量瑕疵,并提出了相应的统计学模型.讨论了生态学实验数据中应用先验概率、先验与后验概率的逻辑关系以及后验概率发现演化过程新关系的可能性.这种方法更符合统计学采样规范,并增加了大尺度时空的样本量.该方法有望为生态学研究所寻找的一般性理论提供方法支持,新方法可称之为“协同分布式实验2.0”(CDE 2.0).     

高粱抗蚜研究进展

高粱(Sorghum bicolour)是世界上最重要的粮食、饲料、酿造和能源作物之一, 也是C₄植物研究的模式植物。蚜虫是农业生产上的重要害虫, 几乎危害所有的栽培作物。危害高粱的蚜虫主要包括高粱蚜(Melanaphis sacchari)、麦二叉蚜(Schizaphis graminum)和玉米蚜(Rhopalosiphum maidis)。高粱的抗蚜资源尚不丰富且缺乏深入系统的研究。目前研究较多的是麦二叉蚜的抗性遗传方面, 已定位20个抗性QTLs, 单一QTL对抗性差异贡献率最高可达80.3%, 对高粱蚜和玉米蚜的研究尚需进一步加强。高粱的理化特性与其抗蚜性能相关, 故可与育种实践相结合。高粱和蚜虫(Acyrthosiphon pisum)的全基因组测序工作已经完成, 这将有助于蚜虫-植物间的相互作用关系及植物对蚜虫的抗性机制研究。目前已克隆到2个抗蚜基因, 且多个抗蚜基因(位点)已被定位在染色体上。该文重点综述了上述研究成果并对高粱抗蚜的研究前景进行了展望。     

Research progress on the effects of soil erosion on vegetation

The relationship between vegetation and soil erosion deserves attention due to its scientific importance and practical applications. A great deal of information is available about the mechanisms and benefits of vegetation in the control of soil erosion, but the effects of soil erosion on vegetation development and succession is poorly documented. Research shows that soil erosion is the most important driving force for the degradation of upland and mountain ecosystems. Soil erosion interferes with the process of plant community development and vegetation succession, commencing with seed formation and impacting throughout the whole growth phase and affecting seed availability, dispersal, germination and establishment, plant community structure and spatial distribution. There have been almost no studies on the effects of soil erosion on seed development and availability, of surface flows on seed movement and redistribution, and their influences on soil seed bank and on vegetation establishment and distribution. However, these effects may be the main cause of low vegetation cover in regions of high soil erosion activity and these issues need to be investigated. Moreover, soil erosion is not only a negative influence on vegetation succession and restoration, but also a driving force of plant adaptation and evolution. Consequently, we need to study the effects of soil erosion on ecological processes and on development and regulation of vegetation succession from the points of view of pedology and vegetation, plant and seed ecology, and to establish an integrated theory and technology for deriving practical solutions to soil erosion problems.     

趋磁细菌及磁小体在肿瘤治疗中的应用

提高抗肿瘤药物的靶向性是肿瘤治疗、降低药物副作用的重要手段。在肿瘤组织内部由于癌细胞的快速增殖致使其形成低氧区,低氧区会对多种肿瘤治疗方案产生耐受。趋磁细菌 (Magnetotactic bacteria, MTB) 是一类能在细胞内产生外包生物膜、纳米尺寸、单磁畴磁铁矿 (Fe3O4) 或硫铁矿 (Fe3S4) 晶体颗粒-磁小体的微生物的统称。在磁场的作用下,趋磁细菌可凭借鞭毛运动至厌氧区。趋磁细菌在动物体内毒性较低且生物相容性良好,其磁小体与人工合成的磁性纳米材料相比优势显著。文中在介绍趋磁细菌及其磁小体生物学特点、理化性能的基础上,综述了趋磁细菌作为载体偶联药物进入肿瘤内部,并通过感受低氧信号定位于肿瘤低氧区,以及趋磁细菌竞争肿瘤细胞铁源的研究进展,总结了磁小体运载化疗药物、抗体、DNA疫苗靶向结合肿瘤的研究进展,分析了趋磁细菌及磁小体肿瘤治疗中面临的问题,并对趋磁细菌和磁小体在肿瘤治疗中的应用进行了展望。     

人源乳酸菌对2型糖尿病小鼠的缓解效果

为考察人源乳酸菌(发酵乳杆菌Lactobacillus fermentum 11、305和植物乳杆菌Lactobacillus plantarum 22、25)对2型糖尿病的缓解效果,对2型糖尿病小鼠连续灌胃菌粉溶液12周.每周记录各组小鼠体重、进食量和血糖.实验结束前进行口服葡萄糖耐量试验和胰岛素抵抗试验.实验结束后...