趋磁性细菌与磁小体的研究与应用(综述)

1975年,美国生物学家Blakemore在试图分离海底泥样中的折叠螺旋体菌时,首次发现了自然界存在的一类奇特的微生物——趋磁性细菌(magnetotactic bacterium)。趋磁性细菌是一类能够沿着磁力线运动的特殊细菌,其体内含有对磁场具有敏感性的磁小体(magnetosomes),起了导向的作用,并借助于自身的鞭毛来运动。这     

趋磁细菌磁小体靶向输送pHSP70-shPLK1/阿霉素复合物治疗骨肉瘤北大核心

背景:在外加变化磁场作用下,磁小体可侵入肿瘤细胞,抑制其增殖。目的:研究趋磁细菌磁小体靶向输送pHSP70-shPLK1/阿霉素复合物治疗骨肉瘤的效果。方法:将人源骨肉瘤细胞株U2OS分4组培养,A组加入趋磁细菌磁小体载pHSP70-shPLK1/阿霉素复合物系统;B组加入趋磁细菌磁小体载pHSP-shNC/阿霉素复合物系统;C组加入趋磁细菌磁小体载pHSP70-shPLK1/阿霉素复合物系统,同时给予磁场干预;D组加入趋磁细菌磁小体载pHSP-shNC/阿霉素复合物系统,同时给予磁场干预;pHSP-shNC为pHSP70-shPLK1的空白对照。培养12,24,48,72h,观察骨肉瘤细胞对复合物的摄取率,流式细胞术观察细胞周期,RT-PCR法和Westernblot法检测细胞中PLK1mRNA和蛋白表达水平,MTT法检测细胞增殖,黏附实验和Transwell小室检测细胞黏附性和侵袭能力,凋亡试剂盒检测细胞凋亡率。结果与结论:(1)培养12,24h,D组摄取率最高;培养48,72h,B组摄取率最高;(2)A组、C组和D组G_2/M期比率逐渐降低,G_0/G_1期比率逐渐增加,C组G_2/M期比率各时间点最低,其次为D组,A组最高;B组G_2/M期比率逐渐增加;(3)培养12,24h,B组、D组PLK1表达高于A组、C组(P<0.05);培养48,72h,B组PLK1表达高于其余3组(P<0.05),D组高于A组、C组(P<0.05);(4)B组不同时间点的细胞增殖、黏附率及侵袭能力最高,细胞凋亡率最低;C组不同时间点的细胞增殖、黏附率及侵袭能力最低,细胞凋亡率最高;(5)结果表明,趋磁细菌磁小体靶向输送pHSP70-shPLK1/阿霉素复合物能够增强骨肉瘤细胞凋亡的发生,抑制其增殖和侵袭。     

使用磁性细菌粒子分离浓缩和检测癌胚抗原

磁性细菌为厌氧性螺旋状菌 ,呈革兰阴性 ,多发现于海底的淤泥之中 ;磁性细菌有沿着磁力线朝Ｎ极或Ｓ极泳动的走磁性 ,细菌体内约有 10～ 2 0颗粒径 (5 0～ 10 0ｎｍ)的磁性细菌粒子呈串状排列其中。电子线回折等的分析表明磁性细菌粒子的主成份为磁性Ｆｅ3Ｏ4 ,磁性细菌在含有铁离子的培养液中 ,常温常压状态下可以大量繁殖 ,生成的磁性细菌粒子成本低廉〔1,2〕。磁性细菌粒子表面全面覆盖着一层含有磷脂酰乙醇胺的脂质有机薄膜 ,与人工合成的磁石粒子相比磁性细菌粒子具有表面有机膜厚度均一且稳定牢固、有机膜表面抗体接种容易、形成的磁…     

基于超导量子干涉仪和磁性纳米粒子的肿瘤细胞早期检测新途径探究

磁性纳米粒子具有可以与所感兴趣的生物细胞相结合并增强其磁信号的特点。本研究利用医用脑磁仪中的高灵敏度磁检测系统,对基于纳米磁性粒子的肿瘤早期检测方法进行了探究。论文对4种可与肿瘤细胞结合的不同尺度磁性纳米粒子所产生的磁场进行了检测和仿真分析,并进行了初步的动物实验。结果显示,利用超导量子干涉仪(SQUID)构成的高精度磁检测系统可以对50 nm以上尺度的磁性粒子进行有效检测,该研究为开发基于SQUID和磁性纳米粒子的肿瘤细胞早期检测系统奠定了基础。     

磁性细菌的利用

前言磁性细菌是1975年发现的一种对地磁敏感、沿磁力线游动的细菌.磁性细菌在菌体内合成有约50～100nm的四氧化三铁(Fe_3O_4)磁性微粒子(磁性细菌粒子),该磁性细菌粒子在菌体内形成称之为磁性体的链.磁性细菌是一种微好氧性、对地磁敏感且沿磁力线游动的细菌,本文将以笔者在研究室所见为基础,对磁性细菌和磁性细菌粒子的应用等进行介绍.     

