试论磁场治疗恶性肿瘤中的三对矛盾凋亡与增殖免疫与肿瘤阻塞与供给

脉冲梯度磁场(峰值磁场0.2~2.0T,梯度10~100T.M-1,脉冲宽度20~200ms,重复频率0.16~1.34HZ)抑制鼠恶性肿瘤的细胞增殖和诱导细胞凋亡,提高宿主细胞免疫功能和抑制肿瘤生长,阻塞供给肿瘤生长的新生血管。虽然进一步的清晰的机理研究是非常需要的,但是上面的发现能够成为治疗恶性肿瘤的一种新方法。     

一定参数的磁场在不同生物层次上抑制恶性肿瘤生长

目的 :在不同生物层次上观测一定参数的磁场抑制恶性肿瘤生长。方法 :用脉冲梯度磁场 (峰值磁场 0 .6- 2 .0T ,磁场梯度 1 0 - 1 0 0T·M - 1 ,脉冲宽度 2 0 - 2 0 0ms,重复频率 0 .1 6- 1 .34Hz)治疗白鼠 ,在不同生物层次上 ,例如生物活体、器官、组织、细胞和大分子 ,能抑制鼠恶性肿瘤生长。结果 :上述磁场诱导癌细胞凋亡和阻塞供应肿瘤的新生血管。磁场对运动离子的洛仑兹力 ,使它们束缚在拉莫尔 (Larmor)半径以内 ,会影响正负带电离子对细胞膜和核膜的渗透能力 ,甚至在细胞膜和核膜上形成空洞。结论 :由于这一磁场抑制癌瘤生长 ,所以它能成为一种治疗癌瘤的新方法。     

脉冲电场和磁场对高血粘和高凝血影响的比较研究

比较研究脉冲电场和脉冲磁场对高血粘和高凝血的影响,探寻降低血液粘度,抑制凝血过快、过强的物理方法.每份血样等分9份,1份作对照,对另外8份分别作不同的脉冲电场或磁场处理.结果显示不同上升沿速率的脉冲电场和磁场对高血粘和高凝血的影响程度不同,上升沿速率为2.5 × 105T s-1的脉冲磁场使全血表观粘度η降低(P＜0.01)、复钙凝血时间tr变长(P＜0.01),血块的最大剪切应力τax变小(P＜0.01).脉冲磁场作用能改善高血粘和高凝血状况.     

超低频脉冲磁场抑制癌瘤和提高细胞免疫功能的实验研究

在报道用电子显微镜观测超低频脉冲磁场(峰值磁场0.6～2.0T,磁场梯度10～100T·m^-1,脉冲宽度20～200ms,重复频率0.16～1.34Hz)抑制鼠S-180肉瘤和加强免疫细胞溶癌作用以后,报道了用Faulgen染色法测定肉瘤细胞核的DNA倍性,和用电镜技术和细胞结构的体视学分析磁场对癌细胞形态的影响,观测到磁场影响癌细胞的代谢:磁场使癌细胞的恶性程度降低,抑制其高速和异形生长;磁场抑制癌细胞的分裂和DNA的复制;磁场提高细胞免疫功能,加强淋巴细胞、浆细胞反应.     

内植静磁柱联合脉冲电磁场对骨组织修复作用的Micro-CT研究

目的:以永磁体构建静磁柱体内植入物,应用Micro-CT技术,探索研究内植静磁柱联合脉冲电磁场对骨组织的修复作用。方法:选取新西兰兔24只建立右侧股骨髁骨缺损模型,并随机分为联合磁场组,脉冲电磁场组和对照组。联合磁场组自兔右侧股骨干远端向髓内植入静磁柱,并联合施加体外脉冲电磁场(1 h/d);脉冲电磁场组及对照组均将无磁性钛合金棒植入右侧股骨干髓腔,同时,脉冲电磁场组于体外加载脉冲电磁场(1 h/d)。术后5周处死取材,应用Micro-CT对股骨远端样本进行扫描检测,并对骨缺损区域显微结构进行三维重建分析。结果:与非磁场组相比,联合磁场组骨缺损区域骨小梁相对体积及数目明显增加(P均0.05),骨小梁分离度下降(P0.01)。与传统脉冲电磁场组相比,联合磁场组骨小梁数目增加(P0.05),骨小梁分离度下降(P0.01)。扫描及重建图像可见,联合磁场组骨缺损区域骨量增多,外侧皮质区愈合完整,骨小梁结构连续致密,具有更好的骨显微结构。结论:内植静磁柱与脉冲电磁场的联合磁场干预方式能够在早期获得更好的成骨修复能力,为磁场治疗相关骨病的临床及基础研究提供了新的方向。     

