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Piezo1 activation in endothelial cells aggravates microvascular ischemia–reperfusion injury in limbs by enhancing ferroptosis 内皮细胞中的Piezo1激活通过增强铁下垂加重肢体微血管缺血-再灌注损伤。
IF 12.9 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-09 DOI: 10.1038/s12276-025-01616-9
Fan-feng Chen, Yin-he Zhang, Zi-chang Wu, Kaiyi Du, Xinyuan Chen, Yang Lu, Qianqian Hu, Anyu Du, Shenghu Du, Jian Wang, Keqing Shi, Zimiao Chen, Zili He, Kailiang Zhou, Jian Xiao
Acute limb ischemia–reperfusion injury (ALIRI) prominently involves microvascular dysfunction, with notable contributions from damage to microvascular endothelial cells (MECs). Previous research suggests that the mechanosensitive ion channel Piezo1 becomes active in response to mechanical stress conditions, including ischemia and trauma. However, its precise function within the ALIRI context remains elusive. Notably, the expression of Piezo1 was markedly elevated postreperfusion in mouse hind limb ischemia/reperfusion (I/R) models, implicating its crucial involvement in limb survival. Employing specific inhibitors of cell death pathways, the study delineated key molecular drivers of ferroptosis during limb damage. Here evaluations of limb vitality, western blot, quantitative PCR and immunofluorescence implicated that activation of Piezo1 by its agonist exacerbates I/R-induced microvascular perfusion deficits, tissue swelling, skeletal muscle damage and increased tissue infarction and MECs damage. Conversely, these detrimental impacts were mitigated through pharmacological blockade of Piezo1 or specific deletion of Piezo1 in MECs. Comprehensive untargeted metabolomic analysis revealed significant changes primarily in glycerophospholipid and arachidonic acid metabolism pathways. Further experiments demonstrated that RNA interference-mediated inhibition of cytosolic phospholipase A2 (cPLA2) and acyl-CoA synthetase long-chain family member 4 (ACSL4) negated the protective effects against ferroptosis and limb damage that were observed with Piezo1 deletion. Moreover, this study confirmed that protein kinase C phosphorylates ACSL4, which mediates Piezo1-induced ferroptosis and exacerbates limb damage, as shown through immunoprecipitation studies. In summary, Piezo1 contributes to the exacerbation of microvascular and skeletal muscle damage in ALIRI by facilitating the cPLA2-dependent release of arachidonic acid and promoting ACSL4-driven lipid peroxidation, thereby intensifying ferroptosis in MECs. Acute limb ischemia–reperfusion injury (ALIRI) is a serious condition that can occur after blood flow is restored to a limb. This can cause damage to small blood vessels and tissues. Here researchers wanted to understand how a protein called Piezo1 affects this process. The researchers created a model of ALIRI in mice and observed the effects of Piezo1 on cell death and tissue damage. They found that Piezo1 activation increases calcium levels in cells, which then triggers a series of reactions leading to cell death through a process called ferroptosis. They also discovered that inhibiting Piezo1 reduced tissue damage and cell death. The study concludes that targeting Piezo1 could be a potential strategy to prevent tissue damage in ALIRI. Future research may focus on developing treatments that inhibit Piezo1 to improve outcomes for patients with this condition. This summary was initially drafted using artificial intelligence, then revised and fact-checked by t
急性肢体缺血再灌注损伤(ALIRI)主要涉及微血管功能障碍,其中微血管内皮细胞(MECs)损伤最为显著。先前的研究表明,机械敏感离子通道Piezo1在机械应力条件下变得活跃,包括缺血和创伤。然而,它在ALIRI环境中的确切功能仍然难以捉摸。值得注意的是,在小鼠后肢缺血/再灌注(I/R)模型中,Piezo1的表达在灌注后显著升高,暗示其在肢体存活中起重要作用。利用细胞死亡途径的特异性抑制剂,该研究描绘了肢体损伤期间铁下垂的关键分子驱动因素。本研究对肢体活力、western blot、定量PCR和免疫荧光的评估表明,Piezo1的激动剂激活会加剧I/ r诱导的微血管灌注缺陷、组织肿胀、骨骼肌损伤以及组织梗死和mec损伤的增加。相反,通过药理阻断Piezo1或在mec中特异性删除Piezo1,可以减轻这些有害影响。全面的非靶向代谢组学分析显示,甘油磷脂和花生四烯酸代谢途径主要发生了显著变化。进一步的实验表明,RNA干扰介导的胞质磷脂酶A2 (cPLA2)和酰基辅酶a合成酶长链家族成员4 (ACSL4)的抑制否定了Piezo1缺失所观察到的对铁ptosis和肢体损伤的保护作用。此外,本研究通过免疫沉淀研究证实,蛋白激酶C磷酸化ACSL4, ACSL4介导piezo1诱导的铁上吊并加重肢体损伤。综上所述,Piezo1通过促进cpla2依赖性花生四烯酸的释放,促进acsl4驱动的脂质过氧化,从而加剧了ALIRI中微血管和骨骼肌的损伤,从而加剧了MECs中的铁凋亡。