磁性细菌粒子的提取及医学应用

本文回顾了最近关于趋磁性细菌和磁性粒子方面的研究,并讨论了其在医学中的应用。生物磁性粒子是在动物和细菌中发现的。能感知方向、沿地磁场游动的趋磁性细菌,已从淡水和海水的沉淀物中分离出来。这些细菌微需氧地生长在污泥中,并含有固定大小的磁铁(Fe_3O_4)组成的磁性粒子。磁性粒子是稳定的单畴,500～1000大小,由10～20个粒子连接成行。酶和抗体与磁性细菌粒子结合,显示了高度的活性和重复使用性。用聚乙烯乙二醇使红细胞和趋磁性细     

纳米MnZn铁氧体微粒的磁热效应和细胞毒性

为了探讨SiO2包裹层对纳米磁性微粒的细胞毒性和磁热效应的影响,采用柠檬酸盐自燃烧法制备用于肿瘤磁热疗的纳米MnZn铁氧体微粒,应用ATP细胞活力测试和磁热量测定等方法,对其生物相容性和磁热效应进行测试。在60kHz交变磁场作用下,重量为10mg的包有SiO2的纳米磁性微粒在25min内可以使1mL去离子水温度升高26.5℃;未包裹SiO2的样品浸泡于37℃的生理模拟液（SBF溶液）中有微量的Zn^2＋、Fe^3＋、Mn^2＋离子溶出,但在剂量小于20mg时,其细胞毒性较小,而包裹了SiO2的样品则无论在剂量和时程上对细胞都没有影响。SiO2的包裹有利于提高纳米磁性微粒的生物相容性和细胞安全性,而且经过SiO2包裹的纳米磁性微粒的发热量仍能完全满足肿瘤磁热治疗的要求,其在肿瘤磁热治疗方面具有良好的应用前景。     

提高永磁材料磁性能在医学中的应用及展望

所谓磁性材料就是指可以用来制造磁功能元件的材料，它包括永（硬）磁材料、软磁材料、半硬磁材料、磁致伸缩材料、磁性薄膜、磁性微粉、磁性液体、磁致冷材料以及磁蓄冷材料等。最大磁能积（BH）max、矫顽力Hc、剩磁Br和饱和磁化强度Ms是磁性材料性能的最重要的性能指标．反应了磁性材料磁性能的高低及产生磁感应强度的大小。[第一段]     

三氧化二砷磁性微球的磁性能

目的:制备包裹三氧化二砷的磁性微球,分别测量磁性微球中三氧化二砷和四氧化三铁的含量,并分析其磁性能。讨论包裹三氧化二砷的磁性微球的磁靶向性效果和临床应用的可能性。 方法:采用化学共沉淀法制备四氧化三铁纳米铁磁粒子,采用w/o/w复乳法将纳米铁磁粒子和三氧化二砷包裹于聚D,L乳酸-羟基乙酸共聚物（PLGA）高分子材料中制备成磁性微球,利用全谱直读等离子体原子发射光谱仪测量磁性微球的载药量,分别测量纳米铁磁粒子和磁性微球的磁滞回线,并检验磁性微球的磁分离效果。 结果:纳米铁磁粒子和磁性微球的矫顽力和剩余磁化强度均接近零,但磁性微球的饱和磁化强度大大低于纳米铁磁粒子的饱和磁化强度。磁性微球的磁分离效果明显。 结论:合成的磁性微球外壳由PLGA高分子材料组成,纳米级四氧化三铁分散于PLGA中,壳内是三氧化二砷水溶液。磁性微球具有超顺磁性和磁靶向性。     