磁场处理山豆根药液对小白鼠肠推进运动的影响

用经0.1T和0.25T磁场处理山豆根药液灌小白鼠胃,分别测定它们对小白鼠肠推进运动的影响。实验结果显示:0.25T磁场处理山豆根药液对小白鼠肠推进活动有明显促进作用,而0.1T磁场处理山豆根药液对小白鼠肠推进活动不明显,实验表明达到一定强度磁场才影响山豆根药液的药效。     

海上风电磁场对12种海洋生物存活率与行为的影响

海上风电磁场主要由风电场运行中海底电缆产生,其对海洋生物产生的影响目前研究报道较少。为了掌握风电磁场是否对临近海域及养殖环境中的海洋生物产生影响,本研究以如东龙源风电示范区为例,选取江苏近海常见12种海洋生物,通过实验方法研究不同磁场强度(试验Ⅰ:1.00 m T;试验Ⅱ:0 m T、(0.045±0.01)m T、(0.20±0.01)m T、(0.90±0.01)m T、(4.05±0.01)m T、对照(自然地磁场))下,风电磁场对鱼、虾、蟹和贝类的存活、行为等方面的影响。结果表明:当磁场为1.00 m T时,黑鲷存活和行为在短期内(21 d)受磁场影响明显,试验组与对照组存活率差异显著(P0.05),磁场撤销后14 d内无显著性差异(P0.05);试验Ⅱ中,受试生物(黑鲷、半滑舌鳎、文蛤)的存活率仅在(4.05±0.01)m T磁场暴露下的试验组与对照组差异显著(P0.05);受试生物(纵肋织纹螺、半滑舌鳎、天津厚蟹)的行为在(4.05±0.01)m T磁场下试验组与对照组间均存在差异显著(P0.05)。由此可见:短期内(21 d),风电磁场对几种海洋生物的存活、行为有一定的影响,撤销磁场后影响消失。     

脉冲电磁场对C2C12 成肌细胞增殖影响的实验研究

目的:研究不同强度脉冲电磁场干预对成肌细胞增殖的影响。方法:10Hz脉冲低频电磁场刺激经复苏后培养贴壁良好的C2C12成肌细胞,根据不同磁场强度和作用时间将其分为A、B、C组,无磁场干预的为对照组。采用RT-q PCR检测不同磁场强度下成肌细胞标记基因Myf5、Myo D及Pax7的m RNA的表达。结果:经RT-q PCR检测三种基因的表达情况,Myf5 m RNA在1.5 m T磁场强度下照射第五天表达最高;0.5 m T磁场强度下Myf5 m RNA的表达与对照组相比无统计学意义(P>0.05);1.0 m T磁场强度下Myf5 m RNA表达与对照组比较差异具有统计学意义(P<0.05);1.5 m T磁场强度下Myf5 m RNA表达与对照组比较差异具有统计学意义(P<0.05)。对照组Myo D m RNA的表达要比磁场作用下表达要高。三个磁场强度下Myo D m RNA表达与对照组相比均无统计学意义(P>0.05)。0.5 m T、1.0 m T磁场强度下Pax7 m RNA的表达要比对照组要高,与对照组相比具有统计学意义(P<0.05);1.5 m T磁场强度下Pax7 m RNA表达与对照组相比无统计学意义(P>0.05)。结论 :1.5 m T脉冲电磁场强度下作用5天对体外培养的成肌细胞Myf5 m RNA标记基因增殖促进作用最强。     

磁场和磁场处理水对奥利亚罗非鱼(Tilapia Aurea’s)生长和耐寒力的影响

用磁场(0.07T)和磁场处理水(0.05T—0.7T)养殖奥利亚罗非鱼(Tilapia Aurea’s)观察其生长效应,并在人工缓慢降温、人工急剧降温和自然降温中观察对罗非鱼耐寒力的影响.实验表明,磁场和磁场处理水可促进罗非鱼生长,增强耐寒力,文中还分析了磁处理条件和机理问题.     

