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Mechanism and application of immune interventions in intracerebral haemorrhage. 免疫干预在脑出血中的机制和应用。
IF 4.5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-08 DOI: 10.1017/erm.2024.22
Xiaoxiao Xu, Yuanwei Li, Shiling Chen, Xuan Wu, Jiarui Li, Gaigai Li, Zhouping Tang

Despite stroke being one of the major and increasing burdens to global health, therapeutic interventions in intracerebral haemorrhage (ICH) continue to be a challenge. Existing treatment methods, such as surgery and conservative treatment have shown limited efficacy in improving the prognosis of ICH. However, more and more studies show that exploring the specific process of immune response after ICH and taking corresponding immunotherapy may have a definite significance to improve the prognosis of cerebral haemorrhage. Therefore, immune interventions are currently under consideration as therapeutic interventions in the ICH. In this review, we aim to clarify unique immunological features of stroke, and consider the evidence for immune interventions. In acute ICH, activation of glial cells and cell death products trigger an inflammatory cascade that damages vessels and the parenchyma within minutes to hours of the haemorrhage. Immune interventions that ameliorate brain inflammation, vascular permeability and tissue oedema should be administered promptly to reduce acute immune destruction and avoid subsequent immunosuppression. A deeper understanding of the immune mechanisms involved in ICH is likely to lead to successful immune interventions.

尽管中风是全球健康的主要负担之一,而且这一负担还在不断增加,但脑出血(ICH)的治疗干预仍是一项挑战。现有的治疗方法,如手术和保守治疗,对改善 ICH 的预后效果有限。然而,越来越多的研究表明,探索 ICH 后免疫反应的特殊过程并采取相应的免疫疗法,对于改善脑出血的预后可能具有一定的意义。因此,目前正在考虑将免疫干预作为 ICH 的治疗干预手段。在本综述中,我们旨在阐明脑卒中独特的免疫学特征,并考虑免疫干预的证据。在急性 ICH 中,神经胶质细胞的激活和细胞死亡产物引发炎症级联反应,在出血后数分钟至数小时内破坏血管和实质。应及时采取能改善脑部炎症、血管通透性和组织水肿的免疫干预措施,以减少急性免疫破坏,避免后续免疫抑制。更深入地了解 ICH 所涉及的免疫机制很可能会成功地进行免疫干预。
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引用次数: 0
ATXN3: a multifunctional protein involved in the polyglutamine disease spinocerebellar ataxia type 3. ATXN3:一种与多聚谷氨酰胺病脊髓小脑共济失调 3 型有关的多功能蛋白质。
IF 4.5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-25 DOI: 10.1017/erm.2024.10
Esperanza Hernández-Carralero, Grégoire Quinet, Raimundo Freire

ATXN3 is a ubiquitin hydrolase (or deubiquitinase, DUB), product of the ATXN3 gene, ubiquitously expressed in various cell types including peripheral and neuronal tissues and involved in several cellular pathways. Importantly, the expansion of the CAG trinucleotides within the ATXN3 gene leads to an expanded polyglutamine domain in the encoded protein, which has been associated with the onset of the spinocerebellar ataxia type 3, also known as Machado-Joseph disease, the most common dominantly inherited ataxia worldwide. ATXN3 has therefore been under intensive investigation for decades. In this review, we summarize the main functions of ATXN3 in proteostasis, DNA repair and transcriptional regulation, as well as the emerging role in regulating chromatin structure. The mentioned molecular functions of ATXN3 are also reviewed in the context of the pathological expanded form of ATXN3.

ATXN3 是一种泛素水解酶(或去泛素化酶,DUB),是 ATXN3 基因的产物,在包括外周组织和神经元组织在内的各种细胞类型中普遍表达,并参与多种细胞通路。重要的是,ATXN3 基因中 CAG 三核苷酸的扩增导致编码蛋白中多谷氨酰胺结构域的扩增,这与脊髓小脑共济失调 3 型(又称马查多-约瑟夫病)的发病有关,该病是全球最常见的显性遗传共济失调。因此,几十年来,ATXN3 一直在接受深入研究。在这篇综述中,我们总结了 ATXN3 在蛋白稳态、DNA 修复和转录调控方面的主要功能,以及在调控染色质结构方面的新作用。我们还结合 ATXN3 的病理扩展形式,对上述 ATXN3 的分子功能进行了综述。
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引用次数: 0
Epigenetic tuning of tumour-associated macrophages (TAMs): a potential approach in hepatocellular carcinoma (HCC) immunotherapy. 肿瘤相关巨噬细胞(TAMs)的表观遗传学调整:肝细胞癌(HCC)免疫疗法的一种潜在方法。
IF 4.5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-25 DOI: 10.1017/erm.2024.9
Israa M Helal, Monica A Kamal, Mostafa K Abd El-Aziz, Hend M El Tayebi

