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Radiation-induced alterations in the dielectric features of irradiated tissues 辐照组织介电特性的辐射诱导改变
IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-04-29 DOI: 10.1016/j.bpc.2025.107452
Abdelrazek B. Abdelrazzak , Fawzy G. El Desouky
In this study, we investigated the dielectric characteristics of the brain, lung heart, liver, spleen and kidney that were either directly irradiated or were abscopal to the irradiated region, in an attempt to utilize the physical tool of dielectric spectroscopy to identify the biological effects of ionizing radiation. The dielectric analyses were performed for 1–2 mm thick freeze-dried samples, of the different organs, sandwiched between two brass electrodes at room temperature in the frequency range 0.1–107 Hz. The results show notable modifications in the dielectric properties of the liver of the whole body irradiated group (WB) and the kidney of lower-limb (LL) and cranially (CR) irradiated groups. The data show increase in the imaginary electric modulus M and decrease in the permittivity and AC conductivity in the heart and brain of all of the irradiated groups. The data show a general trend of increase in the conductivity of the liver of WB and the kidney of CR and LL groups. The Cole-Cole plot (M vs. M), as a good depiction of the dielectric behavior of the tissues, show differential response of the different organs. The expansion of loss tangent peaks indicates relaxation dispersion with a steady relaxation time distribution for the liver, kidney and lung. The extended relaxation periods and frequency shifts to lower values results indicate variation in the rigidity of biological macromolecules in the liver, lung and kidney only. The experimental data suggest induction of abscopal effect occur in the liver, kidney, lung than heart, brain and spleen.
在本研究中,我们研究了脑、肺、心、肝、脾和肾直接或离辐照区域的介电特性,试图利用介电光谱的物理工具来识别电离辐射的生物效应。在0.1-107 Hz的频率范围内,对不同器官的1-2 mm厚的冻干样品在室温下夹在两个黄铜电极之间进行介电分析。结果表明,全身照射组(WB)肝脏、下肢照射组(LL)和颅脑照射组(CR)肾脏的介电特性有明显改变。数据显示,所有辐照组心脏和大脑的虚电模量M”增加,介电常数和交流电导率下降。数据显示,WB组的肝脏和CR、LL组的肾脏电导率均有增加的趋势。Cole-Cole图(M′vs. M′)很好地描述了组织的介电行为,显示了不同器官的差异响应。损失切线峰的扩大表明松弛色散,肝、肾和肺的松弛时间分布稳定。松弛期的延长和频率向低值移动的结果表明,生物大分子的刚性只在肝、肺和肾中发生变化。实验数据表明,肝、肾、肺比心、脑和脾更能诱导体外效应。
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引用次数: 0
Interaction process behind the strong stabilization of G-quadruplexes by alkaloid fagaronine 生物碱法加隆碱强稳定 G-四链体的相互作用过程
IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-04-15 DOI: 10.1016/j.bpc.2025.107443
Pavel Hannig , Raimundo Gargallo , Stefania Mazzini , Gigliola Borgonovo , Marco Zuccolo , Eva Táborská , Petr Táborský
Benzo[c]phenanthridine alkaloids are known for their stabilizing effects on non-canonical DNA structures, particularly G-quadruplexes (G4s). In this study, the interaction of fagaronine, a rare benzo[c]phenanthridine alkaloid, with several DNA structures (including B-DNA, parallel, antiparallel and hybrid G4s) is studied using molecular fluorescence and circular dichroism (CD) spectroscopy. It has been found that fagaronine significantly enhances the stability of all tested G4 conformations. Furthermore, a study by NMR spectroscopy provided valuable information on the mechanism of interaction of the ligand with the parallel G4 structure adopted by Pu22T14T23, a sequence mutated with respect to that found within the promoter region of the c-myc gene. Remarkably, when compared with data reported in the literature, fagaronine appears to exhibit one of the strongest G4 thermal stabilization effects ever recorded for a small ligand.
