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Lung Ablation with Irreversible Electroporation Promotes Immune Cell Infiltration by Sparing Extracellular Matrix Proteins and Vasculature: Implications for Immunotherapy. 不可逆电穿孔肺消融通过保留细胞外基质蛋白和血管促进免疫细胞浸润:免疫治疗的意义。
IF 2.3 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-09-01 Epub Date: 2021-09-09 DOI: 10.1089/bioe.2021.0014
Masashi Fujimori, Yasushi Kimura, Eisuke Ueshima, Damian E Dupuy, Prasad S Adusumilli, Stephen B Solomon, Govindarajan Srimathveeravalli

Background: This study investigated the sparing of the extracellular matrix (ECM) and blood vessels at the site of lung irreversible electroporation (IRE), and its impact on postablation T cell and macrophage populations. Materials and Methods: Normal swine (n = 8) lung was treated with either IRE or microwave ablation (MWA), followed by sacrifice at 2 and 28 days (four animals/timepoint) after treatment. En bloc samples of ablated lung were stained for blood vessels (CD31), ECM proteins (Collagen, Heparan sulfate, and Decorin), T cells (CD3), and macrophages (Iba1). Stained slides were analyzed with an image processing software (ImageJ) to count the number of positive staining cells or the percentage area of tissue staining for ECM markers, and the statistical difference was evaluated with Student's t-test. Results: Approximately 50% of the blood vessels and collagen typically seen in healthy lung were evident in IRE treated samples at Day 2, with complete destruction within MWA treated lung. These levels increased threefold by Day 28, indicative of post-IRE tissue remodeling and regeneration. Decorin and Heparan sulfate levels were reduced, and it remained so through the duration of observation. Concurrently, numbers of CD3+ T cells and macrophages were not different from healthy lung at Day 2 after IRE, subsequently increasing by 2.5 and 1.5-fold by Day 28. Similar findings were restricted to the peripheral inflammatory rim of MWA samples, wherein the central necrotic regions remained acellular through Day 28. Conclusion: Acute preservation of blood vessels and major ECM components was observed in IRE treated lung at acute time points, and it was associated with the increased infiltration and presence of T cells and macrophages, features that were spatially restricted in MWA treated lung.

背景:本研究探讨肺不可逆电穿孔(IRE)部位的细胞外基质(ECM)和血管的保留及其对消融后T细胞和巨噬细胞群的影响。材料与方法:采用IRE或微波消融(MWA)治疗正常猪肺(n = 8),分别于治疗后2天和28天(4只动物/时间点)处死。整块肺切除标本进行血管(CD31)、ECM蛋白(胶原蛋白、硫酸肝素和Decorin)、T细胞(CD3)和巨噬细胞(Iba1)染色。用图像处理软件(ImageJ)对染色玻片进行分析,统计阳性染色细胞数或ECM标记物组织染色面积百分比,并采用Student’st检验评价统计学差异。结果:在第2天,IRE处理的样本中可以看到大约50%的正常肺中典型的血管和胶原蛋白,而在MWA处理的肺中完全破坏。这些水平在第28天增加了三倍,表明ire后的组织重塑和再生。Decorin和Heparan硫酸水平降低,并在观察期间保持不变。同时,在IRE后第2天,CD3+ T细胞和巨噬细胞的数量与健康肺没有差异,随后在第28天分别增加2.5倍和1.5倍。类似的发现仅限于MWA样本的外周炎症边缘,其中中央坏死区域在28天内保持无细胞性。结论:IRE治疗的肺在急性时间点可观察到血管和主要ECM成分的急性保存,并与T细胞和巨噬细胞的浸润和存在增加有关,这一特征在MWA治疗的肺中受到空间限制。
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引用次数: 8
Myocardial Edema Revisited in a New Paradigm of Cardiac Electrical Microcurrent Application in Heart Failure. 心肌水肿在心力衰竭心电微电流应用新范例中的重新审视
IF 2.3 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-09-01 Epub Date: 2021-09-09 DOI: 10.1089/bioe.2021.0021
Jesus Eduardo Rame, Johannes Müller

Undisturbed bioelectricity is a prerequisite for normal organ function. This is especially true for organs with high electrical activity such as the heart and the nervous system. Under clinical conditions, however, this can hardly be determined in patients with disturbed organ function and is therefore largely ignored. Here, based on clinical data, we will discuss whether the direct application of an external electric current (in the physiological μA range) together with an electrical field to hearts with impaired pump function can explain the functional improvement of the hearts by edema reduction triggered by electro-osmosis.