脉冲磁场对神经元动作电位发放的影响

磁场作用于生物体产生的生物效应被广泛研究。本文将脉冲磁场作用于神经元细胞,试图观察Na+通道的变化及其引起的动作电位的变化。选择频率15 Hz、强度1 mT的脉冲磁场刺激昆明小鼠大脑皮质神经元,随后进行全细胞膜片钳实验。结果显示,脉冲磁场延缓了Na+通道电流的激活,促进Na+通道电流的失活。基于经典的细胞三层介电模型,模拟了在脉冲磁场下细胞膜电位分布的极化图,结果显示诱发的膜电位大小与脉冲磁场的频率和强度有关。基于Hodgkin-Huxley(H-H)模型,仿真了脉冲磁场感应的电流作用于离子通道所产生的动作电位曲线,与不加刺激时候的曲线相比较,当外加电流在-1.32~0μA时,动作电位的产生频率减小,幅值降低;当外加电流大于0μA时,动作电位的产生频率增大,幅值变化不明显;当外加电流小于-1.32μA时,动作电位的上升时间快速变短,峰值剧烈降低,无法形成完整的动作电位,即无动作电位。以上结果提示,磁场刺激可通过调节Na+通道影响神经元动作电位的发放频率和幅值。     

Experimental studies on ultralow frequency pulsed gradient magnetic field inducing apoptosis of cancer cell and inhibiting growth of cancer cell

The morphology characteristics of cell apoptosis of the malignant tumour cells in magnetic field-treated mouse was observed for the first time. The apoptotic cancer cell contracted, became rounder and divorced from adjacent cells; the heterochromatin condensed and coagulated together along the inner side of the nuclear membrane; the endoplasmic reticulums(ER) expanded and fused with the cellular membrane; many apoptotic bodies which were packed by the cellular membrane appeared and were devoured by some lymphocytes and plasma. Apoptosis of cancer cells was detected by terminal deoxynucleotidyl transferase mediated in situ nick end labeling(TUNEL). It was found that the number of apoptosis cancer cells of the sample treated by the magnetic field is more than that of the control sample. The growth of malignant tumour in mice was inhibited and the ability of immune cell to dissolve cancer cells was improved by ultralow frequency(ULF) pulsed gradient magnetic field; the nuclei DNA contents decreased, indicating that magnetic field can block DNA replication and inhibit mitosis of cancer cells. It was suggested that magnetic field could inhibit the metabolism of cancer cell, lower its malignancy, and restrain its rapid and heteromorphic growth. Since ULF pulsed gradient magnetic field can induce apoptosis of cancer cells and inhibit the growth of malignant tumour, it could be used as a new method to treat cancer.     

Experimental studies on ultralow frequency pulsed gradient magnetic field inducing apoptosis of cancer cell and inhibiting growth of cancer cell

The morphology characteristics of cell apoptosis of the malignant tumour cells in magnetic field-treated mouse was observed for the first time. The apoptotic cancer cell contracted, became rounder and divorced from adjacent cells; the heterochromatin condensed and coagulated together along the inner side of the nuclear membrane; the endoplasmic reticulums (ER) expanded and fused with the cellular membrane; many apoptotic bodies which were packed by the cellular membrane appeared and were devoured by some lymphocytes and plasma. Apoptosis of cancer cells was detected by terminal deoxynucleotidyl transferase mediated in situ nick end labeling (TUNEL). It was found that the number of apoptosis cancer cells of the sample treated by the magnetic field is more than that of the control sample. The growth of malignant tumour in mice was inhibited and the ability of immune cell to dissolve cancer cells was improved by ultralow frequency (ULF) pulsed gradient magnetic field; the nuclei DNA contents decreased, indi     

Influence of a stationary magnetic field on water relations in lettuce seeds. Part I: theoretical considerations.

The theoretical calculation about the dependence of the ionic current density across the cellular membrane on the intensity of the magnetic field applied to cellular tissue is presented. This interaction induces changes in the magnitude of the ionic current density across the cellular membrane and in the ionic concentration, and it also causes alterations in the osmotic pressure and in the capacity of the cellular tissues to absorb water. The magnetic field dependence of the ionic current densities J(p) (B) (positive ions) and J(n) (B) (negative ions), the membrane conductivity sigma (B), the ionic concentration in both membrane sides c(B), the osmotic pressure pi (B), and the water uptake rate by seeds k(w) (B) are presented. The increase in water uptake rate due to the applied magnetic field may be the explanation of the recently reported increase in the germination speed of the seeds treated with stationary magnetic fields.     

