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Preclinical activities of Cassia tora Linn against aging-related diseases. 决明子抗衰老相关疾病的临床前研究。
IF 6.2 2区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-10-25 DOI: 10.1017/erm.2022.33
Sun-Young Hwang, Chang-Su Na, Byeong Cheol Moon, Jung-Hyun Shim, Mee-Hyun Lee

Globally, an aging population is increasing, and aging is a natural physiological process and a major risk factor for all age-related diseases. It seriously threatens personal health and imposes a great economic burden. Therefore, there is a growing scientific interest in strategies for well-aging with prevention and treatment of age-related diseases. The seed, root, stem or leaves of Cassia tora Linn. are useful for anti-bacteria, anti-hyperlipidemia and anti-obesity due to its pharmacological activities such as anti-inflammation and anti-oxidant both in vitro and in vivo. Nevertheless, no clinical trials have been attempted so far, therefore here we would like to understand the current preclinical activities for aging-related disease models including cataract, metabolic dysfunction and neurodegeneration, then discuss their preparation for clinical trials and perspectives.

在全球范围内,人口老龄化日益加剧,老龄化是一种自然的生理过程,也是所有与年龄有关的疾病的主要危险因素。它严重威胁个人健康,并造成巨大的经济负担。因此,越来越多的科学兴趣是如何预防和治疗与年龄有关的疾病。决明子决明子的种子、根、茎或叶在体内体外均具有抗炎、抗氧化等药理作用,具有抗菌、抗高脂血症、抗肥胖等作用。然而,到目前为止,还没有临床试验的尝试,因此,我们想了解目前的衰老相关疾病模型的临床前活动,包括白内障,代谢功能障碍和神经退行性变,然后讨论他们的临床试验准备和观点。
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引用次数: 0
Metabolic signatures of immune cells in chronic kidney disease. 慢性肾脏疾病免疫细胞的代谢特征。
IF 6.2 2区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-10-21 DOI: 10.1017/erm.2022.35
Jie Li, Yi Yang, Yanan Wang, Qing Li, Fan He

Immune cells play a key role in maintaining renal dynamic balance and dealing with renal injury. The physiological and pathological functions of immune cells are intricately connected to their metabolic characteristics. However, immunometabolism in chronic kidney disease (CKD) is not fully understood. Pathophysiologically, disruption of kidney immune cells homeostasis causes inflammation and tissue damage via triggering metabolic reprogramming. The diverse metabolic characteristics of immune cells at different stages of CKD are strongly associated with their different pathological effect. In this work, we reviewed the metabolic characteristics of immune cells (macrophages, natural killer cells, T cells, natural killer T cells and B cells) and several non-immune cells, as well as potential treatments targeting immunometabolism in CKD. We attempt to elaborate on the metabolic signatures of immune cells and their intimate correlation with non-immune cells in CKD.

免疫细胞在维持肾脏动态平衡和处理肾损伤中起着关键作用。免疫细胞的生理和病理功能与其代谢特性有着错综复杂的联系。然而,慢性肾脏疾病(CKD)的免疫代谢尚不完全清楚。病理生理上,肾脏免疫细胞稳态的破坏通过触发代谢重编程引起炎症和组织损伤。CKD不同阶段免疫细胞不同的代谢特性与其不同的病理作用密切相关。在这项工作中,我们综述了免疫细胞(巨噬细胞、自然杀伤细胞、T细胞、自然杀伤T细胞和B细胞)和几种非免疫细胞的代谢特征,以及针对CKD免疫代谢的潜在治疗方法。我们试图阐述CKD中免疫细胞的代谢特征及其与非免疫细胞的密切关系。
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引用次数: 6
Extracellular vesicle isolation, purification and evaluation in cancer diagnosis. 细胞外囊泡的分离纯化及其在肿瘤诊断中的评价。
IF 6.2 2区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-10-21 DOI: 10.1017/erm.2022.34
Keywan Mortezaee, Jamal Majidpoor, Fardin Fathi

