Mutation Research-Reviews in Mutation Research最新文献_第3页

Neurogenetic biomarkers in epilepsy: A comprehensive narrative review of progression and therapeutic approaches 癫痫的神经遗传生物标志物：进展和治疗方法的综合叙述综述

IF 4.2 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research

Pub Date : 2025-07-01 DOI: 10.1016/j.mrrev.2025.108556

Ramandeep Kaur Sidhu , Kousik Maparu , Khadga Raj Aran

Epilepsy is a multifaceted and heterogenous neurological disorder that affects an estimated 70 million people worldwide and is identified by recurrent or unprovoked seizure activity. Although there have been advances in pharmacotherapeutic treatments, approximately one-third of patients with epilepsy remain drug resistant, highlighting the need for personalised and mechanism-based strategies. Neurogenetic biomarkers are emerging as valuable instruments for translating the genetic findings to the bedside and may provide new opportunities within a more precise treatment paradigm in epilepsy. Neurogenetic biomarkers include single-nucleotide polymorphisms (SNPs), copy number variants (CNVs), and mutations in disease-specific genes that inform our knowledge about the genetic architecture of seizure susceptibility, seizure progression and therapeutic response. The main genes, such as SCN1A, KCNQ2, GRIN2A, LGI1, GABRA1, and CHRNA4, impact neuronal excitability, ion channel dynamics, and synaptic interactions. Variations of mTOR signaling pathways (TSC1, TSC2, DEPDC5) and mutations in epigenetic regulators (MECP2, CDKL5) implicated a multilayered structure in the mechanistic underpinnings of epileptogenesis. Neurogenetic biomarkers are increasingly relevant to clinical practice for refining diagnosis, predicting seizure onset, guiding drug selection, and determining surgical intervention. The integration of neurogenetic sampling with neuroimaging, electrophysiological, inflammatory, and molecular signatures can improve diagnostic precision and provide an evidence-based framework towards therapeutic stratification. Although challenges remain-such as genetic heterogeneity, variant interpretation, cost barriers, and ethical considerations, advances in next-generation sequencing, pharmacogenomics, and artificial intelligence are rapidly transforming these limitations into opportunities. Neurogenetic biomarkers hold transformative potential to redefine epilepsy care, enabling earlier diagnosis, individualized therapy, and improved long-term outcomes. As the field advances, they are poised to shift epilepsy management from reactive to predictive, and from generalized to precision-driven, initiating a new era of neurology.

癫痫是一种多面性和异质性的神经系统疾病，影响全世界约7000万人，可通过反复发作或无端发作活动确诊。尽管在药物治疗方面取得了进展，但大约三分之一的癫痫患者仍然具有耐药性，这凸显了个性化和基于机制的策略的必要性。神经遗传生物标志物正在成为将遗传发现转化为床边的有价值的工具，并可能在更精确的癫痫治疗范式中提供新的机会。神经遗传生物标志物包括单核苷酸多态性（SNPs）、拷贝数变异（CNVs）和疾病特异性基因突变，这些基因可以帮助我们了解癫痫易感性、癫痫进展和治疗反应的遗传结构。主要基因，如SCN1A、KCNQ2、GRIN2A、LGI1、GABRA1和CHRNA4，影响神经元的兴奋性、离子通道动力学和突触相互作用。mTOR信号通路（TSC1、TSC2、DEPDC5）的变化和表观遗传调控因子（MECP2、CDKL5）的突变暗示了癫痫发生机制基础的多层结构。神经遗传生物标志物与临床实践的关系日益密切，可用于精炼诊断、预测癫痫发作、指导药物选择和确定手术干预。神经遗传学采样与神经影像学、电生理、炎症和分子特征的结合可以提高诊断精度，并为治疗分层提供循证框架。尽管挑战仍然存在，如遗传异质性、变异解释、成本障碍和伦理考虑，但下一代测序、药物基因组学和人工智能的进步正在迅速将这些限制转化为机遇。神经遗传生物标志物具有重新定义癫痫治疗的变革性潜力，能够实现早期诊断、个体化治疗和改善长期结果。随着该领域的发展，他们准备将癫痫管理从反应性转变为预测性，从广义转变为精确驱动，开启神经病学的新时代。