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引用次数: 0
Threonic acid, an ascorbic acid metabolite, synergizes with intermittent fasting to ameliorate obesity 苏氨酸,一种抗坏血酸代谢物,与间歇性禁食协同作用,改善肥胖。
IF 12.9 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-09 DOI: 10.1038/s12276-025-01613-y
Sungjoon Oh, Seokjae Park, Eun-Kyoung Kim
Intermittent fasting (IF) is a safe and sustainable approach for obesity treatment, yet its weight loss efficacy is relatively modest compared with that of pharmacologic anti-obesity therapies. The synergistic benefits of pairing IF with administration of nutrient-derived metabolites remain poorly understood. Here we report that combining IF with threonic acid (TA), an ascorbic acid metabolite, led to more pronounced reductions in body weight and food intake, as well as improvements in energy expenditure and glycemic control, compared with either intervention alone in diet-induced obese mice. These metabolic benefits were associated with the anorexigenic role of TA in reversing fasting-induced upregulation of the hypothalamic orexigenic neuropeptides NPY and AGRP. In the hypothalamus, TA competed with glucose for uptake via glucose transporter 3 (GLUT3), while IF boosted the TA uptake through both glucose depletion and upregulation of GLUT3, resulting in a more robust suppression of NPY and AGRP expression. Collectively, our findings highlight the combination of TA with IF as a promising metabolite-based combinatorial strategy to enhance the therapeutic efficacy of obesity treatment. Obesity is a growing health issue worldwide. Current treatments have side effects and limited long-term success. This study explores combining intermittent fasting (IF), a dietary approach involving alternating periods of eating and fasting, with either ascorbic acid (AA, also known as vitamin C) or its metabolite, threonic acid (TA), to enhance obesity treatment. In the study, mice were fed a high-fat diet to induce obesity and then subjected to IF and AA or TA treatments. Researchers found that IF combined with TA was more effective than IF with AA or either treatment alone in reducing body weight and improving metabolic health. These metabolic benefits were associated with TA’s appetite-suppressing action in reversing fasting-induced increases in hypothalamic orexigenic neuropeptides. The study concludes that TA could be a promising strategy for treating obesity. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
间歇性禁食(IF)是一种安全且可持续的肥胖治疗方法,但与药物抗肥胖治疗相比,其减肥效果相对温和。配对IF与营养衍生代谢物管理的协同效益仍然知之甚少。在这里,我们报告说,与单独干预相比,在饮食诱导的肥胖小鼠中,IF与苏酸(一种抗坏血酸代谢物)联合使用,导致体重和食物摄入量的显著减少,以及能量消耗和血糖控制的改善。这些代谢益处与TA在逆转空腹诱导的下丘脑促氧神经肽NPY和AGRP上调中的厌氧作用有关。在下丘脑中,TA通过葡萄糖转运体3 (GLUT3)与葡萄糖竞争摄取,而IF通过葡萄糖消耗和GLUT3的上调促进TA的摄取,从而更强烈地抑制NPY和AGRP的表达。总的来说,我们的研究结果强调了TA与IF的联合作为一种有希望的基于代谢物的组合策略来提高肥胖治疗的疗效。
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引用次数: 0
The functional imperative in high-grade glioma 高级别胶质瘤的功能要求。
IF 12.9 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-08 DOI: 10.1038/s12276-025-01614-x
Laura Shih Hui Goh, Dexter Kai Hao Thng, Yvonne Li En Ang, Dean Ho, Tan Boon Toh, Andrea Li Ann Wong