Strategies for non-invasive biomarker discovery in early detection of cancer are an urgent need. Extracellular vesicles (EVs) have generated increasing attention from the scientific community and are under intensive investigations due to their unique biological profiles and their non-invasive nature. EVs are membrane-enclosed vesicles with variable sizes and function. Such vesicles are actively secreted from multiple cell types and are considered as key vehicles for inter-cellular communications and signalling. The stability and potential to easily cross biological barriers enable EVs for exerting durable effects on target cells. These along with easy access to such vesicles, the consistent secretion from tumour during all stages of tumorigenesis and their content providing a reservoir of molecules as well as mirroring the identity of the cell of origin are virtues that have made EVs appealing to be assessed in liquid biopsy approaches and for using as a promising resource of biomarkers in cancer diagnosis and therapy and monitoring targeted cancer therapy. Early detection of EVs will guide time-scheduled personalised therapy. Surveying reliable and sensitive methods for rapid isolation of EVs from biofluids, the purity of isolated vesicles and their molecular profiling and marker specification for clinical translation in patients with cancer are issues in the area and the hot topics of many recent studies. Here, the focus is over methods for EV isolation and stratification for digging more information about liquid biopsy-based diagnosis. Extending knowledge regarding EV-based strategies is a key to validate independent patient follow-up for cancer diagnosis at early stages and inspecting the efficacy of therapeutics.

在癌症的早期检测中,非侵入性生物标志物的发现是迫切需要的。细胞外囊泡(EVs)由于其独特的生物学特征和非侵入性,引起了科学界越来越多的关注,并正在进行深入的研究。EVs是膜封闭的囊泡,具有不同的大小和功能。这些囊泡从多种细胞类型中积极分泌,被认为是细胞间通信和信号传导的关键载体。电动汽车的稳定性和跨越生物屏障的潜力使其能够对靶细胞产生持久的作用。这些优点加上易于接近这些囊泡,在肿瘤发生的所有阶段从肿瘤中持续分泌,其内容提供了分子储存库,并反映了起源细胞的身份,这些优点使得电动汽车在液体活检方法中具有吸引力,并被用作癌症诊断和治疗以及监测靶向癌症治疗的生物标志物资源。早期发现电动汽车将指导及时安排的个性化治疗。寻找可靠、灵敏的方法从生物体液中快速分离出ev,分离出的囊泡的纯度及其分子谱和标记物规范用于癌症患者的临床转化是该领域的问题,也是近年来许多研究的热点。在此,重点介绍EV分离和分层方法,以挖掘更多基于液体活检的诊断信息。扩展关于基于ev的策略的知识是验证早期癌症诊断的独立患者随访和检查治疗效果的关键。
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引用次数: 3
Precision oncology using ex vivo technology: a step towards individualised cancer care? 使用离体技术的精确肿瘤学:迈向个体化癌症治疗的一步?
IF 6.2 2区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-10-03 DOI: 10.1017/erm.2022.32
Sophie T Williams, Greg Wells, Samantha Conroy, Hannah Gagg, Richard Allen, Ola Rominiyi, Thomas Helleday, Katie Hullock, Catherine E W Pennington, Juha Rantala, Spencer J Collis, Sarah J Danson

Despite advances in cancer genomics and the increased use of genomic medicine, metastatic cancer is still mostly an incurable and fatal disease. With diminishing returns from traditional drug discovery strategies, and high clinical failure rates, more emphasis is being placed on alternative drug discovery platforms, such as ex vivo approaches. Ex vivo approaches aim to embed biological relevance and inter-patient variability at an earlier stage of drug discovery, and to offer more precise treatment stratification for patients. However, these techniques also have a high potential to offer personalised therapies to patients, complementing and enhancing genomic medicine. Although an array of approaches are available to researchers, only a minority of techniques have made it through to direct patient treatment within robust clinical trials. Within this review, we discuss the current challenges to ex vivo approaches within clinical practice and summarise the contemporary literature which has directed patient treatment. Finally, we map out how ex vivo approaches could transition from a small-scale, predominantly research based technology to a robust and validated predictive tool. In future, these pre-clinical approaches may be integrated into clinical cancer pathways to assist in the personalisation of therapy choices and to hopefully improve patient experiences and outcomes.

