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Assessing the Impact of Agents with Antiviral Activities on Transmembrane Ionic Currents: Exploring Possible Unintended Actions 评估具有抗病毒活性的制剂对跨膜离子电流的影响:探索可能的意外作用
Pub Date : 2024-03-27 DOI: 10.3390/biophysica4020009
Geng-Bai Lin, Chia-Lung Shih, R. Liutkeviciene, V. Rovite, E. So, Chaochao Wu, Sheng Nan Wu
As the need for effective antiviral treatment intensifies, such as with the coronavirus disease 19 (COVID-19) infection, it is crucial to understand that while the mechanisms of action of these drugs or compounds seem apparent, they might also interact with unexplored targets, such as cell membrane ion channels in diverse cell types. In this review paper, we demonstrate that many different drugs or compounds, in addition to their known interference with viral infections, may also directly influence various types of ionic currents on the surface membrane of the host cell. These agents include artemisinin, cannabidiol, memantine, mitoxantrone, molnupiravir, remdesivir, SM-102, and sorafenib. If achievable at low concentrations, these regulatory effects on ion channels are highly likely to synergize with the identified initial mechanisms of viral replication interference. Additionally, the immediate regulatory impact of these agents on the ion-channel function may potentially result in unintended adverse effects, including changes in cardiac electrical activity and the prolongation of the QTc interval. Therefore, it is essential for patients receiving these related agents to exercise additional caution to prevent unnecessary complications.
随着有效抗病毒治疗需求的增加,如冠状病毒疾病 19(COVID-19)感染,了解这些药物或化合物的作用机制似乎显而易见,但它们也可能与未探索的靶点(如不同类型细胞中的细胞膜离子通道)发生相互作用,这一点至关重要。在这篇综述论文中,我们证明了许多不同的药物或化合物除了已知的干扰病毒感染外,还可能直接影响宿主细胞表面膜上的各种离子电流。这些药物包括青蒿素、大麻二酚、美金刚、米托蒽醌、莫诺吡拉韦、雷米替韦、SM-102 和索拉非尼。如果可以在低浓度下实现,这些对离子通道的调节作用极有可能与已确定的病毒复制干扰初始机制产生协同效应。此外,这些药物对离子通道功能的直接调节作用可能会导致意想不到的不良反应,包括心电活动改变和 QTc 间期延长。因此,接受这些相关药物治疗的患者必须格外谨慎,以防止出现不必要的并发症。
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引用次数: 0
Constant-pH Simulations of a Coarse-Grained Model of Polyfunctional Weak Charged Biopolymers 多官能团弱电荷生物聚合物粗粒模型的恒pH模拟
Pub Date : 2024-02-28 DOI: 10.3390/biophysica4010008
David Naranjo, Pablo M. Blanco, J. Garcés, S. Madurga, Francesc Mas
A coarse-grained model of linear polyfunctional weak charged biopolymers was implemented, formed of different proportions of acid-base groups resembling the composition of humic substances. These substances are mainly present in dissolved organic matter in natural water. The influence of electrostatic interactions computing methods, factors concerning the structure of the chain, different functional groups, and the ionic strength on polyelectrolytes were studied. Langevin dynamics with constant pH simulations were performed using the ESPResSO package and the Python-based Molecule Builder for ESPResSo (pyMBE) library. The coverage was fitted to a polyfunctional Frumkin isotherm, with a mean-field interaction between charged beads. The composition of the chain affects the charge while ionic strength affects both the charge and the radius of gyration. Additionally, the parameters intrinsic to the polyelectrolyte model were well reproduced by fitting the polyfunctional Frumkin isotherm. In contrast, the non-intrinsic parameters depended on the ionic strength. The method developed and applied to a polyfunctional polypeptide model, that resembles a humic acid, will be very useful for characterizing biopolymers with several acid-base functional groups, where their structure, the composition of the different functional groups, and the determination of the main intrinsic proton binding constants and their proportion are not exactly known.