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引用次数: 0

Non-coding RNAs in Wilson’s Disease: Plausible drivers of hepatic symptom heterogeneity 肝豆状核变性中的非编码rna：肝脏症状异质性的合理驱动因素

IF 4.2 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research

Pub Date : 2025-07-01 DOI: 10.1016/j.mrrev.2025.108570

Neelanjana Sarkar , Arpan Saha , Shubhrajit Roy , Mainak Sengupta

Wilson’s disease (WD) is an autosomal recessive disorder caused by mutations in the ATP7B gene, which impair cellular copper excretion and lead to toxic copper accumulation in the liver, brain, and other organs. Clinically, WD presents with a broad spectrum of hepatic and neurological manifestations. The pronounced phenotypic variability among patients harboring identical ATP7B mutations, including affected siblings, suggests the influence of additional genetic and/or epigenetic factors such as non-coding RNAs (ncRNAs), in modulating disease presentation. This review explores the potential involvement of ncRNAs in shaping the hepatic phenotype of WD. Although a few transcriptomic and network-based studies in mouse models have underscored the relevance of ncRNAs in WD pathogenesis, there remains a paucity of research investigating their role in the spectrum of hepatic severity observed in human patients. To address this gap, we collated existing evidence on ncRNAs implicated in WD and further sought to predict additional candidate ncRNAs by aligning hepatic severity categories in WD with general liver diseases that exhibit similar clinical features. Through a systematic literature review, we identified dysregulated ncRNAs in these liver diseases that may serve as surrogates for WD severity groups. Furthermore, our in silico analyses highlighted several microRNAs (miRNAs) that, if upregulated, could downregulate ATP7B or its putative modifier genes, raising the possibility that miRNA dysregulation may phenocopy certain pathogenic effects of ATP7B mutations, especially in WD cases exhibiting missing heritability.

威尔逊氏病（WD）是一种常染色体隐性遗传病，由ATP7B基因突变引起，其损害细胞铜排泄并导致有毒铜在肝脏、大脑和其他器官的积累。临床上，WD表现为广泛的肝脏和神经系统表现。具有相同ATP7B突变的患者（包括受影响的兄弟姐妹）明显的表型变异性表明，其他遗传和/或表观遗传因素（如非编码rna (ncRNAs)）在调节疾病表现方面具有影响。这篇综述探讨了ncrna在塑造WD肝脏表型中的潜在参与。尽管在小鼠模型中进行的一些转录组学和基于网络的研究强调了ncrna在WD发病机制中的相关性，但在人类患者中观察到的肝脏严重程度谱中，仍缺乏研究调查ncrna的作用。为了解决这一差距，我们整理了与WD相关的ncrna的现有证据，并通过将WD的肝脏严重程度类别与表现出相似临床特征的一般肝脏疾病相比较，进一步寻求预测其他候选ncrna。通过系统的文献回顾，我们在这些肝脏疾病中发现了失调的ncrna，可以作为WD严重程度组的替代指标。此外，我们的计算机分析强调了几种microrna (miRNA)，如果上调，可以下调ATP7B或其假定的修饰基因，这增加了miRNA失调可能表型ATP7B突变的某些致病作用的可能性，特别是在缺乏遗传力的WD病例中。

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引用次数: 0

Systematic review on toxicological effects of platinum nanoparticles: Towards their use as safe biomedical tools 铂纳米颗粒毒理学效应的系统综述：迈向其作为安全生物医学工具的应用

IF 4.2 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research

Pub Date : 2025-07-01 DOI: 10.1016/j.mrrev.2025.108554

Assia Touzani , Lucía Ramos-Pan , Sónia Fraga , Natalia Fernández-Bertólez , Blanca Laffon , Vanessa Valdiglesias