Precision oncology has emerged as a promising strategy for treating high-grade gliomas, yet its clinical impact has been disappointing, with over 300 clinical trials on targeted therapies failing to yield substantial improvements in patient outcomes. Current approaches primarily focus on static, marker-driven tumor features, which capture only a small portion of the complex biology that governs therapeutic responses. Functional precision oncology (FPO) offers a complementary approach, enhancing treatment selection in a personalized manner by dynamically testing patient-derived tumor cells against a range of available therapeutic agents. Here this review examines both historical and contemporary treatment strategies for high-grade gliomas and explores underlying reasons for the limited success of multiple precision oncology initiatives. We demonstrate how the incorporation of FPO in the armamentarium of glioma therapies may address these challenges and outline its proposed role as well as the practical considerations in utilizing FPO for clinical decision-making in patients with glioma. Precision oncology aims to tailor cancer treatments based on individual genetic profiles. This study highlights the challenges faced in using genomic data alone to predict treatment outcomes for high-grade gliomas. The researchers discuss the emergence of functional precision oncology (FPO) as a promising strategy. FPO involves testing a patient’s tumor cells directly against various drugs to identify effective treatments. This method considers the complex biology of tumors, which genomic data alone may not capture. In their study, the authors addresses the use of patient-derived models, such as organoids (3D cell cultures), to test drug responses. These models help identify personalized treatment options by simulating how tumors react to different therapies. The study concludes that FPO can complement genomic approaches, offering a more comprehensive understanding of tumor behavior and improving treatment strategies for high-grade gliomas. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
精准肿瘤学已成为治疗高级别胶质瘤的一种有前景的策略,但其临床效果令人失望,超过300项针对靶向治疗的临床试验未能显著改善患者的预后。目前的方法主要集中在静态的、标记驱动的肿瘤特征上,这些特征只捕获了控制治疗反应的一小部分复杂生物学。功能精确肿瘤学(FPO)提供了一种补充方法,通过动态测试患者来源的肿瘤细胞对一系列可用治疗剂的影响,以个性化的方式增强治疗选择。本文回顾了高级别胶质瘤的历史和现代治疗策略,并探讨了多种精确肿瘤学计划有限成功的潜在原因。我们展示了FPO在胶质瘤治疗方案中的应用如何解决这些挑战,并概述了FPO在胶质瘤患者临床决策中所发挥的作用以及实际考虑因素。
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引用次数: 0
Revisiting noncoding RNAs: emerging coding functions and their impact on skeletal muscle development 重新审视非编码rna:新兴的编码功能及其对骨骼肌发育的影响。
IF 12.9 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-08 DOI: 10.1038/s12276-025-01610-1
Dandan Zhong, Jian Wang, Qi Li, Chuang Wang, Yuanyuan Huang, Yanhong Cao, Hui Li
Accumulating evidence has revealed noncoding RNAs (ncRNAs) as versatile regulators in skeletal muscle development, extending beyond their canonical roles as nontranslating transcripts. Recent advancements in proteomics and translatomics have demonstrated that ncRNAs containing cryptic open reading frames can encode peptides/proteins. Here we systematically evaluate computational tools and databases for predicting ncRNA-encoded products, dissect the molecular mechanisms underlying their translation and synthesize the current landscape of ncRNA-derived peptides/proteins identified in skeletal muscle across species. We further discuss their emerging roles in myogenesis and potential clinical implications for muscle-related disorders. By highlighting the dual functionality of ncRNAs as both regulatory RNAs and peptide/protein precursors, this work provides a comprehensive resource for understanding the expanding complexity of skeletal muscle development and proposes novel therapeutic targets for muscle diseases. The study explores the role of noncoding RNAs (ncRNAs) in muscle development and disease. Here, we address the gap in understanding how these ncRNA-encoded peptides function in muscle biology. Researchers reviewed methods to predict and validate the protein-coding potential of ncRNAs. They used bioinformatics tools to identify small open reading frames within ncRNAs, which are sequences that can potentially code for proteins. Techniques such as ribosome profiling (Ribo-seq) and mass spectrometry were employed to confirm the presence of these peptides. The findings reveal that ncRNA-encoded peptides play crucial roles in muscle development and may offer new therapeutic targets for muscle diseases. For instance, some peptides regulate calcium transport in muscle cells, affecting contraction and growth. The study concludes that understanding ncRNA-encoded peptides could lead to novel treatments for muscle disorders. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
