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Self-organisation of early stress response in the biology of cancer 癌症生物学中早期应激反应的自我组织
Pub Date : 2024-03-18 DOI: 10.18388/pb.2021_521
J. Erenpreisa, K. Salmina, N. Vainshelbaum, I. Inashkina, T. Freivalds
The early stress response by AP-1 (FOS/JUN), supported by upregulation of c-Myc and involved in cell-fate changes and adaptation to hostile environments, is increased in cancer. The review shows the biphasic character of this response with negative feed-back typically lasting a few hours as a feature of the genome regulation by self-organising criticality. It involves  rapid splitting of the pericentromeric heterochromatin clusters, opening of the active chromatin, and a massive transcription acceleration wave. Phylostratigraphic analysis revealed that AP-1 genes evolved in the Cambrian explosion ~500 Mya integrating the protein interaction networks of reproduction including proto-placenta intertwined with cytokine and immunity pathways, sex determination, oocyte maturation, and embryonal stemness. The peak  of this response as part of accelerated cell senescence led by AP-1 and IL-1β was found in breast cancer cell-line resistant to doxorubicin. Adaptability of aggressive cancer to treatments can be explained by emergent stress response evolutionarily protecting reproduction
在癌症中,AP-1(FOS/JUN)的早期应激反应得到了 c-Myc 上调的支持,并参与了细胞命运的改变和对恶劣环境的适应。综述显示了这种反应的双相特性,其负反馈通常持续几个小时,这是基因组自组织临界调控的一个特征。它包括中心粒周围异染色质群的快速分裂、活性染色质的开放以及大规模的转录加速波。植物地层学分析显示,AP-1 基因是在约 500 Mya 的寒武纪大爆发中进化而来的,它整合了生殖的蛋白质相互作用网络,包括与细胞因子和免疫途径、性别决定、卵母细胞成熟和胚胎干性交织在一起的原胎盘。在对多柔比星耐药的乳腺癌细胞系中发现,这种反应的峰值是由 AP-1 和 IL-1β 导致的细胞加速衰老的一部分。侵袭性癌症对治疗的适应性可以用进化过程中出现的保护生殖的应激反应来解释
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引用次数: 0
Profesor Jakub Karol Parnas: 140 rocznica urodzin 雅各布-卡罗尔-帕尔纳斯教授诞辰 140 周年
Pub Date : 2024-03-12 DOI: 10.18388/pb.2021_524
J. Barańska, A. Dżugaj, A. Szewczyk
In 2024, it will be 140 years since the birth of Jan Karol Parnas, one of the most outstanding biochemists and one of the most outstanding Polish scientists of the first half of the 20th century. The article presents a synthetic biography of Prof. Parnas, his influence on the organization of scientific life in interwar Poland, and presents his students and collaborators who created the so-called "The School of Parnassus". It shows how this figure still influences the thinking of Polish biochemists about their Society and the attitude towards biochemical communities abroad, especially in Ukraine, which owes as much to Prof. Parnas as Poland does.
2024 年,20 世纪上半叶最杰出的生物化学家和波兰最杰出的科学家之一扬-卡罗尔-帕尔纳斯(Jan Karol Parnas)将诞辰 140 周年。文章介绍了帕尔纳斯教授的综合传记、他对战时波兰科学生活组织的影响,并介绍了他的学生和合作者,他们创建了所谓的 "帕尔纳斯学派"。文章展示了这位人物如何仍然影响着波兰生物化学家对其学会的思考,以及对国外生物化学家的态度,尤其是在乌克兰,乌克兰和波兰一样都要感谢帕尔纳斯教授。
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引用次数: 0
MicroRNA-mediated gene regulation and the resilience of multicellular animals 微RNA介导的基因调控与多细胞动物的恢复能力
Pub Date : 2024-02-28 DOI: 10.18388/pb.2021_515
Victor Ambros
MicroRNAs are small RNAs that enable parts of the genome to regulate the other parts of the genome by RNA::RNA complementarity. Genes that encode microRNAs function as trans-acting regulators of hundreds of other genes, primarily by inhibiting the production of protein from mRNAs to which the microRNAs can bind by base pairing. MicroRNAs and their Argonaute partner proteins constitute a regulatory complex (the miRISC) that exhibits astonishing regulatory versatility. microRNAs have been shown to perform diverse roles in genetic regulatory networks (GRNs) – to control developmental switches, to dampen gene expression noise, to coordinate multigene functional modules, and more broadly, to confer robustness and resilience to developmental and homeostatic processes. Genetic analysis reveals that the function of particular microRNAs can be conditional, such that the microRNA is required under particular environmental or physiological conditions, but relatively dispensable under other conditions. The diversity and versatility of microRNA function in animal systems reflects the many ways that miRISC can be regulated by cellular signaling pathways, and the structure-function interplay among microRNA, target, and Argonaute. 