该模型由不同比例的酸碱基团组成,与腐殖质的组成相似。这些物质主要存在于天然水中的溶解有机物中。研究了静电相互作用计算方法、链结构相关因素、不同功能基团以及离子强度对聚电解质的影响。使用 ESPResSO 软件包和基于 Python 的 ESPResSO 分子生成器(pyMBE)库进行了恒定 pH 值的朗格文动力学模拟。覆盖范围被拟合为多官能弗鲁姆金等温线,带电珠之间存在均场相互作用。链的组成会影响电荷,而离子强度会影响电荷和回转半径。此外,通过拟合多官能弗鲁姆金等温线,很好地再现了聚电解质模型的固有参数。相反,非固有参数取决于离子强度。所开发并应用于类似腐植酸的多官能团多肽模型的方法,对于表征具有多个酸碱官能团的生物聚合物非常有用,因为这些生物聚合物的结构、不同官能团的组成、主要内在质子结合常数及其比例的确定都不完全清楚。
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引用次数: 0
The Signature of Fluctuations of the Hydrogen Bond Network Formed by Water Molecules in the Interfacial Layer of Anionic Lipids 阴离子脂质界面层中水分子形成的氢键网络的波动特征
Pub Date : 2024-02-21 DOI: 10.3390/biophysica4010007
Ana-Marija Pavlek, Barbara Pem, Danijela Bakarić
As the water molecules found at the interface of lipid bilayers exhibit distinct structural and reorientation dynamics compared to water molecules found in bulk, the fluctuations in their hydrogen bond (HB) network are expected to be different from those generated by the bulk water molecules. The research presented here aims to gain an insight into temperature-dependent fluctuations of a HB network of water molecules found in an interfacial layer of multilamellar liposomes (MLVs) composed of anionic 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine (DMPS) lipids. Besides suspending DMPS lipids in phosphate buffer saline (PBS) of different pH values (6.0, 7.4, and 8.0), the changes in HB network fluctuations were altered by the incorporation of a non-polar flavonoid molecule myricetin (MCE) within the hydrocarbon chain region. By performing a multivariate analysis on the water combination band observed in temperature-dependent FTIR spectra, the results of which were further mathematically analyzed, the temperature-dependent fluctuations of interfacial water molecules were captured; the latter were the greatest for DMPS in PBS with a pH value of 7.4 and in general were greater for DMPS multibilayers in the absence of MCE. The presence of MCE made DMPS lipids more separated, allowing deeper penetration of water molecules towards the non-polar region and their restricted motion that resulted in decreased fluctuations. The experimentally observed results were supported by MD simulations of DMPS (+MCE) lipid bilayers.
由于脂质双分子层界面上的水分子与大分子中的水分子相比具有不同的结构和重新定向动力学,因此其氢键(HB)网络的波动预计与大分子水分子产生的波动不同。本文的研究旨在深入了解由阴离子 1,2-二肉豆蔻酰-sn-甘油-3-磷酸-L-丝氨酸(DMPS)脂质组成的多胶束脂质体(MLVs)界面层中水分子氢键网络随温度变化的波动情况。除了将DMPS脂质悬浮在不同pH值(6.0、7.4和8.0)的磷酸盐缓冲盐水(PBS)中外,在碳氢链区域加入非极性黄酮类分子杨梅素(MCE)也会改变HB网络波动的变化。通过对随温度变化的傅立叶变换红外光谱中观察到的水结合带进行多元分析,并进一步对分析结果进行数学分析,可以捕捉到界面水分子随温度变化的波动;在 pH 值为 7.4 的 PBS 中,DMPS 的界面水分子波动最大,而在没有 MCE 的情况下,DMPS 多层膜的界面水分子波动一般更大。MCE 的存在使 DMPS 脂质更加分离,使水分子更深地渗透到非极性区域,并限制了水分子的运动,从而导致波动减小。DMPS(+MCE)脂质双层膜的 MD 模拟证实了实验观察到的结果。
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引用次数: 0
Direct Interaction of Zirconia Nanoparticles with Human Immune Cells 氧化锆纳米颗粒与人类免疫细胞的直接相互作用
Pub Date : 2024-02-14 DOI: 10.3390/biophysica4010006
A. Barbasz, Barbara Dyba