不受干扰的生物电是器官正常功能的先决条件。对于心脏和神经系统等电活动频繁的器官来说尤其如此。然而,在临床条件下,器官功能紊乱的患者很难确定这一点,因此在很大程度上被忽视了。在此,我们将以临床数据为基础,讨论对泵功能受损的心脏直接施加外部电流(在生理μA范围内)和电场是否可以解释电渗引发的水肿减轻对心脏功能改善的影响。
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引用次数: 0
Optical Estimation of Absolute Membrane Potential Using One- and Two-Photon Fluorescence Lifetime Imaging Microscopy. 利用单光子和双光子荧光寿命成像显微镜光学估计绝对膜电位。
IF 2.3 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-09-01 Epub Date: 2021-09-09 DOI: 10.1089/bioe.2021.0007
Julia R Lazzari-Dean, Evan W Miller

Background: Membrane potential (V mem) exerts physiological influence across a wide range of time and space scales. To study V mem in these diverse contexts, it is essential to accurately record absolute values of V mem, rather than solely relative measurements. Materials and Methods: We use fluorescence lifetime imaging of a small molecule voltage sensitive dye (VF2.1.Cl) to estimate mV values of absolute membrane potential. Results: We test the consistency of VF2.1.Cl lifetime measurements performed on different single-photon counting instruments and find that they are in striking agreement (differences of <0.5 ps/mV in the slope and <50 ps in the y-intercept). We also demonstrate that VF2.1.Cl lifetime reports absolute V mem under two-photon (2P) illumination with better than 20 mV of V mem resolution, a nearly 10-fold improvement over other lifetime-based methods. Conclusions: We demonstrate that VF-FLIM is a robust and portable metric for V mem across imaging platforms and under both one-photon and 2P illumination. This work is a critical foundation for application of VF-FLIM to record absolute membrane potential signals in thick tissue.

背景:膜电位(vmem)在广泛的时间和空间尺度上发挥生理影响。为了在这些不同的环境中研究V mem,必须准确记录V mem的绝对值,而不仅仅是相对测量值。材料和方法:利用小分子电压敏感染料(VF2.1.Cl)的荧光寿命成像来估计绝对膜电位的mV值。结果:检验了VF2.1的一致性。在不同的单光子计数仪器上进行了Cl寿命测量,发现它们具有惊人的一致性(y截距的差异)。我们还演示了VF2.1。Cl寿命报告了双光子(2P)照明下的绝对V mem分辨率优于20 mV,比其他基于寿命的方法提高了近10倍。结论:我们证明了VF-FLIM是跨成像平台、在单光子和2P照明下测量V - mem的稳健且便携的度量。该工作为应用VF-FLIM记录厚组织绝对膜电位信号奠定了重要基础。
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引用次数: 0
Effects of Pulsed Electromagnetic Field Intensity on Mesenchymal Stem Cells 脉冲电磁场强度对间充质干细胞的影响
IF 2.3 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-06-25 DOI: 10.1089/bioe.2021.0002
Luvita Suryani, Jyong Kiat Reuben Foo, A. Cardilla, Yibing Dong, P. Muthukumaran, A. Hassanbhai, F. Wen, D. Simon, D. Iandolo, N. Yu, K. Ng, S. Teoh
Introduction: Bone fractures remain a common injury. Nonunion fractures are often a serious complication where delays in tissue regeneration occur. The use of pulsed electromagnetic fields (PEMFs) ...
骨折仍然是一种常见的损伤。骨不连骨折通常是组织再生延迟的严重并发症。使用脉冲电磁场(pemf)…
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引用次数: 2
Nerve Impulses Have Three Interdependent Functions: Communication, Modulation, and Computation 神经冲动有三个相互依存的功能:沟通、调节和计算
IF 2.3 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-06-10 DOI: 10.1089/bioe.2021.0001
W. Winlow, A. S. Johnson
Comprehending the nature of action potentials is fundamental to our understanding of the functioning of nervous systems in general. Here we consider their evolution and describe their functions of communication, modulation and computation within nervous systems. The ionic mechanisms underlying action potentials in the squid giant axon were first described by Hodgkin and Huxley in 1952 and their findings have formed our orthodox view of how the physiological action potential functions. However, substantial evidence has now accumulated to show that the action potential is accompanied by a synchronized coupled soliton pressure pulse in the cell membrane, the action potential pulse (APPulse). Here we explore the interactions between the soliton and the ionic mechanisms known to be associated with the action potential. Computational models of the action potential usually describe it as a binary event, but we suggest that it is quantum ternary event known as the computational action potential (CAP), whose temporal fixed point is threshold, rather than the rather plastic action potential peak used in other models. The CAP accompanies the APPulse and the Physiological action potential. Therefore, we conclude that nerve impulses appear to be an ensemble of three inseparable, interdependent, concurrent states: the physiological action potential, the APPulse and the CAP.
理解动作电位的本质是我们理解神经系统功能的基础。在这里,我们考虑了它们的进化,并描述了它们在神经系统中的通信、调制和计算功能。1952年,霍奇金和赫胥利首次描述了鱿鱼巨轴突动作电位的离子机制,他们的发现形成了我们对生理动作电位如何起作用的正统观点。然而,目前已有大量证据表明,动作电位在细胞膜中伴随着一个同步耦合的孤子压力脉冲,即动作电位脉冲(APPulse)。在这里,我们探讨了已知与动作电位相关的孤子和离子机制之间的相互作用。动作电位的计算模型通常将其描述为二元事件,但我们认为它是量子三元事件,称为计算动作电位(CAP),其时间固定点为阈值,而不是其他模型中具有相当可塑性的动作电位峰值。CAP伴随着APPulse和生理动作电位。因此,我们得出结论,神经冲动似乎是三个不可分割,相互依存,并发状态的集合:生理动作电位,APPulse和CAP。
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引用次数: 3
Call for Special Issue Papers: The Bioelectricity of Connective Tissue Cells and their Environments: Deadline for Manuscript Submission: September 1, 2021. 特刊论文征集:结缔组织细胞及其环境的生物电:手稿提交截止日期:2021年9月1日。
IF 2.3 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-06-01 Epub Date: 2021-06-16 DOI: 10.1089/bioe.2020.29024.cfp1
Ali Mobasheri, Mary Maleckar
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引用次数: 0
Toward Bacterial Bioelectric Signal Transduction. 细菌生物电信号转导研究。
IF 2.3 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-06-01 Epub Date: 2021-06-16 DOI: 10.1089/bioe.2021.0013
Joshua M Jones, Joseph W Larkin

