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The Immunogenic Connection of Thermal and Nonthermal Molecular Effects in Modulated Electro-Hyperthermia 调制电热疗法中热和非热分子效应的免疫原性联系

Open Journal of Biophysics

Pub Date : 2023-01-01 DOI: 10.4236/ojbiphy.2023.134007

Attila Marcell Szász, Gergö Lóránt, András Szász, Gyula Szigeti

Hyperthermia in oncology is an emerging complementary therapy. The clinical results depend on multiple conditional factors, like the type of cancer, the stage, the applied treatment device, and the complementary conventional therapy. The molecular effect could also be different depending on the temperature, heating dose, kind of energy transfer, and timing sequences compared to the concomitant treatment. This article examines the molecular impacts of a specific technique used in oncological hyperthermia called modulated electro-hyperthermia (mEHT). What sets mEHT apart is its emphasis on harnessing the combined effects of thermal and nonthermal factors. Nonthermal energy absorption occurs through the excitation of molecules, while the thermal component ensures the ideal conditions for this process. The applied radiofrequency current selects the malignant cells, and the modulation drives the nonthermal effects to immunogenic cell death, helping to develop tumor-specific antitumoral immune reactions. The synergy of the thermal and nonthermal components excites the lipid-assembled clusters of transmembrane proteins (membrane rafts) as the channels of transient receptor potentials (TRPs), the heat-shock proteins (HSPs), the voltage-gated channels, and the voltage-sensitive phosphatases (VSPs). All these transmembrane compartments channeling various ionic species (like calcium and proton) interact with the cytoskeleton and are involved in the apoptotic signal pathways.

肿瘤热疗是一种新兴的辅助疗法。临床结果取决于多种条件因素，如癌症的类型、分期、应用的治疗设备和补充的常规疗法。与伴随治疗相比，分子效应也可能因温度、加热剂量、能量转移种类和时间顺序而有所不同。本文探讨了一种用于肿瘤热疗的特定技术的分子影响，称为调制电热疗(mEHT)。mEHT的与众不同之处在于它强调利用热和非热因素的综合影响。非热能吸收是通过分子的激发发生的，而热组分保证了这一过程的理想条件。应用射频电流选择恶性细胞，调制驱动非热效应导致免疫原性细胞死亡，有助于产生肿瘤特异性抗肿瘤免疫反应。热和非热组分的协同作用激发了脂质组装的跨膜蛋白簇(膜筏)，作为瞬时受体电位(TRPs)、热休克蛋白(HSPs)、电压门控通道和电压敏感磷酸酶(VSPs)的通道。所有这些跨膜腔室引导各种离子(如钙和质子)与细胞骨架相互作用，并参与凋亡信号通路。

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引用次数: 0

Impact of Novel Pulsed Electromagnetic Field Device on Competitive Athlete Performance 新型脉冲电磁场装置对竞技运动员成绩的影响

Open Journal of Biophysics

Pub Date : 2023-01-01 DOI: 10.4236/ojbiphy.2023.134006

Dale C. Gledhill, Kade Huntsman, Gregory S. Anderson

The interaction of pulsed electromagnetic fields (PEMF) with the human body may result in a variety of positive outcomes including analgesia, enhanced healing, chondroprotection, cognitive improvement and better quality of life. Previous human studies have also revealed the potential of PEMF to enhance muscle function and athletic performance. To further evaluate this potential, an open label pilot study was conducted with 19 competitive cyclists who repeatedly participated in 63 training routes. Cyclist performance was tracked before and during use of a novel and portable PEMF device that is worn as a wristband. Comparison of performance before and during use of the wristband revealed a significant association with improved muscle power. The odds ratio was 3.02 (P < 0.01) for experiencing increased muscle power while wearing the PEMF device. Among the cycling routes in which an increase was observed, the average increase in power was about 9.8%. The data suggests the novel PEMF technology may be a safe and effective therapeutic approach for improved physical performance and likely involves improved oxygen delivery due to reduced rouleaux (erythrocyte aggregation). These results warrant further investigation comprising larger studies and additional outcomes.