磁靶向定位灌注化疗膀胱癌磁性吡柔比星纳米粒的制备与评价

目的构建一种新型的磁靶向定位灌注化疗膀胱癌的吡柔比星纳米制剂,并探讨其磁靶向定位及抗膀胱癌细胞特性,为定位灌注化疗膀胱癌的临床应用提供帮助。方法通过N-N'-羰基二咪唑(CDI)交联剂将治疗膀胱癌的临床药物吡柔比星(pirarubicin,THP)连接在表面氨基化的四氧化三铁(Fe3O4)磁性纳米粒上,制备具有磁性的THP纳米制剂,并在体外考察其磁定位性能和对膀胱癌细胞的抑制作用。结果 THP成功地连接到了粒径40 nm左右的Fe3O4磁性纳米粒上,磁性药物制剂在不同p H值的缓冲液中药物在90%以上,并可在外界磁场作用下定位于靶向部位。对膀胱癌细胞可造成THP和Fe3O4双重抑制效果,抑制率高达58.44%。结论该纳米制剂可通过外界磁场定位于靶向部位,膀胱癌细胞抑制效果明显,为临床定位灌注化疗的应用奠定了基础。     

旋转磁场及静磁场对人肝癌细胞增殖的影响

目的：利用旋转磁场和静磁场对人肝癌细胞进行作用，探讨磁场对人肝癌细胞增殖的影响。材料和方法：将细胞株HepG2接种于96孔培养板，在37℃、5%CO2恒温培养箱培养24小时后放置于0．2T的旋转磁场（0－10Hz频率可调）和0．2T的静磁场中，作用一定时间后利用MTT法检测细胞增殖情况。结果：短时的旋转磁场作用和长时的静磁作用对HepG2细胞株的增殖无明显影响。     

Targeting to carcinoma cells with chitosan- and starch-coated magnetic nanoparticles for magnetic hyperthermia

The delivery of hyperthermic thermoseeds to a specific target site with minimal side effects is an important challenge in targeted hyperthermia, which employs magnetic method and functional polymers. An external magnetic field is used to control the site-specific targeting of the magnetic nanoparticles. Polymer-coated magnetic nanoparticles can confer a higher affinity to the biological cell membranes. In this study, uncoated, chitosan-coated, and starch-coated magnetic nanoparticles were synthesized for use as a hyperthermic thermoseed. Each sample was examined with respect to their applications to hyperthermia using XRD, VSM, and FTIR. In addition, the temperature changes under an alternating magnetic field were observed. As in vitro tests, the magnetic responsiveness of chitosan- and starch-coated magnetite was determined by a simple blood vessel model under various intensities of magnetic field. L929 normal cells and KB carcinoma cells were used to examine the cytotoxicity and affinity of each sample using the MTT method. The chitosan-coated magnetic nanoparticles generated a higher DeltaT of 23 degrees C under an AC magnetic field than the starch-coated magnetite, and the capturing rate of the particles was 96% under an external magnetic field of 0.4 T. The highest viability of L929 cells was 93.7%. Comparing the rate of KB cells capture with the rate of L929 cells capture, the rate of KB cells capture relatively increased with 10.8% in chitosan-coated magnetic nanoparticles. Hence, chitosan-coated magnetic nanoparticles are biocompatible and have a selective affinity to KB cells. The targeting of magnetic nanoparticles in hyperthermia was improved using a controlled magnetic field and a chitosan-coating. Therefore, chitosan-coated magnetic nanoparticles are expected to be promising materials for use in magnetic targeted hyperthermia.     

Discrepancy between brain magnetic fields elicited by pattern and luminance stimulations in the fovea: Adequate stimulus positions and a measure of discrepancy

Summary A conventional equivalent current dipole estimation provides one of the quantitative measures to evaluate the discrepancy between two single-dipole-like magnetic field patterns, though there is one problem; all stimulus positions in the visual field do not necessarily contribute to the generation of a single-dipole-like magnetic field. Another important problem occurs when the field pattern is complex and cannot be approximated by a dipole. This makes it difficult to evaluate the discrepancy between two magnetic field patterns by the dipole parameters. In this paper, we determined the stimulus positions adequate for generating single-dipole-like magnetic field patterns by evaluating the magnetic field's goodness-of-fit to the field generated by a single dipole. We propose to use a similarity (SIM) as a quantitative measure of the discrepancy between two complex magnetic field patterns. The SIM is defined as an angle between two magnetic field vectors. We evaluated the discrepancy between the 100 ms post-stimulus responses to pattern-reversal (Rv) stimulus, pattern-onset (Pat) stimulus, and luminance-onset (Lumi) stimulus. The following results were obtained: (1) Stimulation of some of the octants in the fovea, far from the vertical meridian, elicited a single-dipole-like magnetic field pattern at a latency of 100 ms, though stimulation of the central part of the fovea, and stimulation of the octants along the vertical meridian, did not elicit a single-dipole-like magnetic field pattern; (2) The discrepancy between responses was quantitatively evaluated by the SIM even if the field patterns were complex; (3) The SIM analysis showed that the discrepancy between the responses to the Rv and the Lumi stimuli, as well as that between the responses to the Pat and the Lumi stimuli, were greater than that between the responses to the Rv and the Pat stimuli.     