Nanomaterials play a crucial role in various aspects of modern life. Zirconia nanoparticles, extensively employed in medicine for fortifying and stabilizing implants in reconstructive medicine, exhibit unique electrical, thermal, catalytic, sensory, optical, and mechanical properties. While these nanoparticles have shown antibacterial activity, they also exhibit cytotoxic effects on human cells. Our research focuses on understanding how the cells of the human immune system (both the innate response, namely HL-60 and U-937, and the acquired response, namely HUT-78 and COLO-720L) respond to the presence of zirconium (IV) oxide nanoparticles (ZrO2-NPs). Viability tests indicate that ZrO2-NPs exert the highest cytotoxicity on HL-60 > U-937 > HUT-78 > COLO 720L cell lines. Notably, concentrations exceeding 100 μg mL−1 of ZrO2-NPs result in significant cytotoxicity. These nanoparticles readily penetrate the cell membrane, causing mitochondrial damage, and their cytotoxicity is associated with heightened oxidative stress in cells. The use of ZrO2-NP-based materials may pose a risk to immune system cells, the first responders to foreign entities in the body. Biofunctionalizing the surface of ZrO2-NPs could serve as an effective strategy to mitigate cytotoxicity and introduce new properties for biomedical applications.
纳米材料在现代生活的各个方面都发挥着至关重要的作用。氧化锆纳米粒子被广泛应用于医学领域,用于加固和稳定重建医学中的植入物,具有独特的电、热、催化、感官、光学和机械特性。虽然这些纳米粒子具有抗菌活性,但它们对人体细胞也有细胞毒性作用。我们的研究重点是了解人体免疫系统细胞(先天性反应,即 HL-60 和 U-937,以及后天性反应,即 HUT-78 和 COLO-720L)如何对氧化锆 (IV) 纳米粒子(ZrO2-NPs)的存在做出反应。活力测试表明,ZrO2-NPs 对 HL-60 > U-937 > HUT-78 > COLO 720L 细胞系的细胞毒性最高。值得注意的是,浓度超过 100 μg mL-1 的 ZrO2-NPs 会产生显著的细胞毒性。这些纳米粒子很容易穿透细胞膜,造成线粒体损伤,其细胞毒性与细胞氧化应激加剧有关。使用基于 ZrO2-NP 的材料可能会给免疫系统细胞带来风险,而免疫系统细胞是体内外来物质的第一反应者。对 ZrO2-NPs 表面进行生物功能化处理可作为一种有效的策略来减轻细胞毒性,并为生物医学应用引入新的特性。
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引用次数: 0
Direct Interaction of Zirconia Nanoparticles with Human Immune Cells 氧化锆纳米颗粒与人类免疫细胞的直接相互作用
Pub Date : 2024-02-14 DOI: 10.3390/biophysica4010006
A. Barbasz, Barbara Dyba
Nanomaterials play a crucial role in various aspects of modern life. Zirconia nanoparticles, extensively employed in medicine for fortifying and stabilizing implants in reconstructive medicine, exhibit unique electrical, thermal, catalytic, sensory, optical, and mechanical properties. While these nanoparticles have shown antibacterial activity, they also exhibit cytotoxic effects on human cells. Our research focuses on understanding how the cells of the human immune system (both the innate response, namely HL-60 and U-937, and the acquired response, namely HUT-78 and COLO-720L) respond to the presence of zirconium (IV) oxide nanoparticles (ZrO2-NPs). Viability tests indicate that ZrO2-NPs exert the highest cytotoxicity on HL-60 > U-937 > HUT-78 > COLO 720L cell lines. Notably, concentrations exceeding 100 μg mL−1 of ZrO2-NPs result in significant cytotoxicity. These nanoparticles readily penetrate the cell membrane, causing mitochondrial damage, and their cytotoxicity is associated with heightened oxidative stress in cells. The use of ZrO2-NP-based materials may pose a risk to immune system cells, the first responders to foreign entities in the body. Biofunctionalizing the surface of ZrO2-NPs could serve as an effective strategy to mitigate cytotoxicity and introduce new properties for biomedical applications.