Platinum nanoparticles (PtNP) have received considerable attention in the nanomedicine field due to their magnetic, catalytic, and optical properties. However, the potential toxicity of PtNP has not been properly evaluated yet, and current information on the possible risks related to their use is still limited. On this basis, the main objective of this systematic review was to gather available data on PtNP biological behaviour and potential harmful effects, as well as to highlight the gaps of knowledge that need to be filled in to progress in their use in clinical practice. A total of 441 studies were obtained and reviewed from the initial search; 108 fulfilled the selection criteria and were included in the revision. Mainly in vitro but also in vivo studies were reported using a variety of biological systems and animal models, with no data from human epidemiological studies published so far. All these studies were extensively evaluated to provide useful information on the PtNP biocompatibility and their potential to be employed for medical purposes. In particular, information on the physicochemical features of the PtNP influencing their biological behaviour, methods employed for toxicity evaluation, biological systems used, and outcomes addressed were analysed and discussed. In general, the results obtained showed a good biocompatibility of these NP, although some of them detected significant toxicity highly dependent of size, concentration/dose, coating, or exposed biological system. Furthermore, anticancer or protective effects were also described for PtNP in several revised studies. These findings encourage to continue exploring the benefits of PtNP for clinical practice.

铂纳米粒子（PtNP）由于其磁性、催化性和光学性质在纳米医学领域受到了广泛的关注。然而，PtNP的潜在毒性尚未得到适当评价，目前关于其使用可能带来的风险的信息仍然有限。在此基础上，本系统综述的主要目的是收集有关PtNP生物学行为和潜在有害影响的现有数据，并强调需要填补的知识空白，以促进其在临床实践中的应用。从最初的检索中共获得并审查了441项研究；108个符合选择标准，列入订正。主要是体外研究，也有使用多种生物系统和动物模型的体内研究报告，迄今尚未发表来自人类流行病学研究的数据。所有这些研究都进行了广泛的评估，以提供有关PtNP生物相容性及其用于医疗目的的潜力的有用信息。特别是分析和讨论了影响PtNP生物行为的物理化学特征、毒性评估方法、使用的生物系统和处理的结果等信息。总的来说，获得的结果显示这些NP具有良好的生物相容性，尽管其中一些检测到明显的毒性，高度依赖于尺寸，浓度/剂量，涂层或暴露的生物系统。此外，在一些修订的研究中也描述了PtNP的抗癌或保护作用。这些发现鼓励继续探索PtNP在临床实践中的益处。

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引用次数: 0

Genetic variations in zona pellucida glycoproteins: Implications for fertility and ART outcomes 透明带糖蛋白的遗传变异：对生育和抗逆转录病毒治疗结果的影响

IF 4.2 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research

Pub Date : 2025-07-01 DOI: 10.1016/j.mrrev.2025.108560

Neha Rajput, Gagandeep Kaur Gahlay

The success of Assisted Reproductive Technologies (ART), such as IVF and ICSI, relies heavily on the health of the oocyte, with abnormalities in oocyte morphology often leading to ART failure. The zona pellucida (ZP), an extracellular matrix surrounding the oocyte, plays a crucial role in sperm-egg recognition, species-specific fertilization, and protecting the embryo until implantation. This article investigates the impact of single nucleotide polymorphisms (SNPs) in the genes encoding ZP glycoproteins (hZP1, hZP2, hZP3, and hZP4) on fertility. Through a comprehensive meta-analysis of existing data, we identified 47 SNPs in hZP1, 17 in hZP2, 8 in hZP3, and 2 in hZP4 from female patients undergoing infertility treatment. Most of these SNPs are localized within the zona domain, which is crucial for the polymerization and structural integrity of the ZP. Functional predictions, based on in silico tools, suggest that these SNPs lead to impaired ZP glycoprotein secretion, crosslinking, and fibril formation; resulting in conditions like empty follicle syndrome (EFS) or oocytes with a thin or absent ZP. These deficiencies could significantly affect oocyte viability and reduce ART success rates. It could also affect folliculogenesis. Our results highlight the importance of genetic screening in women experiencing ART failure, especially those with ZP abnormalities. Additionally, the absence of reported SNPs in the N-terminal domain of ZP2 which is crucial for sperm interaction, suggests a potential area for further investigation, particularly in morphologically normal oocytes that may harbor undetected SNPs.

