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Anticancer (cytotoxic, anticlonogenic, antimetastatic, immunomodulatory actions) properties of 3,5-dibromosalicylaldehyde against glioblastoma cells and DFT analyses (FT-IR, Raman, NMR, UV) as well as a molecular docking study 3,5-二溴水杨醛对胶质母细胞瘤细胞的抗癌(细胞毒性、抗克隆、抗转移、免疫调节作用)特性、DFT分析(FT-IR、拉曼、核磁共振、紫外线)以及分子对接研究
IF 2.4 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2025-02-09 DOI: 10.1111/boc.202400138
Ebru Karakaş Sarıkaya, Suray Pehlivanoğlu, Merve Özcan Türkmen, Yavuz Ekincioğlu, Feyza Kostak, Sultan Çelik, Ömer Dereli

Background Information

The primary objectives of this study were to characterize 3,5-dibromosalicylaldehyde (3,5-DBSA) and, investigate its antiproliferative, antimetastatic, cytotoxic, and immunoregulatory properties. NMR, Raman, UV, and FT-IR spectroscopies were used to characterize 3,5-DBSA. Potential conformations of 3,5-DBSA were evaluated using Spartan's MMFF method. Geometry optimization calculations using Gaussian software calculated conformation energy values.

Results

Subsequently, Raman, FT-IR, UV (ethanol) and NMR (DMSO) parameters were calculated. The experimental spectrum was compared to theoretical spectroscopic data. The present investigation investigated 3,5-DBSA's anticancer properties; therefore, docking was done once the stable structure had been identified.

Conclusion

Identifying stable structure is crucial to molecular docking studies. In order to identify the mechanism by which 3,5-DBSA binds to PI3K as a therapeutic target, molecular docking was utilized. This work is the first to show that 3,5-DBSA is cytotoxic, anticlonogenic, antimetastatic, and immunomodulatory in glioblastoma cell line U87MG compared to healthy fibroblast L929 cells. Cytotoxicity and anti-clonogenicity studies investigated 3,5-DBSA's antiproliferative activities, whereas wound healing assays assessed cell migration. The immunomodulatory effects of 3,5-DBSA in glioblastoma were assessed by measuring Netrin-1 and IL-6 protein levels. According to our findings, 3,5-DBSA may treat glioblastoma.

Significance

This work analyzes 3,5-DBSA's conformational search, characterization, molecular docking, and structural and anticancer properties.

本研究的主要目的是表征3,5-二溴水杨醛(3,5- dbsa),并研究其抗增殖、抗转移、细胞毒性和免疫调节特性。利用核磁共振、拉曼、紫外和红外光谱对3,5- dbsa进行表征。使用Spartan's MMFF方法评估3,5- dbsa的潜在构象。几何优化计算使用高斯软件计算构象能值。结果计算拉曼光谱(Raman)、红外光谱(FT-IR)、紫外(乙醇)和核磁共振(DMSO)参数。实验光谱与理论光谱数据进行了比较。本研究考察了3,5- dbsa的抗癌特性;因此,一旦确定了稳定的结构,就进行对接。结论确定稳定结构是分子对接研究的关键。为了确定3,5- dbsa作为治疗靶点与PI3K结合的机制,我们利用了分子对接。这项工作首次表明,与健康成纤维细胞L929细胞相比,3,5- dbsa在胶质母细胞瘤细胞系U87MG中具有细胞毒性、抗克隆性、抗转移性和免疫调节性。细胞毒性和抗克隆原性研究考察了3,5- dbsa的抗增殖活性,而伤口愈合试验评估了细胞迁移。通过检测Netrin-1和IL-6蛋白水平,评价3,5- dbsa对胶质母细胞瘤的免疫调节作用。根据我们的研究结果,3,5- dbsa可能治疗胶质母细胞瘤。意义本研究分析了3,5- dbsa的构象搜索、表征、分子对接、结构和抗癌特性。
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引用次数: 0
An interview with Alexis Lebecq. Winner of the French Society for Cell Biology (SBCF) thesis award 2023 亚历克西斯·勒贝克的采访。获得法国细胞生物学学会(SBCF) 2023年论文奖。
IF 2.4 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2025-02-03 DOI: 10.1111/boc.202400162
Alexis Lebecq, Paul Trevorrow
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引用次数: 0
Flotillins in membrane trafficking and physiopathology 膜转运和生理病理中的漂浮现象。
IF 2.4 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2025-01-29 DOI: 10.1111/boc.202400134
Stéphane Bodin, Hadeer Elhabashy, Ewan Macdonald, Dominic Winter, Cécile Gauthier-Rouvière