纳米材料在现代生活的各个方面都发挥着至关重要的作用。氧化锆纳米粒子被广泛应用于医学领域,用于加固和稳定重建医学中的植入物,具有独特的电、热、催化、感官、光学和机械特性。虽然这些纳米粒子具有抗菌活性,但它们对人体细胞也有细胞毒性作用。我们的研究重点是了解人体免疫系统细胞(先天性反应,即 HL-60 和 U-937,以及后天性反应,即 HUT-78 和 COLO-720L)如何对氧化锆 (IV) 纳米粒子(ZrO2-NPs)的存在做出反应。活力测试表明,ZrO2-NPs 对 HL-60 > U-937 > HUT-78 > COLO 720L 细胞系的细胞毒性最高。值得注意的是,浓度超过 100 μg mL-1 的 ZrO2-NPs 会产生显著的细胞毒性。这些纳米粒子很容易穿透细胞膜,造成线粒体损伤,其细胞毒性与细胞氧化应激加剧有关。使用基于 ZrO2-NP 的材料可能会给免疫系统细胞带来风险,而免疫系统细胞是体内外来物质的第一反应者。对 ZrO2-NPs 表面进行生物功能化处理可作为一种有效的策略来减轻细胞毒性,并为生物医学应用引入新的特性。
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引用次数: 0
Neurite Growth and Electrical Activity in PC-12 Cells: Effects of H3 Receptor-Inspired Electromagnetic Fields and Inherent Schumann Frequencies PC-12 细胞的神经元生长和电活动:H3 受体激发的电磁场和固有舒曼频率的影响
Pub Date : 2024-02-07 DOI: 10.3390/biophysica4010005
Landon M. Lefebvre, Adam D. Plourde-Kelly, K. Saroka, B. Dotta
Cells are continually exposed to a range of electromagnetic fields (EMFs), including those from the Schumann resonance to radio waves. The effects of EMFs on cells are diverse and vary based on the specific EMF type. Recent research suggests potential therapeutic applications of EMFs for various diseases. In this study, we explored the impact of a physiologically patterned EMF, inspired by the H3 receptor associated with wakefulness, on PC-12 cells in vitro. Our hypothesis posited that the application of this EMF to differentiated PC-12 cells could enhance firing patterns at specific frequencies. Cell electrophysiology was assessed using a novel device, allowing the computation of spectral power density (SPD) scores for frequencies between 1 Hz and 128 Hz. T-tests comparing SPD at certain frequencies (e.g., 29 Hz, 30 Hz, and 79 Hz) between the H3-EMF and control groups showed a significantly higher SPD in the H3 group (p < 0.050). Moreover, at 7.8 Hz and 71 Hz, a significant correlation was observed between predicted and percentages of cells with neurites (R = 0.542). Key findings indicate the efficacy of the new electrophysiology measure for assessing PC-12 cell activity, a significant increase in cellular activity with the H3-receptor-inspired EMF at specific frequencies, and the influence of 7.8 Hz and 71 Hz frequencies on neurite growth. The overall findings support the idea that the electrical frequency profiles of developing cell systems can serve as an indicator of their progression and eventual cellular outcomes.