微小RNA是一种小型RNA,通过RNA::RNA互补,使基因组的一部分能够调节基因组的其他部分。编码 microRNAs 的基因是数百个其他基因的反式调节因子,主要通过碱基配对抑制与 microRNAs 结合的 mRNAs 产生蛋白质。microRNAs 及其 Argonaute 伙伴蛋白构成了一个调控复合体(miRISC),表现出惊人的调控多功能性。microRNAs 已被证明在遗传调控网络(GRNs)中发挥多种作用--控制发育开关、抑制基因表达噪音、协调多基因功能模块,以及更广泛地赋予发育和平衡过程以稳健性和复原力。遗传分析表明,特定 microRNA 的功能可能是有条件的,例如在特定环境或生理条件下需要这种 microRNA,但在其他条件下则相对可有可无。动物系统中 microRNA 功能的多样性和多功能性反映了细胞信号通路调节 miRISC 的多种方式,以及 microRNA、靶标和 Argonaute 之间的结构-功能相互作用。
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引用次数: 0
The p53 protein – not only the guardian of the genome p53 蛋白--不仅是基因组的守护者
Pub Date : 2024-02-28 DOI: 10.18388/pb.2021_518
M. Rusin
The p53 tumor suppressor protein is best known as an activator of cell cycle arrest and apoptosis. Only a fraction of p53-activated genes encode proteins affecting cellular replication and various forms of cell death (apoptosis, ferroptosis, autophagy). The p53-regulated genes can be divided into so-called the core transcriptional program, which comprises genes activated in most cell types by most activators, and into the group of genes activated in in cell- or stress-specific manner. Activation of p53 occurs via the extensive set of posttranslational modifications, which adjust its stability, interaction with other transcription regulators, and its ability to form a tetramer. Surprisingly, in mouse models, the activation of the best-studied p53 target genes encoding the inhibitor of the cell cycle (CDKN1A) or the inducers of apoptosis (e.g. NOXA, PUMA) is dispensable for protection against cancers. Thus, the non-classical functions of p53 must be studied to better understand its tumor suppressive mechanisms.
p53 抑癌基因是细胞周期停滞和细胞凋亡的激活因子。只有一小部分 p53 激活的基因编码的蛋白质会影响细胞复制和各种形式的细胞死亡(凋亡、铁变性、自噬)。p53 调节的基因可分为所谓的核心转录程序(包括在大多数细胞类型中被大多数激活剂激活的基因)和以细胞或应激特异性方式激活的基因组。p53 的激活是通过一系列广泛的翻译后修饰进行的,这些修饰调整了其稳定性、与其他转录调节因子的相互作用以及形成四聚体的能力。令人惊讶的是,在小鼠模型中,研究最充分的 p53 靶基因编码细胞周期抑制剂(CDKN1A)或细胞凋亡诱导剂(如 NOXA、PUMA)的活化对于防止癌症的发生是必不可少的。因此,必须研究 p53 的非经典功能,以更好地了解其抑制肿瘤的机制。
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引用次数: 0
Gliwice Scientific Meetings as a forum for discussion of research projects.Personal impressions 格利维采科学会议作为讨论研究项目的论坛。
Pub Date : 2024-02-21 DOI: 10.18388/pb.2021_516
Krzysztof Szyfter
The article has been written for the occasion of 25 Anniversary of Gliwice Scientific Meetings (GSN). For this reason, I am going to present scientific contacts of the Institute of Oncology at Gliwice with the Institute of Human Genetics of the Polish Academy of Sciences at Poznań not only at conference occasions but also in regular research manner.