苯并[c]菲蒽啶生物碱因其对非典型DNA结构的稳定作用而闻名,特别是g -四聚体(G4s)。本研究利用分子荧光和圆二色性(CD)光谱研究了一种罕见的苯并[c]菲蒽啶生物碱fagaronine与几种DNA结构(包括B-DNA、平行、反平行和杂交G4s)的相互作用。研究发现,fagaronine显著提高了所有测试的G4构象的稳定性。此外,核磁共振波谱研究提供了配体与Pu22T14T23所采用的平行G4结构相互作用机制的宝贵信息,Pu22T14T23是在c-myc基因启动子区域内发现的一个突变序列。值得注意的是,与文献中报道的数据相比,fagaronine似乎表现出有史以来对小配体最强的G4热稳定效应之一。
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引用次数: 0
Green synthesis, characterization, structural, morphological, antibacterial, and cytotoxicity evaluation of zinc oxide nanoparticles using Fioria vitifolia extract 绿色合成、表征、结构、形态、抗菌和细胞毒性评价的氧化锌纳米颗粒
IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-04-10 DOI: 10.1016/j.bpc.2025.107440
A. Nandhini , P. Anilkumar , J. Jasmin , S. Balamurali
The increasing prevalence of bacterial pathogens diseases and the rise in multidrug resistance highlights the urgent need for new drug delivery systems or novel drug molecules to enhance treatment options. Zinc oxide (ZnO) nanoparticles attracting attention due to their potential in biomedical applications, such as cancer therapy and diagnostics. ZnO is a versatile compound with excellent UV-blocking, anti-inflammatory, and wide-bandgap semiconductor properties. This study focuses on the green synthesis of ZnO nanoparticles using ‘Fioria vitifolia’ leaf extract, as a reducing agent with polyvinylpyrrolidone (PVP) aids in reducing particle size and preventing aggregation, enhancing nanoparticle stability. The ZnO nanoparticles were characterized using various techniques, including X-ray diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM), Energy-Dispersive X-ray Analysis (EDX), Transmission Electron Microscopy (TEM), Fourier-Transform Infrared Spectroscopy (FTIR), UV–Vis Diffuse Reflectance Spectroscopy (DRS), and Photoluminescence (PL). These analyses confirmed the successful formation of ZnO nanoparticles. The nanoparticles demonstrated strong antimicrobial activity, especially against ‘Enterobacter’, and exhibited significant cytotoxic effects on lung cancer cells (A549), but has low toxicity to standard cells (L929). The IC50 values affirmed their potential as anticancer agents, suggesting their dual promise as antimicrobial and anticancer compounds. The enormous potential of biosynthesized ZnO nanoparticles as biological agents a sustainable substitute for chemically synthesized medications is highlighted in this study. The potential of the nanoparticles in a range of biomedical applications is highlighted by their ecologically friendly manufacturing process as well as their proven antibacterial and anticancer qualities.
细菌性病原体疾病的日益流行和多药耐药性的增加突出表明迫切需要新的药物输送系统或新的药物分子来加强治疗选择。氧化锌纳米颗粒因其在癌症治疗和诊断等生物医学领域的潜在应用而备受关注。ZnO是一种多功能化合物,具有优异的抗紫外线、抗炎和宽禁带半导体特性。本研究主要研究了以“红叶”叶提取物为还原剂,以聚乙烯吡咯烷酮(PVP)为还原剂,绿色合成ZnO纳米颗粒,有助于减小粒径和防止团聚,提高纳米颗粒的稳定性。采用x射线衍射(XRD)、场发射扫描电子显微镜(FESEM)、能量色散x射线分析(EDX)、透射电子显微镜(TEM)、傅里叶变换红外光谱(FTIR)、紫外-可见漫反射光谱(DRS)和光致发光(PL)等多种技术对ZnO纳米颗粒进行了表征。这些分析证实了ZnO纳米颗粒的成功形成。纳米颗粒显示出很强的抗菌活性,特别是对肠杆菌,并对肺癌细胞(A549)显示出显著的细胞毒性作用,但对标准细胞(L929)具有低毒性。IC50值肯定了它们作为抗癌药物的潜力,表明它们作为抗菌和抗癌化合物的双重前景。本研究强调了生物合成ZnO纳米颗粒作为生物制剂的巨大潜力,它是化学合成药物的可持续替代品。纳米颗粒在一系列生物医学应用中的潜力是由其生态友好的制造过程以及经证实的抗菌和抗癌特性所突出的。
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引用次数: 0
Degree–based topological indices, NMR chemical shifts, chemical reactivity, molecular dynamics and DFT analysis of 1,4-Methanoazulene-9-methanol, Decahydro-4,8,8-trimethyl-, [1S-(1α,3aβ,4α,8aβ,9R)] 1,4-Methanoazulene-9-methanol, Decahydro-4,8,8-trimethyl-, [1S-(1α,3aβ,4α,8aβ,9R)] 的基于度的拓扑指数、核磁共振化学位移、化学反应活性、分子动力学和 DFT 分析
IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-04-09 DOI: 10.1016/j.bpc.2025.107442
Jeffrin JA Laura , P. Rajesh , M. Kesavan , E. Dhanalakshmi , S. Kayashrini , M. Prabhaharan
This study aims to comprehensively analyze the structural, vibrational, and electrical characteristics of 11,4-Methanoazulene-9-methanol, decahydro-4,8,8-trimethyl-, [1S-(1α,3aβ,4α,8aβ,9R*)] (MMDT) with a focus on its potential as a therapeutic agent for liver cancer. The compound was isolated from Hybanthus enneaspermus using Soxhlet extraction, followed by Gas Chromatography-Mass Spectrometry (GC–MS) analysis. The structure optimization and vibrational frequency assignments were done using Density Functional Theory (DFT) method with the B3LYP/6–311++G (d, p) basis set. Natural Bond Orbital (NBO) analysis was conducted to explore intramolecular and intermolecular interactions, along with the first-order hyperpolarizability. Electronic properties such as the energy gap and molecular electrostatic potential (MEP), were calculated to anticipate reactive sites for electrophilic and nucleophilic attacks. This is crucial in understanding the compound's reactivity in biological systems. TD-DFT was employed to simulate UV–visible spectra and compared with experimental values. Additionally, the theoretical FTIR spectra were correlated with experimental data, with potential energy distribution (PED%) providing detailed vibrational mode analysis. HOMO and LUMO orbitals were evaluated in the gas phase, revealing key energy parameters. 1H and 13C NMR chemical shifts have been properly assigned using the DFT for structural characterization. QSPR/QSAR analysis is made simpler by determining a few topological indices for the MMDT. This study provides a novel computational framework for MMDT paving the way for faster, cost-effective and the Molecular docking studies revealed stable interactions between MMDT and liver cancer-related receptors, with favourable binding energy values along with Ramachandran plot confirmed the stability of the protein-ligand complex could be a promising candidate for liver cancer treatment.
本研究旨在全面分析11,4-甲烷偶氮烯-9-甲醇,十氢-4,8,8-三甲基- [1S-(1α,3aβ,4α,8aβ,9R*)] (MMDT)的结构、振动和电学特性,重点研究其作为肝癌治疗剂的潜力。采用索氏提取法从棘豆中分离得到该化合物,并采用气相色谱-质谱联用技术对其进行分析。采用密度泛函理论(DFT)方法,以B3LYP/ 6-311 ++G (d, p)基集对结构进行优化和振动频率赋值。利用自然键轨道(NBO)分析了分子内和分子间的相互作用,以及一阶超极化率。通过计算能隙和分子静电势(MEP)等电子性质来预测亲电和亲核攻击的反应位点。这对于理解化合物在生物系统中的反应性至关重要。采用TD-DFT模拟紫外可见光谱,并与实验值进行比较。此外,理论FTIR光谱与实验数据相关联,势能分布(PED%)提供了详细的振动模式分析。在气相中对HOMO和LUMO轨道进行了评估,揭示了关键的能量参数。1H和13C核磁共振化学位移已适当分配使用DFT结构表征。通过确定MMDT的几个拓扑指标,使QSPR/QSAR分析变得更简单。这项研究为MMDT提供了一个新的计算框架,为更快、更经济地实现MMDT铺平了道路。分子对接研究揭示了MMDT与肝癌相关受体之间稳定的相互作用,有利的结合能值和Ramachandran图证实了蛋白质-配体复合物的稳定性,可能是肝癌治疗的有希望的候选者。
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引用次数: 0
Receptor modulated assembly and drug induced disassembly of amyloid beta aggregates at asymmetric neuronal model biomembranes 受体调节的β淀粉样蛋白聚集体在不对称神经元模型生物膜上的组装和药物诱导的拆卸
IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-31 DOI: 10.1016/j.bpc.2025.107441
Nirod Kumar Sarangi , Subrata Mondal , Tia E. Keyes