Flotillin 1 and 2 are highly conserved and homologous members of the stomatin, prohibitin, flotillin, HflK/C (SPFH) family. These ubiquitous proteins assemble into hetero-oligomers at the cytoplasmic membrane in sphingolipid-enriched domains. Flotillins play crucial roles in various cellular processes, likely by concentrating sphingosine. They primarily act as scaffolding protein complexes within membrane microdomains (also called lipid rafts) and induce endocytosis and trafficking. Their diverse cargos in the upregulated flotillin–induced trafficking (UFIT) pathway, including tyrosine kinase receptors, adhesion molecules, and neurotransmitter receptors, link them to a wide range of cellular processes and diseases. Consequently, flotillin upregulation has been associated with various pathological conditions such as cancer, metabolic disorders, and neurodegenerative diseases. Flotillins may also be co-opted by pathogens to facilitate their entry and growth within host cells.

In this review, we examined recent advancements in elucidating the structure and functions of the flotillin protein complex, including its implications in favoring the generation of sphingosine 1-phosphate, an essential bioactive lipid. We emphasized how the recent cryo-electron microscopy (cryo-EM) structure of a truncated cone-shaped cage composed of 22 copies of flotillin 1 and 2 subunits has enhanced our understanding of the flotillin complex organization within membrane microdomains and its role in membrane remodeling. We also explored how flotillin upregulation can perturb endosomal trafficking and contribute to various pathologies.

A comprehensive understanding of flotillin oligomer organization and function is crucial to developing targeted therapies for diseases associated with flotillin overexpression.

Flotillin 1和2是stomatin, prohibitin, Flotillin, HflK/C (SPFH)家族中高度保守的同源成员。这些无处不在的蛋白质在鞘脂富集区域的细胞质膜上组装成异聚物。Flotillins在各种细胞过程中发挥着至关重要的作用,可能是通过集中鞘氨醇。它们主要作为膜微域(也称为脂筏)内的支架蛋白复合物并诱导内吞和运输。它们在上调的flotilin诱导运输(UFIT)途径中的不同货物,包括酪氨酸激酶受体、粘附分子和神经递质受体,将它们与广泛的细胞过程和疾病联系起来。因此,flotilin的上调与各种病理状况,如癌症、代谢紊乱和神经退行性疾病有关。漂浮物也可能被病原体吸收,以促进它们在宿主细胞内的进入和生长。在这篇综述中,我们研究了最近在阐明flotillin蛋白复合物的结构和功能方面的进展,包括它在促进生成鞘氨醇1-磷酸(一种必需的生物活性脂质)方面的意义。我们强调了最近由22个flotillin 1和2亚基拷贝组成的截锥形笼的冷冻电镜(cro - em)结构如何增强了我们对膜微域内flotillin复合物组织及其在膜重塑中的作用的理解。我们还探讨了flotilin上调如何扰乱内体运输并导致各种病理。全面了解flotillin寡聚物的组织和功能对于开发与flotillin过表达相关疾病的靶向治疗至关重要。
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引用次数: 0
Revealing mitochondrial architecture and functions with single molecule localization microscopy 用单分子定位显微镜揭示线粒体结构和功能。
IF 2.4 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2025-01-29 DOI: 10.1111/boc.202400082
Nicolas Jolivet, Giulia Bertolin

Understanding the spatiotemporal organization of components within living systems requires the highest resolution possible. Microscopy approaches that allow for a resolution below 250 nm include electron and super-resolution microscopy (SRM). The latter combines advanced imaging techniques and the optimization of image processing methods. Over the last two decades, various SRM-related approaches have been introduced, especially those relying on single molecule localization microscopy (SMLM). To develop and apply SMLM approaches, mitochondria are an ideal cellular compartment due to their size, which is below the standard diffraction limit. Furthermore, mitochondria are a dynamic yet narrow compartment, and a resolution below 250 nm is required to study their composition and multifaceted functions. To this end, several SMLM technologies have been used to reveal mitochondrial composition. However, there is still room for improvement in existing techniques to study protein–protein interactions and protein dynamics within this compartment. This review aims to offer an updated overview of the existing SMLM techniques and probes associated with mitochondria to enhance their resolution at the nanoscale. Last, it paves the way for future SMLM improvements to better resolve mitochondrial dynamics and functions.