辅助生殖技术（ART）的成功，如IVF和ICSI，在很大程度上依赖于卵母细胞的健康，卵母细胞形态异常往往导致ART失败。透明带（ZP）是围绕卵母细胞的细胞外基质，在精子-卵子识别、物种特异性受精和胚胎着床前的保护中起着至关重要的作用。本文研究了编码ZP糖蛋白（hZP1, hZP2， hZP3和hZP4）基因的单核苷酸多态性（snp）对生育能力的影响。通过对现有数据的综合荟萃分析，我们从接受不孕症治疗的女性患者中发现了47个hZP1 snp， 17个hZP2 snp， 8个hZP3 snp， 2个hZP4 snp。这些snp大多定位在带域内，这对ZP的聚合和结构完整性至关重要。基于硅工具的功能预测表明，这些snp导致ZP糖蛋白分泌、交联和原纤维形成受损；导致空卵泡综合征（EFS）或卵母细胞ZP薄或缺失。这些缺陷会显著影响卵母细胞活力，降低抗逆转录病毒治疗的成功率。它还可能影响卵泡生成。我们的研究结果强调了基因筛查在抗逆转录病毒治疗失败的女性中的重要性，尤其是那些有ZP异常的女性。此外，在ZP2的n端结构域中缺乏对精子相互作用至关重要的SNPs，这表明了一个潜在的进一步研究领域，特别是在形态正常的卵母细胞中，可能存在未检测到的SNPs。

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引用次数: 0

Rett syndrome: Pathogenicity and regulation of MECP2 (human) and Mecp2 (mouse) genes and their protein products through various molecular mechanisms Rett综合征：MECP2（人）和MECP2（小鼠）基因及其蛋白产物通过多种分子机制的致病性和调控

IF 6.4 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research

Pub Date : 2025-07-01 DOI: 10.1016/j.mrrev.2025.108553

Bashir Ahmad , John Sieh Dumbuya , Ji-Xin Tang , Wen Li , Xiuling Chen , Jun Lu

Rett syndrome was first described over 50 years ago as an unusual clinical entity. Mutations in the X-linked MECP2 gene are the primary causes of Rett syndrome. The unstructured MeCP2 protein adopts various functional conformations, complicating its study. Researchers have investigated the pathogenicity and regulation of MECP2 through mechanisms such as apoptosis, mitophagy, the PI3K/AKT/mTOR pathway, BMP signaling, NF-kB, STAT3, and the Wnt/β-catenin pathway. These mechanisms have not been reviewed in such detail before. Summarizing these pathways is essential for facilitating further exploration by researchers; therefore, we have comprehensively summarized these pathways.

Rett综合征在50多年前首次被描述为一种不寻常的临床实体。x连锁MECP2基因的突变是Rett综合征的主要原因。非结构化MeCP2蛋白具有多种功能构象，使其研究复杂化。研究人员通过凋亡、有丝分裂、PI3K/AKT/mTOR通路、BMP信号通路、NF-kB、STAT3和Wnt/β-catenin通路等机制研究了MECP2的致病性和调控作用。这些机制以前从未被如此详细地审查过。总结这些途径对于促进研究人员进一步探索至关重要；因此，我们对这些途径进行了全面总结。

引用次数: 0

Trichothiodystrophy: Molecular insights and mechanisms of pathogenicity 毛硫营养不良：分子见解和致病性机制

IF 4.2 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research

Pub Date : 2025-07-01 DOI: 10.1016/j.mrrev.2025.108555

Manuela Lanzafame, Francesca Brevi, Gaia Veniali, Elena Botta

Trichothiodystrophy (TTD) is a rare hereditary disease characterized by brittle, sulphur deficient hair associated with a wide and varied spectrum of clinical features which include skin alterations, neurodevelopmental defects, and immune dysfunction. The presence of hypersensitivity to UV light defines the two main forms of TTD: photosensitive (PS-TTD) and non-photosensitive (NPS-TTD). The disease arises from mutations in a variety of genes involved in different biological processes. Affected processes include DNA repair, transcription as well as translation. This review provides the latest vision of TTD: from up-to-date mutational spectra and genotype-phenotype relationships to our current understanding of the pathogenic mechanisms that underlie the complex etiology of this multi-faceted disease.