越来越多的证据表明,非编码rna (ncRNAs)在骨骼肌发育中是多功能的调节因子,超出了它们作为非翻译转录物的典型作用。蛋白质组学和翻译组学的最新进展表明,含有隐式开放阅读框的ncrna可以编码肽/蛋白质。在这里,我们系统地评估了用于预测ncrna编码产物的计算工具和数据库,剖析了它们翻译的分子机制,并合成了在不同物种的骨骼肌中鉴定的ncrna衍生肽/蛋白的现状。我们进一步讨论了它们在肌肉发生中的新作用以及对肌肉相关疾病的潜在临床意义。通过强调ncRNAs作为调控rna和肽/蛋白前体的双重功能,这项工作为理解骨骼肌发育日益复杂的过程提供了全面的资源,并为肌肉疾病提出了新的治疗靶点。
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引用次数: 0
Multilayered regulation of cytoskeletal protein abundance: autoregulatory mechanisms of actin and tubulin 细胞骨架蛋白丰度的多层调节:肌动蛋白和微管蛋白的自调节机制。
IF 12.9 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-08 DOI: 10.1038/s12276-025-01615-w
Yena Cho, Yong Kee Kim
Structural proteins such as actin and tubulin form the fundamental framework of the cytoskeleton and are essential for diverse cellular processes, including morphogenesis, intracellular transport and cell division. Maintaining precise intracellular levels is crucial for cellular homeostasis because both excess and deficiency can lead to cytotoxicity. Although transcriptional regulation establishes basal expression levels, recent studies have highlighted the crucial role of post-transcriptional and post-translational mechanisms in the fine-tuning of cytoskeletal protein abundance in response to dynamic cellular demands. Actin and tubulin use distinct autoregulatory strategies. Tubulin mRNA undergoes cotranslational decay, mediated by TTC5 and tightly regulated by the CARM1–PI3KC2α axis, linking ribosome-associated quality control with post-translational modifications. Conversely, actin regulation involves mRNA localization via ZBP1 and spatially restricted translation, coupled with a G-actin–MRTF/SRF transcriptional feedback loop. In addition, the ubiquitin–proteasome system modulates cytoskeletal protein turnover and fine-tunes microtubule dynamics. The dysregulation of these pathways has been implicated in various human diseases, including tubulinopathies, cancer and myopathies. In this Review, we summarize the multilayered regulatory networks that control actin and tubulin abundance, highlight recent advances in autoregulatory circuits and their disease relevance, and discuss future research directions for the therapeutic targeting of cytoskeletal proteostasis. Mammalian cells rely on structures called the cytoskeleton, which includes actin filaments and microtubules, to maintain their shape and function. This study explores how cells regulate the levels of actin and tubulin, the building blocks of these structures. When these proteins are not balanced, it can lead to cell damage. The authors review how cells control these proteins through various mechanisms. The study highlights that cells use transcriptional regulation and post-transcriptional mechanisms to manage protein levels. For example, when there is too much free tubulin, a feedback loop reduces its production by degrading its mRNA. Similarly, actin levels are controlled by feedback mechanisms that adjust mRNA stability based on the amount of unpolymerized actin. The findings emphasize the importance of these regulatory systems in maintaining cellular health. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
结构蛋白如肌动蛋白和微管蛋白构成细胞骨架的基本框架,对多种细胞过程至关重要,包括形态发生、细胞内运输和细胞分裂。维持精确的细胞内水平对细胞稳态至关重要,因为过量和缺乏都会导致细胞毒性。虽然转录调控建立了基础表达水平,但最近的研究强调了转录后和翻译后机制在细胞骨架蛋白丰度的微调中发挥的关键作用,以响应动态细胞需求。肌动蛋白和微管蛋白使用不同的自动调节策略。微管蛋白mRNA经历共翻译衰变,由TTC5介导,并受到CARM1-PI3KC2α轴的严格调控,将核糖体相关的质量控制与翻译后修饰联系起来。相反,肌动蛋白调节涉及通过ZBP1定位mRNA和空间受限翻译,以及G-actin-MRTF/SRF转录反馈回路。此外,泛素-蛋白酶体系统调节细胞骨架蛋白周转和微调微管动力学。这些通路的失调与各种人类疾病有关,包括小管蛋白病、癌症和肌病。在本文中,我们总结了控制肌动蛋白和微管蛋白丰度的多层调节网络,重点介绍了自调节回路及其疾病相关性的最新进展,并讨论了未来治疗靶向细胞骨架蛋白停滞的研究方向。