Bacteria are electrically powered organisms; cells maintain an electrical potential across their plasma membrane as a source of free energy to drive essential processes. In recent years, however, bacterial membrane potential has been increasingly recognized as dynamic. Those dynamics have been implicated in diverse physiological functions and behaviors, including cell division and cell-to-cell signaling. In eukaryotic cells, such dynamics play major roles in coupling bioelectrical stimuli to changes in internal cell states. Neuroscientists and physiologists have established detailed molecular pathways that transduce eukaryotic membrane potential dynamics to physiological and gene expression responses. We are only just beginning to explore these intracellular responses to bioelectrical activity in bacteria. In this review, we summarize progress in this area, including evidence of gene expression responses to stimuli from electrodes and mechanically induced membrane potential spikes. We argue that the combination of provocative results, missing molecular detail, and emerging tools makes the investigation of bioelectrically induced long-term intracellular responses an important and rewarding effort in the future of microbiology.

细菌是电力驱动的有机体;细胞在其质膜上保持一个电势,作为自由能的来源来驱动基本过程。然而,近年来,细菌膜电位越来越被认为是动态的。这些动力学涉及多种生理功能和行为,包括细胞分裂和细胞间信号传导。在真核细胞中,这种动力学在将生物电刺激耦合到细胞内部状态变化中起主要作用。神经科学家和生理学家已经建立了详细的分子途径,将真核生物膜电位动力学转化为生理和基因表达反应。我们才刚刚开始探索细菌对生物电活动的细胞内反应。在这篇综述中,我们总结了这一领域的进展,包括基因表达对电极刺激和机械诱导的膜电位峰值的反应的证据。我们认为,这些令人振奋的结果、缺失的分子细节和新兴工具的结合,使得对生物电诱导的长期细胞内反应的研究在未来的微生物学中是一项重要而有益的努力。
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引用次数: 3
Bringing Microbiology to Light: Toward All-Optical Electrophysiology in Bacteria. 揭示微生物学:细菌的全光电生理。
IF 2.3 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-06-01 Epub Date: 2021-06-16 DOI: 10.1089/bioe.2021.0008
Giuseppe Maria Paternò, Gaia Bondelli, Guglielmo Lanzani