Amyloid peptide non-fibrillar oligomers cause neurotoxicity and may contribute to Alzheimer's disease (AD) pathogenesis. Mounting evidence indicates that Aβ1–42 oligomers disrupt and remodel neuronal membrane, causing neuronal cell death. The involvement of individual neuronal membrane constituents in real-time Aβ1–42 aggregate assembly is unclear due to complexity of neuronal cell membrane. We used non-Faradaic electrochemical impedance spectroscopy (EIS) to track monomeric Aβ1–42 peptide binding and aggregation pathways in real-time in asymmetric micropore suspended lipid bilayer membranes with anionic phospholipids and glycosphingolipids. Anionic DOPC:PIP2 pore suspended membrane showed pore-formation within 2 h of incubation, but peptide insertion occurred over 6 h, with an onset time of ∼6–8 h for peptide aggregation at the membrane surface. Among different gangliosides, peptide binding to GM1- and GM3-containing membranes did not result pore development, but receptor mediated peptide aggregation formation caused membrane admittance to decrease within 2 h. In contrast, partial peptide insertion in the membrane surface increases membrane admittance at GD1a and mixed GSL membranes, arresting aggregation. Time-lapsed AFM imaging at asymmetric solid supported lipid bilayers (aSLBs) corroborated EIS findings, capturing pore-formation and receptor mediated peptide assembly routes. Fluorescence lifetime imaging (FLIM) imaging and spatial resolved single-point fluorescence correlation spectroscopy (FCS) at aSLBs revealed membrane-peptide interaction, assembly, and peptide induced membrane reorganization. Treatment with antidepressants fluoxetine and imipramine therapeutics, in synergy, which are cost-effective and capable of crossing the central nervous system (CNS+), resulted in the disassembly of membrane mediated Aβ1–42 aggregates, but not fibrils. Overall, the data suggests that membrane-mediated aggregate disassembly at the correct timing of AD progression may halt or reverse amyloid assembly through the use of repurposed drugs.
淀粉样肽非纤维低聚物引起神经毒性,并可能有助于阿尔茨海默病(AD)的发病机制。越来越多的证据表明,Aβ1-42寡聚物破坏和重塑神经元膜,导致神经元细胞死亡。由于神经元细胞膜的复杂性,单个神经元膜成分参与实时Aβ1-42聚集体的组装尚不清楚。利用非法拉第电化学阻抗谱(EIS)实时跟踪了含有阴离子磷脂和鞘糖脂的不对称微孔悬浮脂质双层膜中单体Aβ1-42肽的结合和聚集途径。阴离子DOPC:PIP2孔悬浮膜在2小时内形成孔,但在6小时内发生肽插入,肽在膜表面聚集的开始时间为~ 6 - 8小时。在不同的神经节苷类中,肽与含GM1-和含gm3的膜结合不导致孔发育,但受体介导的肽聚集形成导致膜导纳在2小时内降低。相反,部分肽在膜表面的插入增加了GD1a和混合GSL膜的膜导纳,阻止了聚集。非对称固体支撑脂质双分子层(aSLBs)的延时AFM成像证实了EIS的发现,捕获了孔隙形成和受体介导的肽组装途径。aSLBs的荧光寿命成像(FLIM)和空间分辨单点荧光相关光谱(FCS)揭示了膜-肽的相互作用、组装和肽诱导的膜重组。抗抑郁药氟西汀和丙咪嗪治疗协同作用,具有成本效益,能够穿过中枢神经系统(CNS+),导致膜介导的Aβ1-42聚集体的分解,但不破坏原纤维。总的来说,这些数据表明,在AD进展的正确时间,膜介导的聚集体分解可以通过使用重新定位的药物来停止或逆转淀粉样蛋白的组装。
{"title":"Receptor modulated assembly and drug induced disassembly of amyloid beta aggregates at asymmetric neuronal model biomembranes","authors":"Nirod Kumar Sarangi ,&nbsp;Subrata Mondal ,&nbsp;Tia E. Keyes","doi":"10.1016/j.bpc.2025.107441","DOIUrl":"10.1016/j.bpc.2025.107441","url":null,"abstract":"<div><div>Amyloid peptide non-fibrillar oligomers cause neurotoxicity and may contribute to Alzheimer's disease (AD) pathogenesis. Mounting evidence indicates that Aβ<sub>1–42</sub> oligomers disrupt and remodel neuronal membrane, causing neuronal cell death. The involvement of individual neuronal membrane constituents in real-time Aβ<sub>1–42</sub> aggregate assembly is unclear due to complexity of neuronal cell membrane. We used non-Faradaic electrochemical impedance spectroscopy (EIS) to track monomeric Aβ<sub>1–42</sub> peptide binding and aggregation pathways in real-time in asymmetric micropore suspended lipid