尽管癌症基因组学取得了进展,基因组医学的使用也有所增加,但转移性癌症仍然是一种无法治愈和致命的疾病。随着传统药物发现策略的收益递减和高临床失败率,人们越来越重视替代药物发现平台,如体外方法。体外方法旨在在药物发现的早期阶段嵌入生物学相关性和患者间可变性,并为患者提供更精确的治疗分层。然而,这些技术也有很大的潜力为患者提供个性化治疗,补充和加强基因组医学。尽管研究人员可以使用一系列方法,但只有少数技术能够在可靠的临床试验中直接用于患者治疗。在这篇综述中,我们讨论了目前在临床实践中离体方法的挑战,并总结了指导患者治疗的当代文献。最后,我们描绘了离体方法如何从一个小规模的、主要基于研究的技术转变为一个强大的、经过验证的预测工具。未来,这些临床前方法可能会整合到临床癌症途径中,以帮助治疗选择的个性化,并有望改善患者的体验和结果。
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引用次数: 2
The compartmentalised nature of neuronal mitophagy: molecular insights and implications. 神经元自噬的区隔性质:分子的见解和意义。
IF 6.2 2区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-09-29 DOI: 10.1017/erm.2022.31
Fivos Borbolis, Konstantinos Palikaras

The maintenance of a healthy mitochondrial network and the ability to adjust organelle population in response to internal or external stimuli are essential for the function and the survival of eukaryotic cells. Over the last two decades several studies have demonstrated the paramount importance of mitophagy, a selective form of autophagy that removes damaged and/or superfluous organelles, in organismal physiology. Post-mitotic neuronal cells are particularly vulnerable to mitochondrial damage, and mitophagy impairment has emerged as a causative factor in multiple neurodegenerative pathologies, including Alzheimer's disease and Parkinson's disease among others. Although mitochondrial turnover is a multifaceted process, neurons have to tackle additional complications, arising from their pronounced bioenergetic demands and their unique architecture and cellular polarisation that render the degradation of distal organelles challenging. Mounting evidence indicates that despite the functional conservation of mitophagy pathways, the unique features of neuronal physiology have led to the adaptation of compartmentalised solutions, which serve to ensure seamless mitochondrial removal in every part of the cell. In this review, we summarise the current knowledge concerning the molecular mechanisms that mediate mitophagy compartmentalisation and discuss their implications in various human pathologies.

维持健康的线粒体网络和调节细胞器数量以响应内部或外部刺激的能力对真核细胞的功能和存活至关重要。在过去的二十年里,一些研究已经证明了有丝自噬(一种选择性的自噬形式,可以去除受损和/或多余的细胞器)在有机体生理学中的重要作用。有丝分裂后的神经元细胞特别容易受到线粒体损伤,线粒体自噬损伤已成为多种神经退行性疾病的致病因素,包括阿尔茨海默病和帕金森病等。尽管线粒体更新是一个多方面的过程,但神经元必须解决额外的复杂性,这些复杂性来自于它们明显的生物能量需求,以及它们独特的结构和细胞极化,这使得远端细胞器的降解具有挑战性。越来越多的证据表明,尽管线粒体自噬途径的功能守恒,但神经元生理的独特特征导致了区隔化解决方案的适应,这有助于确保细胞每个部分的线粒体无缝去除。在这篇综述中,我们总结了目前关于介导有丝分裂区隔化的分子机制的知识,并讨论了它们在各种人类病理中的意义。
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引用次数: 2
Roles of CCR10/CCL27-CCL28 axis in tumour development: mechanisms, diagnostic and therapeutic approaches, and perspectives. CCR10/CCL27-CCL28轴在肿瘤发展中的作用:机制、诊断和治疗方法及观点
IF 6.2 2区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-09-26 DOI: 10.1017/erm.2022.28
Ermias Mergia Terefe, Maria Jade Catalan Opulencia, Amir Rakhshani, Mohammad Javed Ansari, Sergushina Elena Sergeevna, Sura A Awadh, Djamila Sh Polatova, Adnan Hashim Abdulkadhim, Yasser Fakri Mustafa, Hamzah H Kzar, Moaed E Al-Gazally, Mustafa M Kadhim, Gholamali Taherian