The observation of neuron-like behavior in bacteria, such as the occurrence of electric spiking and extended bioelectric signaling, points to the role of membrane dynamics in prokaryotes. Electrophysiology of bacteria, however, has been overlooked for long time, due to the difficulties in monitoring bacterial bioelectric phenomena with those probing techniques that are commonly used for eukaryotes. Optical technologies can allow a paradigm shift in the field of electrophysiology of bacteria, as they would permit to elicit and monitor signaling rapidly, remotely, and with high spatiotemporal precision. In this perspective, we discuss about the potentiality of light interrogation methods in microbiology, encouraging the development of all-optical electrophysiology of bacteria.

对细菌中神经元样行为的观察,如电尖峰的发生和扩展的生物电信号传导,指出了膜动力学在原核生物中的作用。然而,细菌的电生理学长期以来一直被忽视,这是因为通常用于真核生物的探测技术难以监测细菌的生物电现象。光学技术可以使细菌电生理领域的范式转变,因为它们可以快速、远程和高时空精度地引发和监测信号。从这个角度出发,我们讨论了光询问方法在微生物学中的潜力,鼓励了细菌全光电生理的发展。
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引用次数: 6
Potential Roles for Gamma-Aminobutyric Acid Signaling in Bacterial Communities. γ -氨基丁酸信号在细菌群落中的潜在作用。
IF 2.3 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-06-01 Epub Date: 2021-06-16 DOI: 10.1089/bioe.2021.0012
Sarah J Quillin, Peter Tran, Arthur Prindle

It is now established that the gut microbiome influences human neurology and behavior, and vice versa. Distinct mechanisms underlying this bidirectional communication pathway, termed the gut-brain axis, are becoming increasingly uncovered. This review summarizes recent interkingdom signaling research focused on gamma-aminobutyric acid (GABA), a human neurotransmitter and ubiquitous signaling molecule found in bacteria, fungi, plants, invertebrates, and mammals. We detail how GABAergic signaling has been shown to be a crucial component of the gut-brain axis. We further describe how GABA is also being found to mediate interkingdom signaling between algae and invertebrates, plants and invertebrates, and plants and bacteria. Based on these emerging results, we argue that obtaining a complete understanding of GABA-mediated communication in the gut-brain axis will involve deciphering the role of GABA signaling and metabolism within bacterial communities themselves.

现在已经确定,肠道微生物组影响人类神经学和行为,反之亦然。这种被称为肠-脑轴的双向通讯通路的独特机制正逐渐被发现。伽马氨基丁酸(GABA)是一种人类神经递质,是细菌、真菌、植物、无脊椎动物和哺乳动物中普遍存在的信号分子。我们详细说明了gaba能信号如何被证明是肠-脑轴的关键组成部分。我们进一步描述了GABA是如何被发现介导藻类和无脊椎动物、植物和无脊椎动物以及植物和细菌之间的界间信号传导的。基于这些新出现的结果,我们认为要全面了解GABA介导的肠-脑轴通信将涉及破译GABA信号和细菌群落本身代谢的作用。
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引用次数: 12
Finding the Spark. 找到火花。
IF 2.3 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2021-06-01 Epub Date: 2021-06-16 DOI: 10.1089/bioe.2021.0017
Joel M Kralj

It began, as with many good things, at a happy hour. Adam Cohen, a young assistant professor asked whether rhodopsins could be used to optically sense voltage. In the heady days of 2009, channel rhodopsin had just been unveiled as a voltage actuator in neurons. Adam had the insight to question whether rhodopsins could be run in reverse; could optical changes in a protein relay the cellular voltage state using light? This was one of the earliest lessons I learned under his mentorship, and the first piece of advice in this retrospective-turning a scientific question or statement on its head can be the basis for many fantastic research projects.

像许多美好的事情一样,它开始于一个愉快的时刻。年轻的助理教授亚当·科恩(Adam Cohen)问道,视紫红质是否可以用于光学感应电压。在2009年令人兴奋的日子里,通道视紫红质刚刚被发现是神经元中的电压致动器。亚当对视紫红质是否可以反向运行提出了质疑;蛋白质的光学变化可以利用光来传递细胞电压状态吗?这是我在他的指导下学到的最早的一课,也是我在回顾过程中得到的第一个建议——将一个科学问题或陈述颠倒过来,可以成为许多了不起的研究项目的基础。
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引用次数: 0
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Bioelectricity
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