bilayer membranes with anionic phospholipids and glycosphingolipids. Anionic DOPC:PIP2 pore suspended membrane showed pore-formation within 2 h of incubation, but peptide insertion occurred over 6 h, with an onset time of ∼6–8 h for peptide aggregation at the membrane surface. Among different gangliosides, peptide binding to GM1- and GM3-containing membranes did not result pore development, but receptor mediated peptide aggregation formation caused membrane admittance to decrease within 2 h. In contrast, partial peptide insertion in the membrane surface increases membrane admittance at GD1a and mixed GSL membranes, arresting aggregation. Time-lapsed AFM imaging at asymmetric solid supported lipid bilayers (aSLBs) corroborated EIS findings, capturing pore-formation and receptor mediated peptide assembly routes. Fluorescence lifetime imaging (FLIM) imaging and spatial resolved single-point fluorescence correlation spectroscopy (FCS) at aSLBs revealed membrane-peptide interaction, assembly, and peptide induced membrane reorganization. Treatment with antidepressants fluoxetine and imipramine therapeutics, in synergy, which are cost-effective and capable of crossing the central nervous system (CNS+), resulted in the disassembly of membrane mediated Aβ<sub>1–42</sub> aggregates, but not fibrils. Overall, the data suggests that membrane-mediated aggregate disassembly at the correct timing of AD progression may halt or reverse amyloid assembly through the use of repurposed drugs.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"322 ","pages":"Article 107441"},"PeriodicalIF":3.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Interaction of Myrsinoic acid a with biomembrane models: Differential effects on DPPC and DPPS properties revealed by surface rheology and vibrational spectroscopy 蜜桃酸a与生物膜模型的相互作用:通过表面流变学和振动光谱揭示对DPPC和DPPS性能的差异影响
IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-28 DOI: 10.1016/j.bpc.2025.107439
Ana Gabrieli A. dos Santos, Fernando Cassas, Kevin Figueiredo dos Santos, Livia Soman de Medeiros, Thiago André Moura Veiga, Luciano Caseli
This study investigates the interactions of Myrsinoic acid A, a natural compound with reported anti-inflammatory and antitumor properties, with lipid monolayers composed of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylserine (DPPS). Utilizing tensiometry, polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS), Brewster Angle Microscopy (BAM), and surface rheology, we analyzed how Myrsinoic acid A affects the structural and mechanical properties of these lipid systems. The PM-IRRAS spectra revealed that Myrsinoic acid A induced disorder in the DPPC monolayer, shifting CH₂ asymmetric stretching peaks and decreasing packing order, while DPPS remained structurally stable. Surface rheology measurements showed reduced elasticity in both lipids, with differential effects on viscosity: a decrease for DPPC and an increase for DPPS, indicating varied molecular interactions. BAM images confirmed that DPPC maintained a homogeneous morphology, while DPPS displayed aggregate formation, suggesting distinct lipid-drug interactions. These findings highlight the importance of lipid composition in modulating the effects of Myrsinoic acid A on membrane properties, providing insights into its potential therapeutic applications in targeting tumorigenic versus non-tumorigenic cells.