细胞持续暴露于各种电磁场(EMF),包括从舒曼共振到无线电波的电磁场。电磁场对细胞的影响多种多样,并根据具体的电磁场类型而有所不同。最近的研究表明,电磁场具有治疗各种疾病的潜力。在本研究中,我们探讨了生理模式电磁场对体外 PC-12 细胞的影响,这种电磁场受与觉醒相关的 H3 受体的启发。我们的假设是,将这种电磁场应用于分化的 PC-12 细胞可增强特定频率的发射模式。细胞电生理学评估采用了一种新型设备,可计算出 1 赫兹到 128 赫兹频率的频谱功率密度 (SPD) 分数。对 H3-EMF 组和对照组在某些频率(如 29 Hz、30 Hz 和 79 Hz)的 SPD 进行 T 检验,结果显示 H3 组的 SPD 明显更高(p < 0.050)。此外,在 7.8 Hz 和 71 Hz 时,预测值与神经元细胞百分比之间存在显著相关性(R = 0.542)。主要研究结果表明,新的电生理学测量方法可有效评估 PC-12 细胞的活性,在特定频率下,受 H3 受体启发的电磁场可显著提高细胞活性,而且 7.8 赫兹和 71 赫兹的频率对神经元生长有影响。总体研究结果支持这样一种观点,即发育中细胞系统的电频率曲线可作为其进展和最终细胞结果的指标。
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引用次数: 0
Neurite Growth and Electrical Activity in PC-12 Cells: Effects of H3 Receptor-Inspired Electromagnetic Fields and Inherent Schumann Frequencies PC-12 细胞的神经元生长和电活动:H3 受体激发的电磁场和固有舒曼频率的影响
Pub Date : 2024-02-07 DOI: 10.3390/biophysica4010005
Landon M. Lefebvre, Adam D. Plourde-Kelly, K. Saroka, B. Dotta
Cells are continually exposed to a range of electromagnetic fields (EMFs), including those from the Schumann resonance to radio waves. The effects of EMFs on cells are diverse and vary based on the specific EMF type. Recent research suggests potential therapeutic applications of EMFs for various diseases. In this study, we explored the impact of a physiologically patterned EMF, inspired by the H3 receptor associated with wakefulness, on PC-12 cells in vitro. Our hypothesis posited that the application of this EMF to differentiated PC-12 cells could enhance firing patterns at specific frequencies. Cell electrophysiology was assessed using a novel device, allowing the computation of spectral power density (SPD) scores for frequencies between 1 Hz and 128 Hz. T-tests comparing SPD at certain frequencies (e.g., 29 Hz, 30 Hz, and 79 Hz) between the H3-EMF and control groups showed a significantly higher SPD in the H3 group (p < 0.050). Moreover, at 7.8 Hz and 71 Hz, a significant correlation was observed between predicted and percentages of cells with neurites (R = 0.542). Key findings indicate the efficacy of the new electrophysiology measure for assessing PC-12 cell activity, a significant increase in cellular activity with the H3-receptor-inspired EMF at specific frequencies, and the influence of 7.8 Hz and 71 Hz frequencies on neurite growth. The overall findings support the idea that the electrical frequency profiles of developing cell systems can serve as an indicator of their progression and eventual cellular outcomes.