Recent development in immunotherapy for cancer treatment has substantiated to be more effective than most of the other treatments. Immunity is the first line of defence of the body; nevertheless, cancerous cells can manipulate immunity compartments to play several roles in tumour progression. Tumour-associated macrophages (TAMs), one of the most dominant components in the tumour microenvironment, are recognized as anti-tumour suppressors. Unfortunately, the complete behaviour of TAMs is still unclear and understudied. TAM density is directly correlated with the progression and poor prognosis of hepatocellular carcinoma (HCC), therefore studying TAMs from different points of view passing by all the factors that may affect its existence, polarization, functions and repolarization are of great importance. Different epigenetic regulations were reported to have a direct relation with both HCC and TAMs. Here, this review discusses different epigenetic regulations that can affect TAMs in HCC whether positively or negatively.

免疫疗法在癌症治疗领域的最新发展证明,它比大多数其他疗法都更为有效。免疫是人体的第一道防线;然而,癌细胞可以操纵免疫系统,在肿瘤进展过程中发挥多种作用。肿瘤相关巨噬细胞(TAMs)是肿瘤微环境中最主要的组成部分之一,被认为是抗肿瘤抑制因子。遗憾的是,TAMs 的全部行为仍不清楚,研究也不足。TAM的密度与肝细胞癌(HCC)的进展和不良预后直接相关,因此从不同角度研究TAM,包括可能影响其存在、极化、功能和再极化的所有因素,具有重要意义。据报道,不同的表观遗传调控与 HCC 和 TAMs 都有直接关系。本综述将讨论不同的表观遗传调控对 HCC 中的 TAMs 产生的积极或消极影响。
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引用次数: 0
PARP enzymes and mono-ADP-ribosylation: advancing the connection from interferon-signalling to cancer biology. PARP酶和单ADP-核糖基化:推进从干扰素信号到癌症生物学的联系。
IF 4.5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-27 DOI: 10.1017/erm.2024.13
Barbara Morone, Giovanna Grimaldi

ADP-ribosyltransferases of the PARP family encompass a group of enzymes with variegated regulatory functions in cells, ranging from DNA damage repair to the control of cell-cycle progression and immune response. Over the years, this knowledge has led to the use of PARP1/2 inhibitors as mainstay pharmaceutical strategies for the treatment of ovarian, pancreatic, prostate and breast cancers, holding mutations in genes encoding for proteins involved in the DNA repair mechanisms (synthetic lethality). Meanwhile, the last decade has witnessed significant progress in comprehending cellular pathways regulated by mono-ADP-ribosylation, with a huge effort in the development of novel selective compounds to inhibit those PARPs endowed with mono-ADP-ribosylation activity. This review focuses on the progress achieved in the cancer field, delving into most recent findings regarding the role of a subset of enzymes - the interferon-stimulated PARPs - in cancer progression.

PARP 家族的 ADP 核糖转移酶包括一组在细胞中具有各种调节功能的酶,从 DNA 损伤修复到控制细胞周期进展和免疫反应。多年来,这些知识促使人们将 PARP1/2 抑制剂作为治疗卵巢癌、胰腺癌、前列腺癌和乳腺癌的主要药物策略,因为 DNA 修复机制(合成致死)涉及的蛋白质编码基因发生了突变。与此同时,在过去十年中,人们在理解受单 ADP 核糖基化调控的细胞通路方面取得了重大进展,并在开发新型选择性化合物以抑制具有单 ADP 核糖基化活性的 PARPs 方面做出了巨大努力。本综述将重点关注癌症领域取得的进展,深入探讨有关干扰素刺激的 PARPs 这一类酶在癌症进展中所起作用的最新发现。
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引用次数: 0
Specific and shared biological functions of PARP2 – is PARP2 really a lil’ brother of PARP1? PARP2 的特定和共享生物功能--PARP2 真的是 PARP1 的小弟弟吗?
IF 6.2 2区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-03 DOI: 10.1017/erm.2024.14
Magdolna Szántó, José Yélamos, Péter Bai
PARP2, that belongs to the family of ADP-ribosyl transferase enzymes (ART), is a discovery of the millennium, as it was identified in 1999. Although PARP2 was described initially as a DNA repair factor, it is now evident that PARP2 partakes in the regulation or execution of multiple biological processes as inflammation, carcinogenesis and cancer progression, metabolism or oxidative stress-related diseases. Hereby, we review the involvement of PARP2 in these processes with the aim of understanding which processes are specific for PARP2, but not for other members of the ART family. A better understanding of the specific functions of PARP2 in all of these biological processes is crucial for the development of new PARP-centred selective therapies.
PARP2 属于 ADP 核糖基转移酶(ART)家族,于 1999 年被发现,是一项千年发现。尽管 PARP2 最初被描述为一种 DNA 修复因子,但现在人们发现,PARP2 参与了多种生物过程的调节或执行,如炎症、致癌和癌症进展、新陈代谢或氧化应激相关疾病。在此,我们回顾了 PARP2 参与这些过程的情况,目的是了解哪些过程是 PARP2 所特有的,而 ART 家族的其他成员则没有。更好地了解 PARP2 在所有这些生物过程中的特定功能对于开发以 PARP 为中心的新型选择性疗法至关重要。
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引用次数: 0
The multifaceted functions of long non-coding RNA HOTAIR in neuropathologies and its potential as a prognostic marker and therapeutic biotarget 长非编码 RNA HOTAIR 在神经病变中的多方面功能及其作为预后标记和治疗生物靶点的潜力
IF 6.2 2区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-29 DOI: 10.1017/erm.2024.11
Faraz Ahmad, Ravi Sudesh, Atheeq Toufeeq Ahmed, Mohanapriya Arumugam, Darin Mansor Mathkor, Shafiul Haque