Nanosecond electric pulses trigger actin responses in plant cells

We have analyzed the cellular effects of nanosecond pulsed electrical fields on plant cells using fluorescently tagged marker lines in the tobacco cell line BY-2 and confocal laser scanning microscopy. We observe a disintegration of the cytoskeleton in the cell cortex, followed by contraction of actin filaments towards the nucleus, and disintegration of the nuclear envelope. These responses are accompanied by irreversible permeabilization of the plasma membrane manifest as uptake of Trypan Blue. By pretreatment with the actin-stabilizing drug phalloidin, the detachment of transvacuolar actin from the cell periphery can be suppressed, and this treatment can also suppress the irreversible perforation of the plasma membrane. We discuss these findings in terms of a model, where nanosecond pulsed electric fields trigger actin responses that are key events in the plant-specific form of programmed cell death.     

Experimental studies on extremely low frequency pulsed magnetic field inhibiting sarcoma and enhancing cellular immune functions

The previous observation with an electron microscope showed that extremely low frequency (ELF) pulsed magnetic field (PMF) (with the maximum intensity of 0. 6-2. 0 T, gradient of 10-100 T. M-1, pulse width of 20-200 ms and frequency of 0. 16-1. 34 Hz) inhibited the growth of S-180 sarcoma in mice and enhanced the ability of immune cell's dissolving sarcoma cells. In this study, the DNA contents of nuclei were assayed by using Faulgen Staining method. With an electron microscope and cell stereoscopy technology it was observed that magnetic field affected the sarcoma cell's metabolism, lowered its malignancy, and restrained its rapid and heteromorphic growth. The magnetic field enhanced the cellular immune ability and the reaction of lymphocytes and plasma. Since ELF pulsed magnetic fields can inhibit the growth of sarcomas and enhance the cellular immune ability, it is possible to use it as a new method to treat cancer.     

DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic vesicles during programmed cell death

Death-associated protein kinase (DAPk) and DAPk-related protein kinase (DRP)-1 proteins are Ca+2/calmodulin-regulated Ser/Thr death kinases whose precise roles in programmed cell death are still mostly unknown. In this study, we dissected the subcellular events in which these kinases are involved during cell death. Expression of each of these DAPk subfamily members in their activated forms triggered two major cytoplasmic events: membrane blebbing, characteristic of several types of cell death, and extensive autophagy, which is typical of autophagic (type II) programmed cell death. These two different cellular outcomes were totally independent of caspase activity. It was also found that dominant negative mutants of DAPk or DRP-1 reduced membrane blebbing during the p55/tumor necrosis factor receptor 1-induced type I apoptosis but did not prevent nuclear fragmentation. In addition, expression of the dominant negative mutant of DRP-1 or of DAPk antisense mRNA reduced autophagy induced by antiestrogens, amino acid starvation, or administration of interferon-gamma. Thus, both endogenous DAPk and DRP-1 possess rate-limiting functions in these two distinct cytoplasmic events. Finally, immunogold staining showed that DRP-1 is localized inside the autophagic vesicles, suggesting a direct involvement of this kinase in the process of autophagy.     

The natural compound trans-chalcone induces programmed cell death in Arabidopsis thaliana roots

Chalcone (1,3-diphenyl-2-propen-1-one) is an aromatic ketone precursor of important molecules in plants such as flavonoids or anthocyanins. Its phytotoxicity has been demonstrated on different plant species, but to date little is known about the mechanisms of action of this secondary metabolite at plant cellular level. Detailed analysis by light and transmission electron microscopy (TEM) was conducted to examine the root meristems' ultrastructure of control and chalcone-treated Arabidopsis seedlings. Mitochondrial dysfunction was analysed by measuring mitochondrial membrane potential with JC-1 fluorochrome. Finally, acridine orange/ethidium bromide staining was used for the detection of programmed cell death. Microscopy revealed tissue alterations, inhibition of root hair formation and important changes after 7 and 14 d at the chalcone IC(50) value. Chalcone-treated cells showed signs of programmed cell death such as mitochondrial condensation, disruption of organelles and chromatin fragmentation. Acridine orange/ethidium bromide staining confirmed the programmed cell death, which could be induced by the reduction of mitochondrial transmembrane potential (ΔΨ(m)) that was detected after chalcone treatment. These results confirm the phytotoxic activity of chalcone on Arabidopsis seedlings, the alteration of mitochondrial membrane potential and the induction of programmed cell death.     