细胞持续暴露于各种电磁场(EMF),包括从舒曼共振到无线电波的电磁场。电磁场对细胞的影响多种多样,并根据具体的电磁场类型而有所不同。最近的研究表明,电磁场具有治疗各种疾病的潜力。在本研究中,我们探讨了生理模式电磁场对体外 PC-12 细胞的影响,这种电磁场受与觉醒相关的 H3 受体的启发。我们的假设是,将这种电磁场应用于分化的 PC-12 细胞可增强特定频率的发射模式。细胞电生理学评估采用了一种新型设备,可计算出 1 赫兹到 128 赫兹频率的频谱功率密度 (SPD) 分数。对 H3-EMF 组和对照组在某些频率(如 29 Hz、30 Hz 和 79 Hz)的 SPD 进行 T 检验,结果显示 H3 组的 SPD 明显更高(p < 0.050)。此外,在 7.8 Hz 和 71 Hz 时,预测值与神经元细胞百分比之间存在显著相关性(R = 0.542)。主要研究结果表明,新的电生理学测量方法可有效评估 PC-12 细胞的活性,在特定频率下,受 H3 受体启发的电磁场可显著提高细胞活性,而且 7.8 赫兹和 71 赫兹的频率对神经元生长有影响。总体研究结果支持这样一种观点,即发育中细胞系统的电频率曲线可作为其进展和最终细胞结果的指标。
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引用次数: 0
Bioprinting of Hydrogel-Based Drug Delivery Systems for Nerve Tissue Regeneration 用于神经组织再生的水凝胶生物打印给药系统
Pub Date : 2024-01-31 DOI: 10.3390/biophysica4010004
Eliza Marie Steele, Zacheus L. Carr, E. Dosmar
Globally, thousands of people are affected by severe nerve injuries or neurodegenerative disorders. These conditions cannot always be cured because nerve tissue either does not regenerate or does so at a slow rate. Therefore, tissue engineering has emerged as a potential treatment approach. This review discusses 3D bioprinting for scaffold manufacturing, highlights the advantages and disadvantages of common bioprinting techniques, describes important considerations for bioinks, biomaterial inks, and scaffolds, and discusses some drug delivery systems. The primary goal of this review is to bring attention to recent advances in nerve tissue engineering and its possible clinical applications in peripheral nerve, spinal cord, and cerebral nerve regeneration. Only studies that use 3D bioprinting or 3D printing to manufacture hydrogel scaffolds and incorporate the sustained release of a drug or growth factor for nerve regeneration are included. This review indicates that 3D printing is a fast and precise scaffold manufacturing technique but requires printing materials with specific properties to be effective in nervous tissue applications. The results indicate that the sustained release of certain drugs and growth factors from scaffolds can significantly improve post-printing cell viability, cell proliferation, adhesion, and differentiation, as well as functional recovery compared with scaffolds alone. However, more in vivo research needs to be conducted before this approach can be used in clinical applications.
全球有成千上万的人受到严重神经损伤或神经退行性疾病的影响。由于神经组织无法再生或再生速度缓慢,这些疾病并不总是可以治愈。因此,组织工程已成为一种潜在的治疗方法。本综述讨论了用于支架制造的三维生物打印技术,强调了常见生物打印技术的优缺点,介绍了生物墨水、生物材料墨水和支架的重要注意事项,并讨论了一些给药系统。本综述的主要目的是让人们关注神经组织工程的最新进展及其在周围神经、脊髓和脑神经再生方面可能的临床应用。只有使用三维生物打印或三维打印技术制造水凝胶支架并结合药物或生长因子的持续释放以促进神经再生的研究才被纳入其中。这篇综述指出,三维打印是一种快速、精确的支架制造技术,但需要打印材料具有特定的特性,才能在神经组织应用中有效。研究结果表明,与单独使用支架相比,从支架中持续释放某些药物和生长因子可显著提高打印后细胞的存活率、细胞增殖、粘附和分化能力以及功能恢复能力。不过,在将这种方法用于临床应用之前,还需要进行更多的体内研究。
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引用次数: 0
Supercriticality, Glassy Dynamics, and the New Insight into Melting/Freezing Discontinuous Transition in Linseed Oil 超临界性、玻璃态动力学以及亚麻籽油熔融/冷冻不连续转变的新发现
Pub Date : 2024-01-23 DOI: 10.3390/biophysica4010003
A. Drozd-Rzoska, S. Rzoska, J. Łoś
The long-range supercritical changes of dielectric constant, resembling ones observed in the isotropic liquid phase of liquid crystalline compounds, are evidenced for linseed oil—although in the given case, the phenomenon is associated with the liquid–solid melting/freezing discontinuous phase transitions. This ‘supercriticality’ can be an additional factor supporting the unique pro-health properties of linseed oil. Broadband dielectric spectroscopy studies also revealed the ‘glassy’ changes of relaxation times, well portrayed by the ‘activated and critical’ equation recently introduced. In the solid phase, the premelting effect characteristic for the canonic melting/freezing discontinuous transition, i.e., without any pretransitional effect in the liquid phase, has been detected. It is interpreted within the grain model, and its parameterization is possible using the Lipovsky model and the ‘reversed’ Mossotti catastrophe concept. For the premelting effect in the solid state, the singular ‘critical’ temperature correlates with the bulk discontinuous melting and freezing temperatures. Consequently, the report shows that linseed oil, despite its ‘natural and complex’ origins, can be considered a unique model system for two fundamental problems: (i) pretransitional (supercritical) effects in the liquid state associated with a weakly discontinuous phase transition, and (ii) the premelting behavior in the solid side of the discontinuous melting/freezing discontinuous transition.