Cancer is now one of the major causes of death across the globe. The imbalance of cytokine and chemokine secretion has been reported to be involved in cancer development. Meanwhile, CC chemokines have received considerable interest in cancer research. CCR10, as the latest identified CC chemokine receptor (CCR), has been implicated in the recruitment and infiltration of immune cells, especially lymphocytes, into epithelia such as skin via ligation to two ligands, CCL27 and CCL28. Other than homoeostatic function, several mechanisms have been shown to dysregulate CCR10/CCL27-CCL28 expression in the tumour microenvironment. As such, these receptors and ligands mediate T-cell trafficking in the tumour microenvironment. Depending on the types of lymphocytes recruited, CCR10/CCL27-CCL28 interaction has been shown to play conflicting roles in cancer development. If they were T helper and cytotoxic T cells and natural killer cells, the role of this axis would be tumour-suppressive. In contrast, if CCR10/CCL27-CCL28 recruited regulatory T cells, cancer-associated fibroblasts or myeloid-derived suppressor cells, it would lead to tumour progression. In addition to the trafficking of lymphocytes and immune cells, CCR10 also leads to the migration of tumour cells or endothelial cells (called angiogenesis and lymphangiogenesis) to promote tumour metastasis. Furthermore, CCR10 signalling triggers tumour-promoting signalling such as PI3K/AKT and mitogen-activated protein kinase/extracellular signal-regulated kinase, resulting in tumour cell growth. Since CCR10/CCL27-CCL28 is dysregulated in the tumour tissues, it is suggested that analysis and measurement of them might predict tumour development. Finally, it is hoped using therapeutic approaches based on this axis might increase our knowledge to overcome tumour progression.

癌症现在是全球死亡的主要原因之一。据报道,细胞因子和趋化因子分泌的不平衡与癌症的发生有关。同时,CC趋化因子在癌症研究中引起了相当大的兴趣。CCR10是最新发现的CC趋化因子受体(CCR),通过连接两种配体CCL27和CCL28,参与免疫细胞(尤其是淋巴细胞)向皮肤等上皮细胞的募集和浸润。除了稳态功能外,肿瘤微环境中CCR10/CCL27-CCL28表达失调有多种机制。因此,这些受体和配体介导t细胞在肿瘤微环境中的运输。根据募集淋巴细胞的类型,CCR10/CCL27-CCL28相互作用已被证明在癌症发展中发挥相互矛盾的作用。如果它们是T辅助细胞、细胞毒性T细胞和自然杀伤细胞,那么这个轴的作用将是抑制肿瘤。相反,如果CCR10/CCL27-CCL28募集调节性T细胞、癌症相关成纤维细胞或髓源性抑制细胞,则会导致肿瘤进展。除了淋巴细胞和免疫细胞的运输,CCR10还导致肿瘤细胞或内皮细胞(称为血管生成和淋巴管生成)的迁移,以促进肿瘤转移。此外,CCR10信号传导触发肿瘤促进信号传导,如PI3K/AKT和丝裂原活化蛋白激酶/细胞外信号调节激酶,导致肿瘤细胞生长。由于CCR10/CCL27-CCL28在肿瘤组织中表达异常,因此分析和测量CCR10/CCL27-CCL28可以预测肿瘤的发展。最后,希望利用基于这一轴的治疗方法可以增加我们克服肿瘤进展的知识。
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引用次数: 2
Regulatory role of JMJD6 in placental development. JMJD6在胎盘发育中的调控作用。
IF 6.2 2区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-09-19 DOI: 10.1017/erm.2022.30
Xiaoli Shen, Christian De Geyter, Hong Zhang, Guoning Huang