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引用次数: 0
Colorectal microenvironment determines the prognosis of colorectal cancer 结直肠微环境决定结直肠癌的预后。
IF 12.9 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-07 DOI: 10.1038/s12276-025-01599-7
Yeong Hak Bang, Ji Hye Choi, Kyunghee Park, Boram Lee, Kyung Yeon Han, Dae Hee Pyo, Yong Beom Cho, Tae-You Kim, Kyu Joo Park, Seung-Bum Ryoo, Sung-Bum Kang, Chang Sik Yu, Jaeim Lee, Kil-yong Lee, Kyu-Tae Kim, Jin-Young Lee, Hoang Bao Khanh Chu, Nameeta Shah, Shashank Gupta, Pranali Sonpatki, Young-Joon Kim, Woong-Yang Park
Here we aimed to evaluate the feasibility of distinguishing colorectal microenvironments that support cancer cell growth from those that do not. We hypothesized that patients whose non-tumor-bearing tissue (NBT) obtained from the furthest margins of resected cancer specimens resembled the tumor had a poorer prognosis. Patients with colorectal cancer were divided into groups with tumor-supportive (TSM) or healthy microenvironments using bulk RNA sequencing data from 273 paired NBT and tumor samples. Patients in the TSM group exhibited significantly poorer 5-year recurrence-free survival and overall survival compared with those in the healthy microenvironment group. Pathway and 16S rRNA sequencing analyses revealed that NBT and tumors from the TSM group shared a microbiome composition, along with decreased pathway activity related to microvilli maintenance and flavonoid or vitamin metabolic processes. Single-cell RNA sequencing uncovered upregulated interactions between IL1Bhigh neutrophils and OLFM4+ epithelial cells in NBTs from the TSM group, as well as organized microniches in TSM tumors, featuring interactions between EMP1high epithelial cells, IL1Bhigh neutrophils and GZMKhigh CD8+ T cells. Collectively, the colorectal microenvironment can serve as a prognostic biomarker to effectively predict cancer invasiveness and tumor-promoting inflammation. Maintaining a healthy colorectal mucosal microenvironment, potentially through dietary intervention, is crucial. Colorectal cancer (CRC) is a complex disease with varied genetic and environmental factors. Current genomic markers help to predict treatment outcomes for advanced cases but not for early-stage CRC. About 30–40% of CRC cases return after surgery, indicating a need for better predictive tools. Researchers explored using normal-looking tissue near tumors as a potential marker for recurrence. This study involved 273 patients with stage II or III CRC who underwent surgery. Researchers used RNA sequencing to analyze both the tumor and the nearby normal tissues. They identified specific genes that were more active in tumors and used these to classify patients into two groups: those with a tumor-supportive environment and those with a healthier environment. The results showed that patients with tumor-like features in their normal tissue had worse survival rates. This suggests that the surrounding tissue’s condition can predict cancer recurrence. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
在这里,我们旨在评估区分支持癌细胞生长和不支持癌细胞生长的结直肠微环境的可行性。我们假设,从切除肿瘤标本的最远边缘获得的非瘤组织(NBT)与肿瘤相似的患者预后较差。使用来自273对NBT和肿瘤样本的大量RNA测序数据,将结直肠癌患者分为肿瘤支持(TSM)组或健康微环境组。与健康微环境组相比,TSM组患者的5年无复发生存率和总生存率明显较差。通路和16S rRNA测序分析显示,来自TSM组的NBT和肿瘤具有相同的微生物组组成,以及与微绒毛维持和类黄酮或维生素代谢过程相关的通路活性降低。单细胞RNA测序揭示了TSM组nbt中IL1Bhigh中性粒细胞和OLFM4+上皮细胞之间的相互作用上调,以及TSM肿瘤中有组织的微细胞,主要表现为EMP1high上皮细胞、IL1Bhigh中性粒细胞和GZMKhigh CD8+ T细胞之间的相互作用。综上所述,结直肠微环境可以作为一种预后生物标志物,有效预测癌症侵袭性和促肿瘤炎症。维持健康的结肠黏膜微环境,可能通过饮食干预,是至关重要的。
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引用次数: 0
Roles of cytoskeleton in metastasis: from its mechanism to therapeutic strategies 细胞骨架在转移中的作用:从其机制到治疗策略。
IF 12.9 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-07 DOI: 10.1038/s12276-025-01608-9