本研究研究了具有抗炎和抗肿瘤特性的天然化合物桃金酸A与双棕榈酰磷脂酰胆碱(DPPC)和双棕榈酰磷脂酰丝氨酸(DPPS)组成的脂质单分子膜的相互作用。利用张力测定法、偏振调制红外反射吸收光谱(PM-IRRAS)、Brewster角度显微镜(BAM)和表面流变学,我们分析了桃金酸A如何影响这些脂质系统的结构和力学性能。PM-IRRAS光谱显示,桃金酸A导致DPPC单层结构紊乱,ch2不对称拉伸峰移位,堆积顺序降低,而DPPS结构保持稳定。表面流变学测量表明,两种脂类的弹性都降低了,对粘度的影响不同:DPPC降低,DPPS增加,表明不同的分子相互作用。BAM图像证实DPPC保持均匀形态,而DPPS显示聚集形成,表明明显的脂质-药物相互作用。这些发现强调了脂质组成在调节桃金酸A对膜特性的影响中的重要性,为其针对致瘤细胞和非致瘤细胞的潜在治疗应用提供了见解。
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引用次数: 0
Phenolic fractions of Heliotropium Bacciferum inhibit human insulin aggregation and protect against amyloid-induced cytotoxicity: Structural and biophysical analysis Heliotropium Bacciferum的酚类组分抑制人胰岛素聚集和防止淀粉样蛋白诱导的细胞毒性:结构和生物物理分析
IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-27 DOI: 10.1016/j.bpc.2025.107437
Moneera Saud Al-Bagmi , Majed S. Alokail , Nasser M. Al-Daghri , Nojood Altwaijry , Ibrahim M. Aziz , Fahad N. Almajhdi , Mohd Shahnawaz Khan
In humans, more than 50 diseases are related to protein fibrillation, including Alzheimer's and Parkinson's diseases. Inhibition of amyloid fibril formation using natural products is one of the main therapeutic strategies for preventing the progression of these diseases. In this context, phenolic extract fractions from Heliotropium bacciferum leaves were evaluated for their ability to inhibit the aggregation of human insulin (HI), an appropriate model protein for fibrillation under physiological conditions and agitation at 600 rpm. Our results exhibited HI fibrillation under studied conditions, with aggregation kinetic fitting a sigmoidal curve with tlag and kapp values of 44.4 h and 0.16 h−1, respectively. Structural changes preceding the onset of fibril formation were detected by 8-Anilino-1-naphthalene-sulphonic acid (ANS) probe, revealed the exposure of hydrophobic regions in the HI peptide to the solvent, with tlag and kapp values of 18.2 h 0.12 h−1, respectively. CD spectroscopy calculated the formed fibrils comprised of 51.6 % β-sheet structure and 43.0 % unordered structure. In vitro studies demonstrated a dose-dependent inhibitory effect of H. bacciferum extracts on HI fibrillation. The free phenolic fraction (FPF) at 200 μg/mL exhibited nearly complete inhibition, whereas the bound phenolic fraction (BPF) demonstrated a 52 % reduction in fibrillation. These findings were further validated using Rayleigh light scattering (RLS) and circular dichroism analyses. Transmission electron microscopy (TEM) validated the formation of insulin fibrillation and its inhibition by extract fractions. Moreover, MTT assay results on SH-SY5Y cells showed that both extract fractions attenuated HI fibril-induced neuronal toxicity in a dose-dependent manner. Furthermore, RT-PCR analysis revealed that co-treatment with a low concentration (7.8 μg/mL) of H. bacciferum extracts led to a significant reduction in the expression levels of pro-apoptotic genes (Casp3 and Bax) and an increase in the anti-apoptotic gene Bcl-2 in SH-SY5Y cells treated with fibrillated HI. This study highlights the potential of H. bacciferum extracts as therapeutic agents against protein fibrillation-related diseases and underscores the importance of polyphenols in preventing amyloid fibril formation.
在人类中,有50多种疾病与蛋白质纤颤有关,包括阿尔茨海默病和帕金森病。使用天然产物抑制淀粉样蛋白纤维的形成是预防这些疾病进展的主要治疗策略之一。在这种情况下,从Heliotropium bacciferum叶片中提取的酚类提取物被评估其抑制人胰岛素(HI)聚集的能力,HI是生理条件下纤维性颤动的合适模型蛋白,在600转/分的搅拌下。我们的研究结果显示,在研究条件下,HI纤颤的聚集动力学符合s型曲线,其标志和kapp值分别为44.4 h和0.16 h−1。通过8-苯胺-1-萘磺酸(ANS)探针检测纤维形成前的结构变化,发现HI肽中的疏水区暴露于溶剂中,其标记值和kapp值分别为18.2 h 0.12 h−1。CD谱计算出形成的原纤维由51.6%的β片结构和43.0%的无序结构组成。体外研究表明,芽孢杆菌提取物对HI纤颤有剂量依赖性的抑制作用。200 μg/mL的游离酚组分(FPF)表现出几乎完全的抑制作用,而结合酚组分(BPF)显示出52%的纤颤减少。使用瑞利光散射(RLS)和圆二色性分析进一步验证了这些发现。透射电镜(TEM)证实了胰岛素纤颤的形成及其提取物的抑制作用。此外,SH-SY5Y细胞的MTT实验结果显示,两种提取物都以剂量依赖的方式减弱了HI原纤维诱导的神经元毒性。此外,RT-PCR分析显示,低浓度(7.8 μg/mL) H. bacciferum提取物共处理SH-SY5Y细胞后,促凋亡基因Casp3和Bax的表达水平显著降低,抗凋亡基因Bcl-2的表达水平显著升高。本研究强调了芽孢杆菌提取物作为治疗蛋白纤颤相关疾病的潜力,并强调了多酚在预防淀粉样纤维形成中的重要性。