Correct placental development and function are critical to both the mother's and the foetus' health during pregnancy. Placental function depends on the correct development of the vascular network, which requires proper angiogenesis. Impaired angiogenesis in the placenta can induce foetal growth restriction, preeclampsia, and even foetal death. Placental angiogenesis is finely controlled by ubiquitous and pregnancy-specific angiogenic factors. Jumonji domain-containing protein 6 (JMJD6) is a Fe (II)- and 2-oxoglutarate (2OG)-dependent oxygenase that catalyses arginine demethylation and lysine hydroxylation of histone and non-histone peptides. JMJD6 has been implicated in embryonic development, cellular proliferation and migration, self-tolerance induction in the thymus, and adipocyte differentiation. In this review we present JMJD6's structure and activity, as well as its role in angiogenesis, oxygen sensing, and adverse pregnancy outcomes related to placental development. Understanding the interaction between JMJD6 and other placental factors may identify potential therapeutic targets for correcting abnormal placental angiogenesis and function.

在怀孕期间,正确的胎盘发育和功能对母亲和胎儿的健康都至关重要。胎盘的功能取决于血管网络的正确发育,这需要适当的血管生成。胎盘血管生成受损可导致胎儿生长受限、子痫前期,甚至胎儿死亡。胎盘血管生成受到普遍存在的和妊娠特异性血管生成因子的精细控制。Jumonji结构域蛋白6 (JMJD6)是一种铁(II)和2-氧葡萄糖酸酯(2OG)依赖的加氧酶,可催化组蛋白和非组蛋白肽的精氨酸去甲基化和赖氨酸羟基化。JMJD6参与胚胎发育、细胞增殖和迁移、胸腺自我耐受诱导和脂肪细胞分化。在这篇综述中,我们介绍了JMJD6的结构和活性,以及它在血管生成、氧传感和与胎盘发育相关的不良妊娠结局中的作用。了解JMJD6与其他胎盘因子之间的相互作用,可以找到纠正胎盘血管生成和功能异常的潜在治疗靶点。
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引用次数: 1
Possibilities of using T-cell biophysical biomarkers of ageing. 使用老化 T 细胞生物物理生物标志物的可能性。
IF 4.5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-09-16 DOI: 10.1017/erm.2022.29
Blanca González-Bermúdez, Aldo Abarca-Ortega, Mónica González-Sánchez, Mónica De la Fuente, Gustavo R Plaza

Ageing is interrelated with the development of immunosenescence. This article focuses on one of the cell sets of the adaptive immune system, T cells, and provides a review of the known changes in T cells associated with ageing. Such fundamental changes affect both cell molecular content and internal ordering. However, acquiring a complete description of the changes at these levels would require extensive measurements of parameters and, furthermore, important fine details of the internal ordering that may be difficult to detect. Therefore, an alternative approach for the characterisation of cells consists of the performance of physical measurements of the whole cell, such as deformability measurements or migration measurements: the physical parameters, complementing the commonly used chemical biomarkers, may contribute to a better understanding of the evolution of T-cell states during ageing. Mechanical measurements, among other biophysical measurements, have the advantage of their relative simplicity: one single parameter agglutinates the complex effects of the variety of changes that gradually appear in cells during ageing.

衰老与免疫衰老的发展相互关联。本文将重点关注适应性免疫系统的细胞组之一--T 细胞,并对已知的与衰老相关的 T 细胞变化进行综述。这种根本性的变化会影响细胞的分子含量和内部排序。然而,要完整描述这些层面的变化,需要对参数进行大量测量,而且内部排序的重要细节可能难以检测到。因此,细胞表征的另一种方法是对整个细胞进行物理测量,如变形性测量或迁移测量:物理参数与常用的化学生物标记互为补充,有助于更好地了解老化过程中 T 细胞状态的演变。机械测量与其他生物物理测量一样,具有相对简单的优点:一个单一参数就能凝集细胞老化过程中逐渐出现的各种变化的复杂影响。
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引用次数: 0
Unveil the pain of endometriosis: from the perspective of the nervous system. 揭开子宫内膜异位症的痛苦:从神经系统的角度。
IF 6.2 2区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-09-05 DOI: 10.1017/erm.2022.26
Peiya Fan, Tian Li