这篇文章是为纪念格利维采科学会议(GSN)25 周年而写的。为此,我将介绍格利维采肿瘤研究所与位于波兹南的波兰科学院人类遗传学研究所之间的科学联系,不仅在会议场合,而且在常规研究中。
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引用次数: 0
Epidermal factor Foxn1 as a regulator of antioxidant defense in the skin 表皮因子 Foxn1 是皮肤抗氧化防御的调节因子
Pub Date : 2024-01-30 DOI: 10.18388/pb.2021_503
Sylwia Machcińska-Zielińska, Barbara Gawrońska-Kozak
The skin, as the largest organ of the body, is constantly exposed to environmental threats, including: injuries and oxidative stress. The thioredoxin system is one of the skin antioxidant systems , which protects cells against oxidative stress, regulates cell migration, proliferation and apoptosis, and also participates in signal transmission by regulating the activity of transcription factors. Recent studies have shown a correlation between the epidermal transcription factor Foxn1 and the thioredoxin system in mouse skin. Mass spectrometry analysis, followed by in vitro and in vivo experiments, showed that Foxn1 in keratinocytes regulates elements of the electron transport chain as well as the thioredoxin system (Txn2, Txnrd3), especially under hypoxic condition. High levels of Txnrd3 mRNA were detected for the first time in the injured skin of Foxn1+/+ mice compared to Foxn1-/- mice, and also showed that Foxn1 in keratinocytes upregulates Txnrd3 protein expression. Moreover, in silico analyzes indicated possible binding sites of the transcription factor Foxn1 in the Txn system. In conclusion, the data presented in this review identify Foxn1 as a novel component of the skin antioxidant system.
皮肤作为人体最大的器官,经常暴露在环境威胁之下,包括受伤和氧化应激。硫氧还蛋白系统是皮肤抗氧化系统之一,它能保护细胞免受氧化应激,调节细胞迁移、增殖和凋亡,还能通过调节转录因子的活性参与信号传递。最近的研究表明,小鼠皮肤中的表皮转录因子 Foxn1 与硫氧还蛋白系统之间存在相关性。质谱分析以及体外和体内实验表明,角质形成细胞中的 Foxn1 可调节电子传递链元素以及硫代毒素系统(Txn2、Txnrd3),尤其是在缺氧条件下。与 Foxn1-/- 小鼠相比,在 Foxn1+/+ 小鼠受伤的皮肤中首次检测到了高水平的 Txnrd3 mRNA,同时还表明角质形成细胞中的 Foxn1 能上调 Txnrd3 蛋白的表达。此外,硅学分析表明了转录因子 Foxn1 在 Txn 系统中可能的结合位点。总之,本综述提供的数据表明,Foxn1 是皮肤抗氧化系统的一个新的组成部分。
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引用次数: 0
Evaluation of the regeneration process of the sciatic nerve of a mouse animal model after application of freezing, crushing or electrocoagulation damage 评估小鼠动物模型坐骨神经在受到冷冻、挤压或电凝损伤后的再生过程
Pub Date : 2024-01-30 DOI: 10.18388/pb.2021_504
Dariusz Górka, Krzysztof Suszyński, Natalia Białoń, Mikołaj Górka, Michał Trzęsicki, Kacper Zając, A. Dolińska, Filip Tomsia
The problem of regeneration of damaged peripheral nerves is an ongoing topic and has long been the subject of intensive research worldwide. This study examined the morphological and functional evaluation of the regeneration process within the damaged sciatic nerve, a mouse animal model. The effect of impaired expression of the TSC-1 gene on the process of nerve regeneration was evaluated, depending on the mode of damage. The research object consisted of 48, 2-month-old male TSC lines. The test group consisted of animals that underwent damage to the sciatic nerve by crushing, freezing and electrocoagulation, while the control group includes mice whose sciatic nerve was not damaged. Behavioral tests were conducted to evaluate the functional return of the limb, after 3,5,7 and 14 days. The first changes in the regeneration process of the damaged neurite are observed as early as day 3 after the injury, while on day 14 after the injury the functional return of the damaged limb was noted.