理解生命系统中组成部分的时空组织需要尽可能高的分辨率。分辨率低于250纳米的显微镜方法包括电子和超分辨率显微镜(SRM)。后者结合了先进的成像技术和优化的图像处理方法。在过去的二十年中,各种与srm相关的方法已经被引入,特别是那些依赖于单分子定位显微镜(SMLM)的方法。为了开发和应用SMLM方法,线粒体是理想的细胞隔室,因为它们的大小低于标准衍射极限。此外,线粒体是一个动态但狭窄的隔间,需要250 nm以下的分辨率来研究它们的组成和多方面的功能。为此,已经使用了几种SMLM技术来揭示线粒体组成。然而,在现有的技术中,研究蛋白质-蛋白质相互作用和蛋白质动力学在这个隔室中仍然有改进的空间。本综述旨在提供与线粒体相关的现有SMLM技术和探针的最新概述,以提高其在纳米尺度上的分辨率。最后,它为未来的SMLM改进铺平了道路,以更好地解决线粒体动力学和功能。
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引用次数: 0
Organoid Ethical Typology: varieties of three-dimensional stem cell constructs and the many issues they raise in bioethics 类器官伦理类型学:三维干细胞结构的多样性及其在生物伦理学中提出的许多问题。
IF 2.4 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2025-01-24 DOI: 10.1111/boc.202400093
Maxence Gaillard, Charles H. Pence, Mylène Botbol-Baum

The advancement of and prospects for stem cell research raise a number of specific ethical issues. While navigating the ethical landscape of stem cell research is often challenging for biology researchers and biotechnology innovators, it is also difficult for the public and other persons of concern (from ethicists to policy-makers) to grasp the technicalities of a burgeoning field that develops in many directions. Organoids are one of these new biotechnological constructs that are currently eliciting a rich debate in bioethics. In this guide, we argue that different types of organoids have different emerging properties with different ethical implications. Going from general properties to particular ones, we propose a typology of organoid technology and other associated biotechnology from a philosophical and ethical perspective. We point to relevant ethical issues and try to convey the sense of uncertainty peculiar to ongoing research and emerging technological objects.

干细胞研究的进展和前景提出了一些具体的伦理问题。干细胞研究的伦理问题对生物学研究者和生物技术创新者来说是一个挑战,公众和其他相关人士(从伦理学家到政策制定者)也很难掌握这个新兴领域的技术细节。类器官是这些新的生物技术结构之一,目前在生物伦理学中引起了广泛的争论。在本指南中,我们认为不同类型的类器官具有不同的新兴特性,具有不同的伦理含义。从一般性质到特殊性质,我们从哲学和伦理的角度提出了类器官技术和其他相关生物技术的类型学。我们指出了相关的伦理问题,并试图传达正在进行的研究和新兴技术对象特有的不确定性。
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引用次数: 0
Neutral lipids restrict the mobility of broken DNA molecules during comet assays 中性脂质在彗星分析中限制了断裂DNA分子的流动性。
IF 2.4 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2025-01-24 DOI: 10.1111/boc.202400141
Caroline Soulet, Jordi Josa-Castro, María Moriel-Carretero

One widespread technique to assess in relative terms the amount of broken DNA present in the genome of individual cells consists of immobilizing the cell's nucleus under an agarose pad (called the nucleoid) and subjecting the whole genome to electrophoresis to force broken DNA molecules out of it. Since the migrating broken DNA molecules create a tail behind the nucleoid, this technique is named the comet assay. While performing comet assays regularly, we systematically observed circular regions devoid of DNA within the nucleoid region. We characterize here that these correspond to clusters of neutral (apolar) lipids, since they could be labeled with neutral lipid-dying molecules, increased when cells were fed with oleic acid, and were irresponsive to the electrophoretic field. Of relevance, de-lipidation assays, either in vivo, or in vitro using acetone, show that these neutral lipids (NL) within the nucleoid limit the ability of broken DNA molecules to migrate into the comet tail. From a technical point of view, we show that de-lipidation permits a wider range for the detection of broken DNA molecules. Biologically, we put forward the notion that NL in contact with DNA may locally exert regulatory functions within the cell's nucleus.