亚麻籽油的介电常数发生了长程超临界变化,这种变化类似于在液晶化合物的各向同性液相中观察到的变化。这种 "超临界性 "可能是亚麻籽油具有独特保健特性的另一个因素。宽带介电光谱研究也揭示了弛豫时间的 "玻璃化 "变化,最近引入的 "活化和临界 "方程很好地描绘了这一变化。在固相中,检测到了卡农式熔化/冷冻不连续转变所特有的预熔化效应,即在液相中没有任何预转变效应。它在晶粒模型中得到了解释,并可以利用利波夫斯基模型和 "反向 "莫索蒂灾难概念对其进行参数化。对于固态中的预熔化效应,奇异的 "临界 "温度与块体的不连续熔化和冻结温度相关。因此,报告显示,尽管亚麻籽油的起源 "天然而复杂",但它可以被视为两个基本问题的独特模型系统:(i) 与弱不连续相变相关的液态预过渡(超临界)效应,以及 (ii) 不连续熔化/冻结不连续相变固态侧的预熔化行为。
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引用次数: 0
The Effect of UV-Vis Radiation on DNA Systems Containing the Photosensitizers Methylene Blue and Acridine Orange 紫外可见光辐射对含有光敏剂亚甲基蓝和吖啶橙的 DNA 系统的影响
Pub Date : 2024-01-12 DOI: 10.3390/biophysica4010002
Thais P. Pivetta, Paulo A. Ribeiro, M. Raposo
As a vital biomolecule, DNA is known as a target of antineoplastic drugs for cancer therapy. These drugs can show different modes of interaction with DNA, with intercalation and groove binding being the most common types. The intercalation of anticancer drugs with DNA can lead to the disruption of its normal function, influencing cell proliferation. Methylene blue (MB) and acridine orange (AO) are examples of DNA-intercalating agents that have been studied for their application against some types of cancer, mainly for photodynamic therapy. In this work, the impact of light irradiation on these compounds in the absence and presence of DNA was analyzed by means of UV-vis spectroscopy. Bathochromic and hypochromic shifts were observed in the absorbance spectra, revealing the intercalation of the dyes with the DNA base pairs. Dyes with and without DNA present different profiles of photodegradation, whereby the dyes alone were more susceptible to degradation. This can be justified by the intercalation of the dyes on the DNA base pairs allowing the DNA molecule to partially hinder the molecules’ exposition and, therefore, reducing their degradation.
作为一种重要的生物大分子,DNA 是抗肿瘤药物治疗癌症的靶点。这些药物与 DNA 的相互作用方式各不相同,其中最常见的是插层作用和沟结合作用。抗癌药物与 DNA 的插层作用会破坏 DNA 的正常功能,影响细胞增殖。亚甲基蓝(MB)和吖啶橙(AO)就是 DNA 插层剂的例子,它们已被研究用于抗击某些类型的癌症,主要是光动力疗法。在这项工作中,我们通过紫外可见光谱分析了在 DNA 不存在和存在的情况下,光照射对这些化合物的影响。在吸光度光谱中观察到了双色和低色偏移,揭示了染料与 DNA 碱基对的插层作用。含 DNA 和不含 DNA 的染料呈现出不同的光降解特征,其中单独的染料更容易降解。这是因为染料插层在 DNA 碱基对上,使 DNA 分子部分阻碍了分子的暴露,从而减少了降解。
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引用次数: 0
期刊
Biophysica
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