Long non-coding RNAs (lncRNAs) are progressively being perceived as prominent molecular agents controlling multiple aspects of neuronal (patho)physiology. Amongst these is the HOX transcript antisense intergenic RNA, often abbreviated as HOTAIR. HOTAIR epigenetically regulates its target genes via its interaction with two different chromatin-modifying agents; histone methyltransferase polycomb-repressive complex 2 and histone demethylase lysine-specific demethylase 1. Parenthetically, HOTAIR elicits trans-acting sponging function against multiple micro-RNA species. Oncological research studies have confirmed the pathogenic functions of HOTAIR in multiple cancer types, such as gliomas and proposed it as a pro-oncological lncRNA. In fact, its expression has been suggested to be a predictor of the severity/grade of gliomas, and as a prognostic biomarker. Moreover, a propound influence of HOTAIR in other aspects of brain heath and disease states is just beginning to be unravelled. The objective of this review is to recapitulate all the relevant data pertaining to the regulatory roles of HOTAIR in neuronal (patho)physiology. To this end, we discuss the pathogenic mechanisms of HOTAIR in multiple neuronal diseases, such as neurodegeneration, traumatic brain injury and neuropsychiatric disorders. Finally, we also summarize the results from the studies incriminating HOTAIR in the pathogeneses of gliomas and other brain cancers. Implications of HOTAIR serving as a suitable therapeutic target in neuropathologies are also discussed.

长非编码 RNA(lncRNA)逐渐被认为是控制神经元(病理)生理学多个方面的重要分子介质。其中包括 HOX 转录本反义基因间 RNA,通常缩写为 HOTAIR。HOTAIR 通过与两种不同的染色质修饰因子(组蛋白甲基转移酶多聚酶抑制复合体 2 和组蛋白去甲基化酶赖氨酸特异性去甲基化酶 1)相互作用,对其目标基因进行表观遗传调控。此外,HOTAIR 对多种微 RNA 具有反式作用海绵功能。肿瘤学研究证实了 HOTAIR 在神经胶质瘤等多种癌症类型中的致病功能,并提出它是一种促肿瘤的 lncRNA。事实上,它的表达被认为是胶质瘤严重程度/分级的预测因子,也是一种预后生物标志物。此外,HOTAIR 对大脑健康和疾病状态其他方面的影响也刚刚开始揭示。本综述旨在概述与 HOTAIR 在神经元(病理)生理学中的调控作用有关的所有相关数据。为此,我们讨论了 HOTAIR 在神经变性、脑外伤和神经精神疾病等多种神经元疾病中的致病机制。最后,我们还总结了将 HOTAIR 与神经胶质瘤和其他脑癌的发病机制联系起来的研究结果。此外,我们还讨论了将 HOTAIR 作为神经病理学治疗靶点的意义。
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引用次数: 0
Decoding bioactive signals of the RNA secretome: the cell-free messenger RNA catalogue 解码 RNA 分泌组的生物活性信号:无细胞信使 RNA 目录
IF 6.2 2区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-29 DOI: 10.1017/erm.2024.12
Rhys E. De Sota, Stephen R. Quake, John J. Sninsky, Shusuke Toden