毛硫营养不良（TTD）是一种罕见的遗传性疾病，其特征是头发变脆，缺硫，并伴有多种临床特征，包括皮肤改变，神经发育缺陷和免疫功能障碍。对紫外线超敏的存在定义了两种主要形式的TTD：光敏（PS-TTD）和非光敏（NPS-TTD）。这种疾病是由参与不同生物过程的多种基因突变引起的。受影响的过程包括DNA修复、转录和翻译。这篇综述提供了TTD的最新视野：从最新的突变谱和基因型-表型关系到我们目前对这种多方面疾病复杂病因的致病机制的理解。

引用次数: 0

KRAS oncogenic mutations in benign tumors: adenomatoid odontogenic tumor as a model 良性肿瘤中的KRAS致癌突变：以腺瘤样牙源性肿瘤为模型

IF 6.4 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research

Pub Date : 2025-07-01 DOI: 10.1016/j.mrrev.2025.108552

Bruna Pizziolo Coura , Letícia Martins Guimarães , Ricardo Santiago Gomez , Carolina Cavaliéri Gomes

The KRAS protein is a GTPase that plays a role in the MAPK/ERK signaling pathway and KRAS is one of the most frequently mutated proto-oncogenes in malignant neoplasms, including aggressive tumors such as lung, pancreatic, and colorectal cancer. Mutations in KRAS, previously considered oncogenic drivers and hallmarks of cancer, have been observed at a high frequency in benign sporadic tumors, including those with negligible potential for malignant transformation. In line with that, KRAS mutations have recently been shown to be highly prevalent in adenomatoid odontogenic tumor (AOT). In the present paper, we review the spectrum of KRAS mutations reported in AOT to date and discuss the context dependence of KRAS oncogenicity. KRAS p.G12V and p.G12R mutations have been reported in approximately 70 % of AOT cases. The fact that the same spectrum of KRAS mutations is found in tumors with diverse clinical behavior reinforces the tissue and context specificity of KRAS mutation effects. Genome-wide-based future studies may provide clarification on the molecular pathogenesis of the KRAS wild-type cases, and could potentially unravel additional genetic events in mutation-positive cases. In this scenario, the clarification of the molecular pathogenesis of AOT, a benign tumor of indolent behavior, sheds light into how KRAS oncogenic mutations exert distinct effects depending on the biological context.

KRAS蛋白是一种GTPase，在MAPK/ERK信号通路中起作用，KRAS是恶性肿瘤中最常见的突变原癌基因之一，包括肺癌、胰腺癌和结直肠癌等侵袭性肿瘤。KRAS的突变，以前被认为是致癌驱动因素和癌症的标志，已经在良性散发性肿瘤中观察到很高的频率，包括那些恶性转化的可能性可以忽略不计的肿瘤。与此一致的是，KRAS突变最近被证明在腺瘤样牙源性肿瘤（AOT）中非常普遍。在本文中，我们回顾了迄今为止在AOT中报道的KRAS突变谱，并讨论了KRAS致癌性的环境依赖性。据报道，KRAS p.G12V和p.G12R突变约占AOT病例的70% %。在具有不同临床行为的肿瘤中发现相同的KRAS突变谱，这一事实加强了KRAS突变效应的组织和背景特异性。基于全基因组的未来研究可能会澄清KRAS野生型病例的分子发病机制，并可能在突变阳性病例中揭示其他遗传事件。在这种情况下，AOT（一种惰性行为的良性肿瘤）的分子发病机制的阐明，揭示了KRAS致癌突变如何根据生物学背景发挥不同的作用。

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引用次数: 0

All roads lead to mitosis: A common requirement for DNA replication stress-dependent and -independent killing of BRCA-deficient cells. 所有的途径都会导致有丝分裂：这是DNA复制的一个共同要求，即应激依赖性和brca缺陷细胞的独立杀伤。