脉冲电磁场(PEMF)与人体的相互作用可能导致各种积极的结果，包括镇痛、增强愈合、软骨保护、认知改善和更好的生活质量。先前的人体研究也揭示了PEMF在增强肌肉功能和运动表现方面的潜力。为了进一步评估这种潜力，对19名竞技自行车运动员进行了一项开放标签的试点研究，他们反复参加了63条训练路线。骑车者在使用一种新型便携式PEMF装置之前和期间的表现被跟踪，该装置作为腕带佩戴。在使用腕带之前和期间的性能比较揭示了与改善肌肉力量的显着关联。佩戴PEMF装置时肌肉力量增加的优势比为3.02 (P < 0.01)。在观察到功率增加的骑行路线中，平均功率增加约为9.8%。数据表明，新型PEMF技术可能是一种安全有效的治疗方法，可以改善身体机能，并可能通过减少rouleaux(红细胞聚集)来改善氧气输送。这些结果值得进一步的调查，包括更大的研究和其他结果。

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引用次数: 0

Memristor Hypothesis in Malignant Charge Distribution 恶性电荷分布中的忆阻假说

Open Journal of Biophysics

Pub Date : 2023-01-01 DOI: 10.4236/ojbiphy.2023.134005

Andras Szasz

Tissues in biological objects from the point of view of electromagnetic effects must be modeled not only for their conductivity. The ionic double layer induced by the electric field, built by electrolytic diffusion, must be counted. The micro (frequency dispersion phenomena) and macro (interfacial polarization), as well as more generalized by Nernst-Planck cells describe the biophysical aspects of this phenomena. The charge distribution depends on the processes and produces charge gradients in space. The dynamic feasibility of the-charge transition layer has memory and adaptability, working like a memristor in cancerous development. The memristor processes may complete the adaptation mechanisms of cancer cells to extremely stressful conditions. Our objective is to show the distribution and redistribution of space charges that generate memristors and internal currents like injury current (IC) in the development of cancer. We show some connected aspects of the modulated electrohyperthermia (mEHT) limiting the proliferation process in the micro-range like the macro-range electrochemotherapy (ECT) processes do. The internal polarization effects form space-charge, which characteristically differ in malignant and healthy environments. The electrical resistivity of the electrolytes depends on the distribution of the charges and concentrations of ions in the electrolytes, consequently the space-charge differences appear in the conductivity parameters too. The polarization heterogeneities caused by the irregularities of the healthy tissue induce a current (called injury current), which appears in the cancerous tumor as well. Due to the nonlinearity of the space-charge production and the differences of the relaxation time of the processes in various subunits. The tumor develops the space-charge which appears as an inductive component in the otherwise capacitive setting and forms a memristive behavior of the tumorous tissue. This continuously developing space-charge accommodates the tumor to the permanently changing conditions and helps the adopting the malignant cells in the new environment. Applying external radiofrequency electric field, the disturbance of the space-charge may change the conditions, and seek to reestablish the healthy homeostatic equilibrium, blocking the pathologic injury current components. The hypothetical memristive behavior of the tumor microenvironment and the tumor mass may be a biophysical addition to the adaption mechanisms of tumor cell and could provide a way to block the pathogen biophysical processes. An electric field in the direction of the place of disturbance from the healthy neighborhood appears, starting a current, which promotes cell migrations and wound healing, re-establishing homeostatic equilibrium. In pathological disturbance, the same process starts, which supports further proliferation, so its blocking is desired.

从电磁效应的角度来看，生物物体中的组织不仅要对其导电性进行建模。电解扩散形成的由电场诱导的离子双层必须计算在内。微观(频散现象)和宏观(界面极化)，以及更广义的能思-普朗克细胞描述了这种现象的生物物理方面。电荷分布取决于过程，并在空间上产生电荷梯度。电荷过渡层的动态可行性具有记忆性和适应性，在癌变过程中起着忆阻器的作用。忆阻过程可能完成癌细胞对极端应激条件的适应机制。我们的目标是展示在癌症发展过程中产生记忆电阻和内部电流(如损伤电流(IC))的空间电荷的分布和再分布。我们展示了调制电热(mEHT)在微观范围内限制增殖过程的一些相关方面，就像宏观范围的电疗(ECT)过程一样。内部极化效应形成空间电荷，在恶性环境和健康环境中具有不同的特征。电解质的电阻率取决于电解质中电荷的分布和离子的浓度，因此电导率参数也出现空间电荷差异。由健康组织的不规则性引起的极化不均匀性引起电流(称为损伤电流)，这种电流也出现在癌性肿瘤中。由于空间电荷产生的非线性和各子单元过程弛豫时间的差异。肿瘤产生空间电荷，在其他电容设置中表现为电感成分，并形成肿瘤组织的记忆行为。这种不断发展的空间电荷使肿瘤适应不断变化的环境，有助于恶性细胞在新的环境中适应。施加外部射频电场，空间电荷的扰动可以改变条件，寻求重建健康的稳态平衡，阻断病理性损伤电流组分。假设肿瘤微环境和肿瘤块的记忆行为可能是肿瘤细胞适应机制的生物物理补充，并可能提供阻断病原体生物物理过程的方法。来自健康邻居的干扰方向的电场出现，启动电流，促进细胞迁移和伤口愈合，重新建立稳态平衡。在病理紊乱中，同样的过程开始，这支持进一步的增殖，所以它的阻断是可取的。