Induction of kinetochore-positive and kinetochore-negative micronuclei in CHO cells by ELF magnetic fields and/or X-rays

To test the genotoxic effects of extremely low frequency (ELF) magnetic fields, the induction of micronuclei by exposure to ELF magnetic fields and/or X-rays was investigated in cultured Chinese hamster ovary (CHO) cells, using the cytokinesis block method. Micronuclei derived from acentric fragments or from whole chromosomes were evaluated by immunofluorescent staining using anti-kinetochore antibodies from the serum of scleroderma (CREST syndrome) patients. A 60 Hz ELF magnetic field at 5 mT field strength was applied, either before or after 1 Gy X-ray irradiation or without additional X-ray irradiation. No statistically significant difference in the frequency of micronuclei in CHO cells was observed between a sham exposure (no exposure to an ELF magnetic field) and a 24 h ELF magnetic field exposure. Exposure to an ELF magnetic field for 24 h before X-ray irradiation or for 18 h after X-ray irradiation did not affect the frequency of X-ray-induced micronuclei. However, the number of kinetochore-positive micronuclei was significantly increased in the cells subjected to X-ray irradiation followed by ELF magnetic field exposure, but not in the cells treated with ELF magnetic field exposure before X-ray irradiation, compared with exposure to X-rays alone. The number of spontaneous kinetochore-positive and kinetochore-negative micronuclei was not affected by exposure to an ELF magnetic field alone. Our data suggest that exposure to an ELF magnetic field has no effect on the number of spontaneous and X-ray-induced micronuclei. However, ELF magnetic field exposure after but not before X-ray irradiation may somehow accelerate X-ray-induced lagging of whole chromosomes (or centric fragments) in CHO cells.     

Endophytic population of Pantoea agglomerans in citrus plants and development of a cloning vector for endophytes

Harmless bacteria inhabiting inner plant tissues are termed endophytes. Population fluctuations in the endophytic bacterium Pantoea agglomerans associated with two species of field cultured citrus plants were monitored over a two-year period. The results demonstrated that populations of P. agglomerans fluctuated in Citrus reticulata but not C. sinensis. A cryptic plasmid pPA3.0 (2.9 kb) was identified in 35 out of 44 endophytic isolates of P. agglomerans and was subsequently sequenced. The origins of replication were identified and nine out of 18 open reading frames (ORFs) revealed homology with described proteins. Notably, two ORFs were related to cellular transport systems and plasmid maintenance. Plasmid pPA3.0 was cloned and the gfp gene inserted to generate the pPAGFP vector. The vector was introduced into P. agglomerans isolates and revealed stability was dependent on the isolate genotype, ninety-percent stability values were reached after 60 hours of bacterial cultivation in most evaluated isolates. In order to definitively establish P. agglomerans as an endophyte, the non-transformed bacterium was reintroduced into in vitro cultivated seedlings and the density of inner tissue colonization in inoculated plants was estimated by bacterium re-isolation, while the tissue niches preferred by the bacterium were investigated by scanning electronic microscopy (SEM). Cells from P. agglomerans (strain ARB18) at similar densities were re-isolated from roots, stems and leaves and colonization of parenchyma and xylem tissues were observed. Data suggested that P. agglomerans is a ubiquitous citrus endophyte harboring cryptic plasmids. These characteristics suggest the potential to use the bacterium as a vehicle to introduce new genes in host plants via endophytic bacterial transformation.     