IF 4.2 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research

Pub Date : 2025-07-01 Epub Date: 2025-07-30 DOI: 10.1016/j.mrrev.2025.108557

Sebastian Omar Siri, Ariel Abramovici Blasco, Ginette Moyano, María Candelaria Mares Ahlers, Vanesa Gottifredi

The deficiency in breast cancer associated proteins 1 and 2 (BRCA1 and 2) causes an early and more frequent onset of tumor genesis and progression. Poly (ADP-ribose) polymerase inhibitors (PARPi) are selectively toxic towards BRCA1 and 2-deficient tumors, sparing the healthy cells from patients from side effects. In BRCA1 and 2 deficient tumors, PARPi-mediated cell death is characterized by the augmentation of replication stress (RS) and chromosome instability (CIN) including micronuclei (MN) accumulation, a source of swift genomic rearrangements. PARPi also cause resistance to treatments which indicates the need of treatment alternatives. In this review, we discuss potential options that, similarly to PARPi, selectively kill BRCA1 and/or 2 deficient tumors. Remarkably, while many of those alternatives also upregulate MN and other CIN variables, others cause a RS-independent and MN-independent cell killing. This is the case of the inhibitors of Rho-kinase (ROCK) and, potentially, mitotic kinase Polo like kinase 1 (PLK1). Such a mode of cell killing could be advantageous if attempting to either prevent or postpone the rise of resistance clones in the tumor population that survives the treatment.

乳腺癌相关蛋白1和2 （BRCA1和2）的缺乏导致肿瘤发生和发展的早期和更频繁的发作。聚（adp -核糖）聚合酶抑制剂（PARPi）对BRCA1和2缺陷肿瘤具有选择性毒性，使患者的健康细胞免受副作用的影响。在BRCA1和2缺陷肿瘤中，parpi介导的细胞死亡的特征是复制应激（RS）和染色体不稳定性（CIN）的增强，包括微核（MN）积累，这是快速基因组重排的来源。PARPi还引起对治疗的耐药性，这表明需要替代治疗。在这篇综述中，我们讨论了潜在的选择，类似于PARPi，选择性地杀死BRCA1和/或2缺陷肿瘤。值得注意的是，虽然许多这些替代方案也上调MN和其他CIN变量，但其他替代方案会导致rs独立和MN独立的细胞杀伤。rho激酶（ROCK）和有丝分裂激酶Polo样激酶1 （PLK1）的抑制剂就是这种情况。如果试图阻止或推迟在治疗后存活的肿瘤群体中耐药克隆的增加，这种细胞杀伤模式可能是有利的。

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引用次数: 0

LRP1B in cancer: From a mutation landscape to predictive biomarkers for precision oncology 癌症中的LRP1B：从突变景观到精确肿瘤学的预测性生物标志物。

IF 4.2 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research

Pub Date : 2025-07-01 DOI: 10.1016/j.mrrev.2025.108568

Likun Yang , Ximo Wang , Xiangyang Yu , Jing Xun

Low-density lipoprotein receptor-related protein 1B (LRP1B) is one of the most frequently mutated genes across a wide range of malignancies and has garnered increasing attention owing to its crucial role in tumorigenesis and clinical outcomes. Emerging evidence suggests that LRP1B mutations not only disrupt essential cellular processes such as proliferation, migration, and genomic stability but also significantly impact antigen presentation, modulation of the tumor immune microenvironment, and responses to immunotherapy. These findings highlight its substantial biological and clinical significance. Notably, the mutational landscape of LRP1B exhibits marked tissue specificity and molecular subtype heterogeneity, which may influence the efficacy of immunotherapy, targeted therapies, and cytotoxic chemotherapy. In this review, we provide a comprehensive overview of the mutation patterns, mechanistic functions, immunological roles, and therapeutic predictive value of LRP1B across various cancer types, with the aim of supporting its development as a biomarker and therapeutic target in precision oncology.