Seyeon Lim, Soyeon Woo, Ki Won Lee, Kwang Dong Kim
The cytoskeleton is a dynamic intracellular protein network composed of actin filaments, microtubules and intermediate filaments that provides structural support in cells and plays a crucial role in tumor metastasis. Tumor cells encounter various dynamic mechanical environments during metastasis, and they adapt to these environments through cytoskeletal reorganization, which enables them to regulate cell morphology, generate intracellular forces and induce intracellular signaling. Actin filaments contribute to migration and extracellular matrix degradation by forming protrusive structures, such as lamellipodia, filopodia and invadopodia. Microtubules support migration, stabilize cell polarity and enhance survival under shear stress. Intermediate filaments maintain structural integrity and mechanical flexibility, allowing cancer cells to pass through narrow spaces. The cytoskeleton’s pivotal role in regulating metastasis makes it a promising drug target. However, cytoskeleton-targeting drugs often face the challenges of nonspecificity and drug resistance. Recent advancements in the field have tried to overcome these limitations through selective targeting, drug delivery systems, antibody–drug conjugates and combination therapies. Here we summarize the roles and regulatory mechanisms of the cytoskeleton in metastasis and discusse the current cytoskeleton-targeting therapies, including their mechanisms, clinical applications and limitations. Furthermore, this review suggests future directions for developing effective and safe cytoskeleton-based interventions against metastasis. Cancer spread, or metastasis, is a major challenge in treating cancer and often leads to death. This process involves cancer cells changing shape and moving through the body. The cytoskeleton, microtubules and intermediate filaments, helps cancer cells move and survive. Researchers have found that targeting the cytoskeleton could help stop cancer spread. However, drugs that target the cytoskeleton can also harm normal cells, causing side effects. Researchers reviewed how the cytoskeleton helps cancer cells spread and discussed current drugs targeting it. They highlighted issues with these drugs, such as toxicity and resistance. The study also explored new strategies to improve these treatments, combining them with other drugs or using advanced delivery systems such as nanoparticles. Researchers concluded that although targeting the cytoskeleton shows promise, more work is needed to make these treatments safer and more effective. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
细胞骨架是由肌动蛋白丝、微管和中间丝组成的细胞内动态蛋白网络,在细胞内提供结构支持,在肿瘤转移中起着至关重要的作用。肿瘤细胞在转移过程中会遇到各种动态机械环境,它们通过细胞骨架重组来适应这些环境,从而调节细胞形态,产生细胞内力,诱导细胞内信号传导。肌动蛋白丝通过形成突出的结构,如板足、丝状足和侵入足,促进迁移和细胞外基质降解。微管支持迁移,稳定细胞极性,增强剪切应力下的存活。中间细丝保持结构完整性和机械灵活性,允许癌细胞通过狭窄的空间。细胞骨架在调节转移中的关键作用使其成为一个有希望的药物靶点。然而,细胞骨架靶向药物经常面临非特异性和耐药的挑战。该领域的最新进展试图通过选择性靶向、药物传递系统、抗体-药物偶联物和联合疗法来克服这些限制。本文综述了细胞骨架在肿瘤转移中的作用和调控机制,并对目前细胞骨架靶向治疗的机制、临床应用及局限性进行了讨论。此外,本文还提出了未来发展有效和安全的基于细胞骨架的转移干预措施的方向。
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引用次数: 0
Photooxidative molecular damage under blue light 蓝光下的光氧化分子损伤。
IF 12.9 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-07 DOI: 10.1038/s12276-025-01609-8
Eojin Kim, Seoyoon Kim, Minseung Kim, Duyoung Min