受损周围神经的再生问题是一个持续的话题,长期以来一直是全世界深入研究的主题。本研究考察了受损坐骨神经(小鼠动物模型)再生过程的形态和功能评估。根据损伤模式,评估了 TSC-1 基因表达受损对神经再生过程的影响。研究对象包括 48 只 2 个月大的雄性 TSC 系小鼠。试验组包括坐骨神经受到挤压、冷冻和电凝损伤的动物,对照组包括坐骨神经未受损的小鼠。分别在 3、5、7 和 14 天后进行行为测试,以评估肢体功能的恢复情况。早在损伤后第 3 天,就能观察到受损神经元再生过程的最初变化,而在损伤后第 14 天,就能注意到受损肢体的功能恢复。
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引用次数: 0
Conference report 6th National Conference "BIOTECHNOLOGY HAS MANY NAMES" 会议报告 第六届 "生物技术有多种名称 "全国会议
Pub Date : 2024-01-24 DOI: 10.18388/pb.2021_511
Michał Rurek, Joanna Perła-Kaján, Karolina Pusiak
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引用次数: 0
Epigenetics and the improvement of crop plants 表观遗传学与作物改良
Pub Date : 2024-01-15 DOI: 10.18388/pb.2021_514
Klaudia Bernacka, M. Achrem, A. Kalinka
Epigenetics is a term that refers to the changes in gene expression that are heritable and induced by DNA methylation, histones post-translational modifications, or sncRNA, not resulting from the DNA sequence rearrangements. Epigenetic modifications influence gene expression, and thus, the plasticity of plants' development and phenotype in response to external and internal factors. Until recently, the only known epigenetic modification of the DNA in eukaryotic organisms was 5-methylcytosine. The growing interest in epigenetics and the development of sensitive detection methods enabled the discovery of other modifications of the DNA nitrogenous bases, i.e., 4-methylcytosine and 6-methyladenine. However, whilst research on the 5mC distribution and role in eukaryotic organisms is widespread, analyses regarding 6mA are scarced. Nevertheless, there are indications of a potential epigenetic role of 6-methyladenine in eukaryotic genomes. Understanding epigenetic mechanisms, which are triggered in response to environmental changes, is crucial for agriculture. This review shows epigenetic mechanisms, with particular emphasis on adenine methylation in plants, as well as the role of epigenetic variation in epibreeding, affecting the improvement of agronomic traits.
表观遗传学(Epigenetics)是一个术语,指基因表达的变化是可遗传的,是由 DNA 甲基化、组蛋白翻译后修饰或 sncRNA 诱导的,而不是由 DNA 序列重排引起的。表观遗传修饰影响基因表达,进而影响植物发育和表型对内外因素的可塑性。直到最近,真核生物中唯一已知的 DNA 表观遗传修饰是 5-甲基胞嘧啶。随着人们对表观遗传学的兴趣日益浓厚以及灵敏检测方法的发展,人们发现了 DNA 含氮碱基的其他修饰,即 4-甲基胞嘧啶和 6-甲基腺嘌呤。然而,尽管有关 5mC 在真核生物体内的分布和作用的研究非常广泛,但有关 6mA 的分析却很少。不过,有迹象表明 6-甲基腺嘌呤在真核生物基因组中具有潜在的表观遗传作用。了解随环境变化而触发的表观遗传机制对农业至关重要。本综述介绍了表观遗传机制,特别强调了植物中的腺嘌呤甲基化,以及表观遗传变异在表观育种中的作用,它影响着农艺性状的改良。
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引用次数: 0
The role of physicochemical processes in the formation of the 3D genome and compartmentalization of the cell nucleus 物理化学过程在形成三维基因组和细胞核分区中的作用
Pub Date : 2024-01-15 DOI: 10.18388/pb.2021_512
Sergey V. Razin
The review analyzes the role of physicochemical processes in the formation of the function-dependent architecture of the cell nucleus, built on the platform of a folded genome. The main attention is paid to various forms of the phase separation process, primarily the processes of liquid-liquid phase separation and polymer-polymer phase separation. The role of these processes in the formation of chromatin compartments and maintenance of three-dimensional genome architecture is discussed in detail. The relationship between genome activity and the creation of functional compartments in the cell nucleus is also analyzed.
这篇综述分析了物理化学过程在建立在折叠基因组平台上的细胞核功能相关结构形成过程中的作用。主要关注各种形式的相分离过程,主要是液-液相分离过程和聚合物-聚合物相分离过程。详细讨论了这些过程在染色质区室的形成和三维基因组结构的维持中的作用。此外,还分析了基因组活动与细胞核中功能区的形成之间的关系。
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引用次数: 0
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Postępy Biochemii
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