一种广泛应用的评估单个细胞基因组中断裂DNA相对数量的技术包括将细胞核固定在琼脂糖垫(称为类核)下,并对整个基因组进行电泳以迫使断裂的DNA分子脱离。由于迁移的断裂DNA分子在类核后面形成一条尾巴,这项技术被命名为彗星试验。在定期进行彗星分析时,我们系统地观察到在类核区域内缺乏DNA的圆形区域。我们在这里描述了这些与中性(极性)脂质簇相对应的特征,因为它们可以被中性脂质死亡分子标记,当细胞被喂以油酸时增加,并且对电泳场无反应。与此相关的是,在体内或体外使用丙酮进行的去脂化试验表明,类核内的中性脂质(NL)限制了断裂DNA分子迁移到彗星尾部的能力。从技术的角度来看,我们表明,去脂化允许更广泛的范围内检测破碎的DNA分子。在生物学上,我们提出了与DNA接触的NL可能在细胞核内局部发挥调节功能的概念。
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引用次数: 0
The crosstalk between exosomal miRNA and ferroptosis: A narrative review 外泌体miRNA与铁下垂之间的串扰:一个叙述性的回顾。
IF 2.4 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2025-01-24 DOI: 10.1111/boc.202400077
Zahra Nashtahosseini, Masoumeh Nejatollahi, Ahmad Fazilat, Elahe Zarif Fakoor, Alireza Emamvirdizadeh, Kamran Bahadori, Niloofar Sadat Hadian, Mohammad Valilo

Ferroptosis is a type of cell death that multiple mechanisms and pathways contribute to the positive and negative regulation of it. For example, increased levels of reactive oxygen species (ROS) induce ferroptosis. ferroptosis unlike apoptosis, it is not dependent on caspases, but is dependent on iron. Exosomes are membrane-bound vesicles with a size of about 30 to 150 nm, contain various cellular components, including DNA, RNA, microRNAs (miRNAs), lipids, and proteins, which are genetically similar to their cells of origin. Exosomes are found in all bodily fluids, including blood, saliva, and urine. Cells often release exosomes after their fusion with the cell membrane. They play an important role in immune regulation and cell-cell communication. miRNAs, which are noncoding RNAs with a length of about 18 to 24 nucleotides, are involved in regulating gene expression after transcription. Emerging data suggests that exosomal miRNAs are implicated in various pathophysiological mechanisms of cells, including metastasis, drug resistance, and cell death. In addition, functional studies have indicated that exosomal miRNAs can play a key role in the modulation of cell death by regulating ferroptosis. Therefore, in this review, given the importance of exosomal miRNAs in ferroptosis, we decided to elucidate the relationship between exosomal miRNAs and ferroptosis in various diseases.

铁下垂是一种多种机制和途径共同调控的细胞死亡。例如,活性氧(ROS)水平的增加会导致铁下垂。与细胞凋亡不同,铁下垂不依赖于半胱天冬酶,而是依赖于铁。外泌体是膜结合的囊泡,大小约为30 ~ 150nm,含有各种细胞成分,包括DNA、RNA、microrna (miRNAs)、脂质和蛋白质,它们与其起源细胞具有遗传相似性。外泌体存在于所有体液中,包括血液、唾液和尿液。细胞通常在与细胞膜融合后释放外泌体。它们在免疫调节和细胞间通讯中发挥重要作用。mirna是长度约为18 ~ 24个核苷酸的非编码rna,在转录后参与调控基因表达。新出现的数据表明,外泌体mirna与细胞的各种病理生理机制有关,包括转移、耐药和细胞死亡。此外,功能研究表明,外泌体mirna可以通过调节铁下垂在细胞死亡的调节中发挥关键作用。因此,在这篇综述中,考虑到外泌体miRNAs在铁下垂中的重要性,我们决定阐明外泌体miRNAs与各种疾病铁下垂之间的关系。
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引用次数: 0
Metabolism-lipid droplet-nucleic acid crosstalk to regulate lipid storage and other cellular processes in oleaginous Rhodococcus bacteria 代谢-脂滴-核酸串扰调节产油红球菌的脂质储存和其他细胞过程。
IF 2.4 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2025-01-24 DOI: 10.1111/boc.202400094
Héctor M. Alvarez, Mariana P. Lanfranconi, Martín A. Hernández