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引用次数: 0

Free Volume in Membranes: Viscosity or Tension? 膜中的自由体积:粘度还是张力?

Open Journal of Biophysics

Pub Date : 2015-07-01 Epub Date: 2015-07-22 DOI: 10.4236/ojbiphy.2015.53007

V S Markin, F Sachs

Many papers have used fluorescent probe diffusion to infer membrane viscosity but the measurement is actually an assay of the free volume of the membrane. The free volume is also related to the membrane tension. Thus, changes in probe mobility refer equally well to changes in membrane tension. In complicated structures like cell membranes, it appears more intuitive to consider variations in free volume as referring to the effect of domains structures and interactions with the cytoskeleton than changes in viscosity since tension is a state variable and viscosity is not.

许多论文使用荧光探针扩散来推断膜粘度，但测量实际上是对膜自由体积的测定。自由体积也与膜张力有关。因此，探针迁移率的变化同样适用于膜张力的变化。在像细胞膜这样的复杂结构中，考虑自由体积的变化是指结构域的影响和与细胞骨架的相互作用，而不是粘度的变化，因为张力是一个状态变量，而粘度不是。

引用次数: 13

Prospective Development of Small Molecule Targets to Oncogenic Ras Proteins. 致癌Ras蛋白小分子靶点的前景研究。

Open Journal of Biophysics

Pub Date : 2013-10-01 DOI: 10.4236/ojbiphy.2013.34025

Reena Chandrashekar, Paul D Adams

Abnormal expression or mutations in Ras proteins has been found in up to 30% of cancer cell types, making them excellent protein models to probe structure-function relationships of cell-signaling processes that mediate cell transformtion. Yet, there has been very little development of therapies to help tackle Ras-related diseased states. The development of small molecules to target Ras proteins to potentially inhibit abnormal Ras-stimulated cell signaling has been conceptualized and some progress has been made over the last 16 or so years. Here, we briefly review studies characterizing Ras protein-small molecule interactions to show the importance and potential that these small molecules may have for Ras-related drug discovery. We summarize recent results, highlighting small molecules that can be directly targeted to Ras using Structure-Based Drug Design (SBDD) and Fragment-Based Lead Discovery (FBLD) methods. The inactivation of Ras oncogenic signaling in vitro by small molecules is currently an attractive hurdle to try to and leap over in order to attack the oncogenic state. In this regard, important features of previously characterized properties of small molecule Ras targets, as well as a current understanding of conformational and dynamics changes seen for Ras-related mutants, relative to wild type, must be taken into account as newer small molecule design strategies towards Ras are developed.

在多达30%的癌细胞类型中发现了Ras蛋白的异常表达或突变，使其成为探索介导细胞转化的细胞信号过程结构-功能关系的优秀蛋白质模型。然而，帮助治疗ras相关疾病的治疗方法却很少。开发靶向Ras蛋白的小分子来潜在地抑制Ras刺激的异常细胞信号传导已经概念化，并且在过去16年左右的时间里取得了一些进展。在这里，我们简要回顾了Ras蛋白与小分子相互作用的研究，以表明这些小分子对Ras相关药物发现的重要性和潜力。我们总结了最近的研究结果，重点介绍了使用基于结构的药物设计(SBDD)和基于片段的先导物发现(FBLD)方法可以直接靶向Ras的小分子。体外小分子对Ras致癌信号的失活目前是一个有吸引力的障碍，试图跨越以攻击致癌状态。在这方面，随着新的Ras小分子设计策略的发展，必须考虑到先前表征的小分子Ras靶点特性的重要特征，以及目前对Ras相关突变体相对于野生型的构象和动力学变化的理解。

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引用次数: 6

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