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引用次数: 0
The amyloidogenic peptide stretch in human tau, tau306–311 is a promising injectable hydrogelator 人tau蛋白中的淀粉样蛋白肽片段tau306-311是一种很有前途的注射用凝胶剂
IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-24 DOI: 10.1016/j.bpc.2025.107438
Shubhangini Singh Verma, Shinjini Bhattacharya, Sachin Kumar, Nitin Chaudhary
A vast majority of peptide hydrogelators harbor a bulky, non-native aromatic moiety. Such foreign moieties raise safety concerns as far as biomedical applications of hydrogels are concerned. The hydrogel research, therefore, has branched to another dimension – to identify native or native-like short peptide stretches that could cause the gelation of biological fluids. Using well-defined criteria to identify native peptide stretches that could form a viscous solution in water but cause gelation of phosphate-buffered saline (PBS), we identified the hexapeptide stretch from human tau, viz. tau306–311, as a promising injectable hydrogelator. The peptide causes instant gelation of PBS and the cell culture media. Such hydrogels find applications as drug delivery vehicles, scaffolds for mammalian cell culture, wound-dressing material, etc.
绝大多数肽凝胶都含有大量非天然的芳香基团。就水凝胶的生物医学应用而言,这些外国成分引起了安全问题。因此,水凝胶研究已经扩展到另一个维度——识别可能导致生物液体凝胶化的天然或类似于天然的短肽延伸。使用定义明确的标准来鉴定天然肽段,这些肽段可以在水中形成粘性溶液,但会导致磷酸盐缓冲盐水(PBS)凝胶化,我们鉴定了来自人类tau蛋白的六肽段,即tau306-311,作为一种有前途的可注射凝胶剂。肽使PBS和细胞培养基瞬间凝胶化。这种水凝胶可以应用于药物输送载体、哺乳动物细胞培养支架、伤口敷料等。
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引用次数: 0
Characterization of metabolism associated with outcomes in severe acute pancreatitis: Insights from serum metabolomic analysis 代谢与重症急性胰腺炎预后相关的特征:来自血清代谢组学分析的见解
IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-15 DOI: 10.1016/j.bpc.2025.107436
Mohd Adnan Siddiqui , Anamika Singh , Swarnima Pandey , Mohammed Haris Siddiqui , Afzal Azim , Neeraj Sinha
Severe Acute Pancreatitis (SAP) is characterized by an abrupt onset of pancreatic inflammation, which may induce damage to other organs, and is associated with significant morbidity and mortality. Despite the considerable disease burden, specific treatments to stop progression or prevent occurrence are limited. Currently, there is a paucity of comprehensive studies that thoroughly explore metabolic dysregulation in SAP, particularly those that emphasize changes in outcomes. Nuclear magnetic resonance (NMR) based metabolomics coupled with multivariate analysis was applied to serum samples of 20 survivors and 30 non-survivors of SAP to identify metabolic changes linked to different outcomes. The discriminant analysis of serum samples of SAP survivors and non-survivors revealed isoleucine, leucine, valine, arginine, lactate, and 3-hydroxybutyrate as significant metabolites elevated in the non-survivors. These identified metabolites had shown a significant positive correlation with clinical severity scores in the Pearson correlation analysis. Pathway analysis revealed disruptions in amino acid metabolism, driven by protein catabolism to fulfill the patient's energy requirements. This study highlights the importance of metabolomics in unraveling the molecular and physiological mechanisms underlying SAP. These findings offer valuable insights for clinicians to develop treatment strategies that target metabolic pathways in SAP, potentially for improving patient outcomes.