低密度脂蛋白受体相关蛋白1B （LRP1B）是多种恶性肿瘤中最常发生突变的基因之一，由于其在肿瘤发生和临床结果中的关键作用而受到越来越多的关注。新出现的证据表明，LRP1B突变不仅破坏了增殖、迁移和基因组稳定性等基本细胞过程，而且显著影响抗原呈递、肿瘤免疫微环境的调节和对免疫治疗的反应。这些发现突出了其重要的生物学和临床意义。值得注意的是，LRP1B的突变格局表现出明显的组织特异性和分子亚型异质性，这可能会影响免疫治疗、靶向治疗和细胞毒性化疗的疗效。在这篇综述中，我们全面概述了LRP1B的突变模式、机制功能、免疫学作用和治疗预测价值，旨在支持其作为精确肿瘤的生物标志物和治疗靶点的发展。

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引用次数: 0

Acute and chronic inflammation in firefighters: A narrative review 消防队员急性和慢性炎症：一个叙述性的回顾。

IF 4.2 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research

Pub Date : 2025-07-01 DOI: 10.1016/j.mrrev.2025.108569

Giselle L. Allsopp , Luana C. Main

In 2022, an International Agency for Research on Cancer (IARC) Monographs Working Group assessed the carcinogenic hazard of occupational exposure as a firefighter. The working group concluded that occupational exposure as a firefighter is carcinogenic to humans and identified chronic inflammation as a contributing factor. This review therefore aimed to summarise the evidence of acute and chronic inflammation in firefighters. Acute and chronic (>2–6 weeks) levels inflammatory markers (Eg. Interleukin (IL) 1β, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNFα), C reactive protein (CRP)) were examined in firefighters following exposure to typical firefighting duties including structural and wildland fires. Experimental studies without exposure to combustion emissions were also reviewed to examine the specific contribution of heat exposure, physical exertion, cognitive load and restricted sleep to inflammation in firefighters. For chronic inflammation, the strongest evidence existed for elevated circulating IL-6 (n = 5 studies), followed by elevated IL-1β (n = 3), CRP (n = 3) and IL-8 (n = 2). Acute elevations in IL-6 (n = 8 studies), IL-8 (n = 7) and IL-1β (n=4) were also evident in firefighters in the hours and days following exposure to structural and wildland fires. Experimental studies provided evidence that physical exercise and heat contribute to acute elevations in IL-6 (n = 6) and TNFα (n = 3). In summary, the data reviewed provide strong support that typical firefighting duties can induce both acute and chronic inflammation. More work is needed to determine the prevalence of inflammation in firefighters and to identify mitigating strategies to lower the risk of firefighters developing inflammatory related-chronic disease.

2022年，国际癌症研究机构（IARC）专著工作组评估了消防员职业暴露的致癌危害。该工作组得出结论，消防员的职业暴露对人类是致癌的，并确定慢性炎症是一个促成因素。因此，本综述旨在总结消防员急性和慢性炎症的证据。急性和慢性（bb0 2-6周）至少42种炎症标志物的水平(如：在暴露于典型的消防任务（包括结构火灾和野火）后，对消防员的白细胞介素（IL） 1β、IL-6、IL-8、IL-10、肿瘤坏死因子α (TNFα)、C反应蛋白（CRP）进行了检测。研究人员还回顾了没有暴露于燃烧排放物的实验研究，以检查热暴露、体力消耗、认知负荷和睡眠不足对消防员炎症的具体影响。对于慢性炎症，最有力的证据是循环IL-6升高（n=5项研究），其次是IL-1β (n=3)、CRP （n=3）和IL-8 （n=2）升高。IL-6 （n=8项研究）、IL-8 （n=7项研究）和IL-1β（4项研究）在暴露于结构性火灾和野火后的数小时和数天内也明显升高。实验研究证明，体育锻炼和热量有助于IL-6 （n=6）和tnf - α (n=3)的急性升高。总之，回顾的数据提供了强有力的支持，即典型的消防工作可以诱发急性和慢性炎症。需要做更多的工作来确定消防员中炎症的患病率，并确定减轻策略以降低消防员患炎症相关慢性疾病的风险。

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引用次数: 0