Macromitophagy,neutral lipids synthesis,and peroxisomal fatty acid oxidation protect yeast from “liponecrosis”, a previously unknown form of programmed cell death

We identified a form of cell death called “liponecrosis.” It can be elicited by an exposure of the yeast Saccharomyces cerevisiae to exogenous palmitoleic acid (POA). Our data imply that liponecrosis is: (1) a programmed, regulated form of cell death rather than an accidental, unregulated cellular process and (2) an age-related form of cell death. Cells committed to liponecrotic death: (1) do not exhibit features characteristic of apoptotic cell death; (2) do not display plasma membrane rupture, a hallmark of programmed necrotic cell death; (3) akin to cells committed to necrotic cell death, exhibit an increased permeability of the plasma membrane for propidium iodide; (4) do not display excessive cytoplasmic vacuolization, a hallmark of autophagic cell death; (5) akin to cells committed to autophagic death, exhibit a non-selective en masse degradation of cellular organelles and require the cytosolic serine/threonine protein kinase Atg1p for executing the death program; and (6) display a hallmark feature that has not been reported for any of the currently known cell death modalities—namely, an excessive accumulation of lipid droplets where non-esterified fatty acids (including POA) are deposited in the form of neutral lipids. We therefore concluded that liponecrotic cell death subroutine differs from the currently known subroutines of programmed cell death. Our data suggest a hypothesis that liponecrosis is a cell death module dynamically integrated into a so-called programmed cell death network, which also includes the apoptotic, necrotic, and autophagic modules of programmed cell death. Based on our findings, we propose a mechanism underlying liponecrosis.     

Histone H2AX: The missing link in AIF-mediated caspase-independent programmed necrosis

Caspase-independent programmed necrosis is a highly regulated cellular demise that displays morphological and biochemical necrotic hallmarks, such as an earlier permeability of the plasma membrane and lactate dehydrogenase (LDH) leakiness. This form of programmed cell death (PCD) is regulated by AIF, a FAD-dependent oxidoreductase, which is released from the mitochondria to the nucleus where it induces chromatin condensation and DNA fragmentation. Some years ago, it has been established that the sequential activation of poly(ADP-ribose) polymerase-1 (PARP-1), calpains, and Bax regulate the mitochondrial AIF release associated to programmed necrosis. But, what happens when AIF is in the nucleus? How does this protein induce chromatinolysis and programmed necrosis? Recently, we have unraveled some of the mechanisms underlying the nuclear action of AIF in this type of caspase-independent cell death. Indeed, AIF plays a key role in programmed necrosis by its ability to organize a DNA-degrading complex with H2AX and Cyclophiline A (CypA). The AIF/H2AX link is indeed a critical event and explains the nuclear AIF apoptogenic action. In the present article, we outline the current knowledge on cell death by programmed necrosis and discuss the relevance of the AIF/H2AX/CypA DNA-degrading complex in the regulation of this original form of cell death.     

Apoptosis-associated changes in the glycerophospholipid composition of hematopoietic progenitor cells monitored by 31P NMR spectroscopy and MALDI-TOF mass spectrometry

Apoptosis, or programmed cell death, plays an important role in development and in tissue homeostasis and is assumed to be accompanied by changes in the composition of cellular glycerophospholipids (GPL). We have applied a combination of ³¹P nuclear magnetic resonance spectroscopy and matrix-assisted laser desorption and ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to the analysis of organic extracts of hematopoietic progenitor cells undergoing the physiologically relevant process of apoptosis following growth factor withdrawal. The combined application of these methods enables the quantitative analysis of all glycerophospholipid classes and reveals changes in the acyl chain compositions from crude cell extracts. Using these techniques, an increase in the ratio of ether-linked glycerophospholipids to diacyl-glycerophospholipids during apoptosis was observed. The relative decrease in the membrane diacyl-phosphatidylcholine (PC) levels was found to correlate with increased concentrations of the corresponding lysophosphatidylcholine (LPC) present in the medium.