The widespread adoption of artificial lighting has substantially increased human exposure to blue light across various environments, raising concerns about its potential adverse effects on human health. Over the past decades, blue light-induced biological responses have been investigated across multiple levels—from mechanistic studies of photoinduced reactive oxygen species generation to broader physiological consequences. Since all cellular and tissue-level effects ultimately originate from structural and functional alterations in molecular components, a comprehensive understanding of blue light-induced molecular damage is clearly warranted. This review summarizes current knowledge and recent findings on photooxidative molecular damage induced by blue light exposure, with a focus on the primary photochemical mechanisms of reactive oxygen species generation, blue light-sensitive endogenous photosensitizers, and the resulting oxidative damage to key biomolecules, including proteins, DNA and lipids. These insights collectively establish a more integrated framework for understanding how blue light compromises molecular integrity within cells. Sunlight is essential for life on Earth, comprising ultraviolet (UV), visible and infrared radiation. While the harmful effects of UV on the skin and eyes are well established, recent attention has turned to blue light—the high-energy portion of visible light—which is abundant in sunlight and also commonly emitted by digital screens and LED lighting. Experimental studies in human cells and animal models have shown that excessive blue light exposure can generate reactive oxygen species, leading to oxidative damage of DNA, proteins and lipids. Such molecular damage may contribute to skin photoaging and has been implicated as a potential factor in retinal disorders, including age-related macular degeneration. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
人工照明的广泛采用大大增加了人类在各种环境中接触蓝光的机会,引起了人们对其对人类健康的潜在不利影响的关注。在过去的几十年里,蓝光诱导的生物反应已经在多个层面上进行了研究——从光诱导活性氧产生的机制研究到更广泛的生理后果。由于所有细胞和组织水平的影响最终源于分子成分的结构和功能改变,因此对蓝光诱导的分子损伤的全面理解显然是有必要的。本文综述了蓝光照射引起的光氧化分子损伤的现有知识和最新发现,重点介绍了活性氧产生的主要光化学机制、蓝光敏感的内源性光敏剂以及对关键生物分子(包括蛋白质、DNA和脂质)的氧化损伤。这些见解共同建立了一个更完整的框架,以了解蓝光如何损害细胞内的分子完整性。
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引用次数: 0
Author Correction: Methyl-CpG-binding domain 2 mitigates osteoarthritis through Steap3 promoter methylation and chondrocyte ferroptosis regulation 作者更正:甲基- cpg结合结构域2通过Steap3启动子甲基化和软骨细胞铁下垂调节减轻骨关节炎。
IF 12.9 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-06 DOI: 10.1038/s12276-025-01620-z
Renpeng Peng, Meng Zheng, Honglei Kang, Yimin Dong, Pengju Wang, Congyi Wang, Jun Xiao, Feng Li, Xuying Sun
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引用次数: 0
Somatic mutations and clonal evolution in normal tissues and cancer development. 正常组织的体细胞突变和克隆进化与癌症的发生。
IF 12.9 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-12-02 DOI: 10.1038/s12276-025-01592-0
Kenichi Yoshida

Understanding the early stages of carcinogenesis requires detailed insight into the abnormalities present in normal cells before cancer onset. In the past, it was difficult to analyze genomic abnormalities in small clones in normal tissues. However, recent technological advances in genomic analysis have shed light on the process of accumulation of somatic mutations in normal cells, which is driven by factors such as aging and environmental influences. Even in normal tissues, clones that have acquired driver mutations-either directly contributing to carcinogenesis or adapting to specific pathological or genetic backgrounds-are frequently selected, leading to clonal expansion. Normal cells undergo clonal evolution into cancer cells over several decades, with the initial acquisition of a driver mutation occurring in early life. Here this review presents recent findings concerning the accumulation of somatic mutations in normal cells, acquisition of driver mutations and clonal evolution toward cancer.

了解癌变的早期阶段需要详细了解癌变发生前正常细胞中的异常情况。过去,很难分析正常组织中小克隆的基因组异常。然而,最近基因组分析的技术进步揭示了正常细胞中体细胞突变积累的过程,这是由衰老和环境影响等因素驱动的。即使在正常组织中,获得驱动突变的克隆——要么直接导致致癌,要么适应特定的病理或遗传背景——经常被选择,导致克隆扩增。正常细胞经过几十年的克隆进化成癌细胞,最初获得的驱动突变发生在生命早期。本文综述了正常细胞中体细胞突变的积累、驱动突变的获得和向癌症的克隆进化的最新发现。
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Experimental and Molecular Medicine
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