严重急性胰腺炎(SAP)的特点是胰腺炎症的突然发作,可引起其他器官的损害,并与显著的发病率和死亡率相关。尽管有相当大的疾病负担,但阻止进展或预防发生的特定治疗是有限的。目前,缺乏全面深入探讨SAP代谢失调的研究,特别是那些强调结果变化的研究。基于核磁共振(NMR)的代谢组学结合多变量分析应用于20名SAP幸存者和30名非SAP幸存者的血清样本,以确定与不同结果相关的代谢变化。SAP幸存者和非幸存者的血清样本的判别分析显示,异亮氨酸、亮氨酸、缬氨酸、精氨酸、乳酸和3-羟基丁酸盐是非幸存者显著升高的代谢物。在Pearson相关分析中,这些鉴定出的代谢物与临床严重程度评分显示出显著的正相关。通路分析揭示了氨基酸代谢的中断,由蛋白质分解代谢驱动,以满足患者的能量需求。这项研究强调了代谢组学在揭示SAP的分子和生理机制方面的重要性。这些发现为临床医生制定针对SAP代谢途径的治疗策略提供了有价值的见解,有可能改善患者的预后。
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引用次数: 0
A detailed review of genetically encodable RFPs and far-RFPs and their applications in advanced super-resolution imaging techniques 综述了遗传可编码rfp和远编码rfp及其在先进超分辨率成像技术中的应用。
IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-15 DOI: 10.1016/j.bpc.2025.107432
Jianshu Dong , Bilal Tayyab , Jiangyun Wang
The red fluorescent proteins (RFPs) and far-red fluorescent proteins (far-RFPs) that are encoded genetically can emit fluorescence within the spectral ranges of 580–680 nm when exposed to the light of appropriate wavelengths. Unlike many RFPs derived from coral species, numerous far-RFPs are optimized synthetic constructs engineered from different orange or red-emitting progenitors. Various categories have been established for the available RFPs and far-red fluorescent proteins based on their photo-chemical profile, fluorescence mechanism, and switching kinetics. Fluorescent probes (FPs) derived from these classes are extensively utilized for labelling and visualizing in vivo and in vitro specimens. Traditional optical microscopy methods generate diffraction-limited, indistinct images owing to the restricted resolution capability of light ranging from 200 to 300 nm. Since 2005, super-resolution microscopy has been a topic of great interest due to its ability to achieve imaging at spatial resolutions of less than 100 nm. The 2014 Nobel Prize in Chemistry was awarded to Eric Betzig, Stefan Hell, and William E. Moerner for their contributions to demonstrating the effectiveness of genetically encodable fluorescent proteins in visualizing biological systems through super-resolution fluorescence microscopy. This review provides a concise overview of RFPs and far-RFPs, including the involvement of surrounding residues in chromophore intactness, stability, autocatalytic maturation and switching kinetics. All the chemical pathways proposed for photoactivation, photoconversion and photoswitching mechanisms are concisely reviewed. Subsequently, a comprehensive summary was provided regarding the various types of super-resolution techniques that are commonly employed, elucidating their underlying principles of operation, as well as the potential future applications of RFPs/far-RFPs in the field of biological imaging.
基因编码的红色荧光蛋白(rfp)和远红色荧光蛋白(far- rfp)在适当波长的光照射下可发出580-680 nm光谱范围内的荧光。与许多来自珊瑚物种的rfp不同,许多远rfp是由不同的橙色或红色发光祖细胞工程化的优化合成结构。基于它们的光化学特征、荧光机制和开关动力学,已经为可用的rfp和远红色荧光蛋白建立了各种类别。来自这些类别的荧光探针(FPs)广泛用于体内和体外标本的标记和可视化。传统的光学显微镜方法产生衍射有限,模糊的图像,由于有限的分辨率的光范围从200到300纳米。自2005年以来,超分辨率显微镜一直是一个非常感兴趣的话题,因为它能够在小于100纳米的空间分辨率下实现成像。2014年诺贝尔化学奖被授予Eric Betzig, Stefan Hell和William E. Moerner,以表彰他们通过超分辨率荧光显微镜展示遗传可编码荧光蛋白在可视化生物系统中的有效性。本文简要介绍了rfp和远rfp的研究进展,包括周围残基对发色团完整性、稳定性、自催化成熟和开关动力学的影响。简要介绍了光激活、光转化和光开关机制的所有化学途径。随后,对各种常用的超分辨率技术进行了全面的总结,阐明了其基本的工作原理,以及rfp /far- rfp在生物成像领域的潜在应用前景。
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引用次数: 0
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Biophysical chemistry
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