Actinobacteria belonging to Mycobacterium and Rhodococcus genera are able to synthesize and intracellularly accumulate variable amounts of triacylglycerols (TAG) in the form of lipid droplets (LDs). The lipid storage capacity of LDs in cells is controlled by the balance between lipogenesis and lipolysis. The growth of LDs in bacterial cells may be directly promoted by TAG biosynthesis, whereas TAG degradation might result in the reduction of LD sizes and lipid storage capacity. Therefore, LD formation and turnover have to be precisely regulated to maintain a balanced lipid distribution, coupling gene regulation with the metabolic state of the cell. In eukaryotic cells, LDs have emerged as critical mediators of diverse cellular responses, including fatty acid trafficking and modulation of transcriptional programs. Recent studies performed in mycobacteria and rhodococci suggested the existence of similar crosstalk mechanisms between lipid metabolism, LDs, and gene expression regulation in cells. This review connects and organizes results of different studies in a comprehensive framework for providing evidence of “lipid metabolism-LDs-genomic DNA” crosstalk occurring in TAG-accumulating actinobacteria. We provide examples indicating that bacterial cells evolved sensing mechanisms that detect lipid metabolites changes as indicators of metabolic states, and adapt their transcriptional profiles through epigenetic-like mechanisms mediated by LD-associated proteins. Here, we describe the molecular interconnections of this coupling system and the main role of each component that integrates the information about the cellular metabolic state into the regulation of lipogenesis, LD formation and transcription in oleaginous bacteria.

属于分枝杆菌属和红球菌属的放线菌能够合成并在细胞内以脂滴(ld)的形式积累可变量的三酰基甘油(TAG)。脂肪在细胞中的储存能力是由脂肪生成和脂肪分解之间的平衡控制的。TAG的生物合成可能直接促进细菌细胞内LD的生长,而TAG的降解可能导致LD大小和脂质储存能力的降低。因此,必须精确调节LD的形成和转化,以维持平衡的脂质分布,将基因调控与细胞代谢状态相结合。在真核细胞中,ld已成为多种细胞反应的关键介质,包括脂肪酸运输和转录程序的调节。最近在分枝杆菌和红球菌中进行的研究表明,细胞中脂质代谢、ld和基因表达调控之间存在类似的串音机制。这篇综述将不同的研究结果整合在一个综合的框架中,以提供在tag积累的放线菌中发生“脂质代谢- lds -基因组DNA”串音的证据。我们提供的例子表明,细菌细胞进化出了检测脂质代谢物变化的传感机制,作为代谢状态的指标,并通过由ld相关蛋白介导的表观遗传样机制调整其转录谱。在这里,我们描述了这个耦合系统的分子相互联系,以及每个组成部分的主要作用,这些组成部分将细胞代谢状态的信息整合到产油细菌的脂肪生成、LD形成和转录的调节中。
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引用次数: 0
An interview with Meryem Baghdadi, winner of The French Society for Cell Biology (SBCF) Young Researcher Prize 2024 这是对法国细胞生物学学会(SBCF) 2024年青年研究员奖得主Meryem Baghdadi的采访。
IF 2.4 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2025-01-09 DOI: 10.1111/boc.202400159
Meryem B. Baghdadi, Paul Trevorrow
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引用次数: 0
Phosphoinositide signaling in the nucleus: Impacts on chromatin and transcription regulation 核内磷酸肌肽信号传导:对染色质和转录调控的影响。
IF 2.4 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2024-12-20 DOI: 10.1111/boc.202400096
Nesrine Hifdi, Mathilde Vaucourt, Karim Hnia, Ganna Panasyuk, Marie Vandromme

Phosphoinositides also called Polyphosphoinositides (PPIns) are small lipid messengers with established key roles in organelle trafficking and cell signaling in response to physiological and environmental inputs. Besides their well-described functions in the cytoplasm, accumulating evidences pointed to PPIns involvement in transcription and chromatin regulation. Through the description of previous and recent advances of PPIns implication in transcription, this review highlights key discoveries on how PPIns modulate nuclear factors activity and might impact chromatin to modify gene expression. Finally, we discuss how PPIns nuclear and cytosolic metabolisms work jointly in orchestrating key transduction cascades that end in the nucleus to modulate gene expression.

磷酸肌苷也被称为多磷酸肌苷(PPIns),是一种小的脂质信使,在响应生理和环境输入的细胞器运输和细胞信号传导中起着关键作用。除了在细胞质中的功能,越来越多的证据表明PPIns参与转录和染色质调节。本文通过对PPIns在转录中的作用的既往和近期进展的描述,重点介绍了PPIns如何调节核因子活性并可能影响染色质以修饰基因表达的关键发现。最后,我们讨论了PPIns的核代谢和胞质代谢如何共同协调关键的转导级联,最终在细胞核中调节基因表达。
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引用次数: 0
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