Despite gene-expression profiling being one of the most common methods to evaluate molecular dysregulation in tissues, the utilization of cell-free messenger RNA (cf-mRNA) as a blood-based non-invasive biomarker analyte has been limited compared to other RNA classes. Recent advancements in low-input RNA-sequencing and normalization techniques, however, have enabled characterization as well as accurate quantification of cf-mRNAs allowing direct pathological insights. The molecular profile of the cell-free transcriptome in multiple diseases has subsequently been characterized including, prenatal diseases, neurological disorders, liver diseases and cancers suggesting this biological compartment may serve as a disease agnostic platform. With mRNAs packaged in a myriad of extracellular vesicles and particles, these signals may be used to develop clinically actionable, non-invasive disease biomarkers. Here, we summarize the recent scientific developments of extracellular mRNA, biology of extracellular mRNA carriers, clinical utility of cf-mRNA as disease biomarkers, as well as proposed functions in cell and tissue pathophysiology.

尽管基因表达谱分析是评估组织中分子失调的最常用方法之一,但与其他 RNA 类别相比,利用无细胞信使 RNA(cf-mRNA)作为基于血液的非侵入性生物标记分析物一直受到限制。然而,最近在低输入 RNA 测序和归一化技术方面取得的进展,使 cf-mRNA 的特征描述和精确定量成为可能,从而能直接揭示病理。无细胞转录组在多种疾病中的分子特征随后得到了表征,包括产前疾病、神经系统疾病、肝脏疾病和癌症,这表明这一生物区划可作为一个与疾病无关的平台。由于 mRNA 包装在无数细胞外囊泡和颗粒中,这些信号可用于开发临床可操作的非侵入性疾病生物标记物。在此,我们总结了细胞外 mRNA 的最新科学发展、细胞外 mRNA 载体的生物学特性、cf-mRNA 作为疾病生物标记物的临床用途,以及在细胞和组织病理生理学中的拟议功能。
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引用次数: 0
Roles of TRP and PIEZO receptors in autoimmune diseases. TRP 和 PIEZO 受体在自身免疫性疾病中的作用。
IF 6.2 2区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-25 DOI: 10.1017/erm.2023.23
Baoqiang Yang, D. Ma, Xue-Jun Zhu, Zewen Wu, Qingwu An, Jingwen Zhao, Xinnan Gao, Liyun Zhang
Autoimmune diseases are pathological autoimmune reactions in the body caused by various factors, which can lead to tissue damage and organ dysfunction. They can be divided into organ-specific and systemic autoimmune diseases. These diseases usually involve various body systems, including the blood, muscles, bones, joints and soft tissues. The transient receptor potential (TRP) and PIEZO receptors, which resulted in David Julius and Ardem Patapoutian winning the Nobel Prize in Physiology or Medicine in 2021, attracted people's attention. Most current studies on TRP and PIEZO receptors in autoimmune diseases have been carried out on animal model, only few clinical studies have been conducted. Therefore, this study aimed to review existing studies on TRP and PIEZO to understand the roles of these receptors in autoimmune diseases, which may help elucidate novel treatment strategies.
自身免疫性疾病是由各种因素引起的体内病理性自身免疫反应,可导致组织损伤和器官功能障碍。自身免疫性疾病可分为器官特异性自身免疫性疾病和全身性自身免疫性疾病。这些疾病通常涉及身体的各个系统,包括血液、肌肉、骨骼、关节和软组织。瞬态受体电位(TRP)和PIEZO受体,因戴维-朱利叶斯(David Julius)和阿德姆-帕塔普蒂安(Ardem Patapoutian)获得2021年诺贝尔生理学或医学奖而引起人们的关注。目前关于TRP和PIEZO受体在自身免疫性疾病中的作用的研究大多是在动物模型上进行的,只有少数临床研究。因此,本研究旨在回顾现有关于TRP和PIEZO受体的研究,以了解这些受体在自身免疫性疾病中的作用,从而有助于阐明新的治疗策略。
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引用次数: 0
Novel radiation and targeted therapy combinations for improving rectal cancer outcomes. 改善直肠癌预后的新型放射和靶向治疗组合。
IF 6.2 2区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-16 DOI: 10.1017/erm.2024.15
Kathryn Pennel, Louise Dutton, Lydia Melissourgou-Syka, Campbell S D Roxburgh, Joanna Birch, Joanne Edwards
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引用次数: 0
The Role of the Cytochrome P450 Superfamily in the Skin. 细胞色素 P450 超家族在皮肤中的作用。
IF 6.2 2区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-15 DOI: 10.1017/erm.2024.5
Qianqian Chen, Tuan Wang, Hong Pan, Xia Wu, Huipu Yuan, Jianling Mo, Yuan Wei, Ying Xiao
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引用次数: 0
期刊
Expert Reviews in Molecular Medicine
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