在缺氧条件下永磁磁场对胎鼠皮质神经元细胞生长、凋亡以及形态的影响

目的：在缺氧培养条件下,研究不同强度永磁磁场对胎鼠皮质神经元细胞生长、凋亡以及形态的影响。方法：将极面中心实测磁感强度为44．8mT、90．6mT、182．1mT的3组圆片磁源（简称为A组、B组、C组）,用有限元数值法计算出实际作用在细胞上的磁感强度范围,将以上3组不同强度磁场作用在胎鼠皮质神经元上,在缺氧条件下对细胞进行体外培养,实验分为对照组和加磁组,72h后分别检测细胞活性、细胞凋亡和细胞形态。结果：与对照组相比较,实验用各磁感强度加磁组细胞活性差异均无统计学意义;各磁感强度加磁组细胞凋亡率均低于对照组;在磁场作用下会降低细胞形态和细胞溶解。结论：在缺氧培养条件下,实验用各磁感强度组磁场对胎鼠皮质神经元细胞生长无显著影响,但会对细胞凋亡和细胞形态产生一定的影响。     

磁性阿霉素纳米微球在磁场中磁感应的发热研究

目的：制备一种在高频磁场中能感应发热的用于治疗肿瘤的阿霉素纳米微球，研究其在磁场中的热效应。材料与方法：用超声搅拌冷冻干燥的方法制备药物微球，电镜观察其形态及粒径估测。将其置于不同介质中于高频磁场中测其温度变化值。结果：磁性阿霉素微球为球囊状，平均粒径200nm左右，最小为150nm，最大为350nm，该微球在交变磁场中使介质升温。升温速度与平稳时的温度和微球的量，磁场强度成正比，介质流动性好，升温快。结论：可通过调节磁场强度和磁性阿霉素微球的量使周围温度达到所需值。     

Cardiac biomagnetic source estimation with a heart-torso model and a trained neural network.

The intensity of the cardiac sources for normal adult subjects was estimated from given magnetic field profiles with a trained neural network based on the relationship of the electrical activity of the heart to the cardiac magnetic fields. The input for training the neural network consisted of the magnetic field profiles above the torso during the heartbeat. The outputs were the dipole intensities which produced those magnetic field profiles. A back propagating algorithm with bias and momentum was utilized for training. The measured and simulated torso magnetic field profiles and magnetocardiograms were used for training the neural network. Estimation of the dipole intensities was performed for unknown magnetic field profiles with the trained neural network. The estimated cardiac dipole intensities were reasonably close to the true dipole intensities. These results show the feasibility of the estimation of cardiac dipole intensities with a trained neural network under a very restricted forward model of the cardiac magnetic fields. Generalization of the results to cover a large population base could be difficult because the activation isochrones are different from subject to subject.     

一定强度静磁场可促进许旺细胞快速分泌神经生长因子

背景：国内外对静磁场加载许旺细胞的研究较少,对其产生的生物学效应尚不清楚。目的：探索静磁场对许旺细胞分泌神经生长因子水平的影响。方法：将传代良好的许旺细胞随机分为3组,分别为0.05 mT静磁场组、0.1 mT静磁场组、空白对照组。从接种第2天即开始静磁场加载,每天曝磁12 h,空白对照组不进行静磁场加载。加载6 d后利用RT-PCR技术检测许旺细胞中神经生长因子mRNA的表达,ELISA技术检测许旺细胞分泌神经生长因子水平。结果与结论：静磁场组培养上清中神经生长因子mRNA的表达和分泌神经生长因子水平显著高于空白对照组(P < 0.05);0.1 mT静磁场组神经生长因子mRNA的表达和分泌神经生长因子水平虽高于0.05 mT静磁场组,但是差异无显著性意义(P >0.05)。结果表明一定强度的静磁场可以促进许旺细胞快速分泌神经生长因子。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

旋转磁场对烫伤大白鼠血液流变学及创面愈合的影响

本实验主要探讨烫伤大白鼠不同时间血液流变学指标的改变及旋转磁场对其的影响。结果显示，烫伤3小时与烫伤一周的全血表观粘度、血浆粘度、红细胞压积均比对照组高（P＜0．001）；而经旋转磁场处理一周的烫伤组，全血表现粘度、血浆粘度和红细胞压积均较烫伤3小时和烫伤一周的低（P＜0．01）。另外，采用旋磁治疗后，创面愈合较快，无感染。由此说明，旋转磁场不仅使血粘度降低，改善血循环，同时对促进创面愈合、水肿和渗出的吸收及炎症的消散有良好的作用[1]。