Endometriosis is a chronic inflammatory disease with pelvic pain and uncharacteristic accompanying symptoms. Endometriosis-associated pain often persists despite treatment of the disease, thus it brings a deleterious impact on their personal lives as well as imposing a substantial economic burden on them. At present, mechanisms underlie endometriosis-associated pain including inflammatory reaction, injury, aberrant blood vessels and the morphological and functional anomaly of the peripheral and central nervous systems. The nerve endings are influenced by the physical and chemical factors surrounding the lesion, via afferent nerve to the posterior root of the spinal nerve, then to the specific cerebral cortex involved in nociception. However, our understanding of the aetiology and mechanism of this complex pain process caused by endometriosis remains incomplete. Identifying the pathogenesis of endometriosis is crucial to disease management, offering proper treatment, and helping patients to seek novel targets for the maintenance and contributors of chronic pain. The main aim of this review is to focus on every possible mechanism of pain related to endometriosis in both peripheral and central nervous systems, and to present related mechanisms of action from the interaction between peripheral lesions and nerves to the changes in transmission of pain, resulting in hyperalgesia and the corresponding alterations in cerebral cortex and brain metabolism.

子宫内膜异位症是一种慢性炎症性疾病,伴有骨盆疼痛和非特征性的伴随症状。子宫内膜异位症相关的疼痛通常持续存在,尽管该疾病的治疗,因此它带来了有害的影响,对他们的个人生活以及施加了巨大的经济负担。目前,子宫内膜异位症相关疼痛的机制包括炎症反应、损伤、血管异常以及外周和中枢神经系统的形态和功能异常。神经末梢受病变周围的物理和化学因素影响,经传入神经到脊神经后根,再到参与伤害感觉的特定大脑皮层。然而,我们对这种由子宫内膜异位症引起的复杂疼痛过程的病因和机制的理解仍然不完整。确定子宫内膜异位症的发病机制对疾病管理、提供适当的治疗以及帮助患者寻找维持慢性疼痛的新靶点至关重要。本文主要从外周神经系统和中枢神经系统两方面对子宫内膜异位症相关疼痛的可能机制进行综述,并从外周病变与神经的相互作用到疼痛传递的改变,从而导致痛觉过敏以及相应的大脑皮层和脑代谢的改变,提出相关的作用机制。
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引用次数: 1
Mismatch repair is a double-edged sword in the battle against microsatellite instability. 错配修复是对抗微卫星不稳定性的一把双刃剑。
IF 6.2 2区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-09-05 DOI: 10.1017/erm.2022.16
Carson J Miller, Karen Usdin

Roughly 3% of the human genome consists of microsatellites or tracts of short tandem repeats (STRs). These STRs are often unstable, undergoing high-frequency expansions (increases) or contractions (decreases) in the number of repeat units. Some microsatellite instability (MSI) is seen at multiple STRs within a single cell and is associated with certain types of cancer. A second form of MSI is characterised by expansion of a single gene-specific STR and such expansions are responsible for a group of 40+ human genetic disorders known as the repeat expansion diseases (REDs). While the mismatch repair (MMR) pathway prevents genome-wide MSI, emerging evidence suggests that some MMR factors are directly involved in generating expansions in the REDs. Thus, MMR suppresses some forms of expansion while some MMR factors promote expansion in other contexts. This review will cover what is known about the paradoxical effect of MMR on microsatellite expansion in mammalian cells.

大约3%的人类基因组由微卫星或短串联重复序列(STRs)组成。这些str通常不稳定,在重复单元的数量上经历高频扩张(增加)或收缩(减少)。一些微卫星不稳定性(MSI)见于单个细胞内的多个STRs,并与某些类型的癌症有关。第二种形式的MSI的特征是单个基因特异性STR的扩增,这种扩增导致40多种人类遗传疾病,称为重复扩增病(red)。虽然错配修复(MMR)途径阻止了全基因组的MSI,但新出现的证据表明,一些MMR因素直接参与了red中扩增的产生。因此,MMR抑制某些形式的扩张,而一些MMR因素在其他情况下促进扩张。这篇综述将涵盖已知的MMR对哺乳动物细胞中微卫星扩增的矛盾效应。
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引用次数: 1
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