Molecular Aspects of Medicine最新文献_第3页

Pharmacological reprogramming of plitidepsin as a SARS-CoV-2 inhibitor 多重抑郁素作为SARS-CoV-2抑制剂的药理学重编程

IF 10.3 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-12-01 Epub Date: 2025-11-10 DOI: 10.1016/j.mam.2025.101412

Jose Jimeno , Jose Felipe Varona , Jose A. Lopez-Martin , Nuria Izquierdo-Useros , Elisa Molina Molina , Pablo Guisado-Vasco , Martin Sachse , Cristina Risco , Alejandro Losada , Salvador Fudio , Erik Luepke , Antonio Nieto , Javier Gomez , Pablo Aviles , Carmen Cuevas , Mehdi Bouhaddou , Isabel Sola , Nevan J. Krogan , Luis Enjuanes , Jose M. Fernandez-Sousa , Kris White

Selective pressures in the ocean promote the evolution of potent molecules that may be useful in therapeutic settings. Tunicates provide a rich source of bioactive molecules that have been shown to have anti-neoplastic and anti-microbial activities. Plitidepsin, a natural marine cyclic depsipeptide originally isolated from the tunicate Aplidium albicans, was originally developed as an anti-tumor drug, and has been approved for use in Australia in patients with advanced pretreated myeloma. Early in the SARS-CoV-2 pandemic, plitidepsin was shown to have potent preclinical efficacy against the virus, suggesting that it could be repurposed for the treatment of COVID-19. This review summarizes the clinical development of plitidepsin first as an anti-tumor drug, before providing a recapitulation of current efforts to repurpose the molecule as an antiviral therapy. The pharmacokinetic and pharmacodynamic data on plitidepsin will be analyzed, and the various experimental lines of evidence in support of the molecule's multifactorial mechanism of action will be explored. Finally, the available data on the use of plitidepsin in patients with COVID-19 will be presented, including results from a Phase I proof-of-concept study, real-world data from immunocompromised patients, and a look of results from a Phase III clinical trial that confirms the working hypothesis.

海洋中的选择性压力促进了可能在治疗环境中有用的强效分子的进化。被囊动物提供了丰富的生物活性分子来源，这些活性分子已被证明具有抗肿瘤和抗微生物活性。Plitidepsin是一种天然的海洋环状沉积肽，最初是从被膜状白单胞菌中分离出来的，最初是作为抗肿瘤药物开发的，并已被批准在澳大利亚用于晚期预处理骨髓瘤患者。在SARS-CoV-2大流行的早期，plitidepsin被证明对该病毒具有强大的临床前疗效，这表明它可以被重新用于治疗COVID-19。本综述首先总结了plitidepsin作为抗肿瘤药物的临床发展，然后概述了目前将该分子重新用作抗病毒治疗的努力。将分析plitidepsin的药代动力学和药效学数据，并探索支持该分子多因子作用机制的各种实验证据。最后，将介绍关于在COVID-19患者中使用plitidepsin的现有数据，包括I期概念验证研究的结果、免疫功能低下患者的真实数据，以及证实工作假设的III期临床试验的结果。

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引用次数: 0

Multidimensional review of viral infectious ocular diseases: Post-Pandemic epidemiology and future directions for control 病毒性感染性眼病的多维回顾：大流行后流行病学和未来控制方向。

IF 10.3 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-12-01 Epub Date: 2025-11-24 DOI: 10.1016/j.mam.2025.101428

Chang Liu , Qianhao Yang , Yang Shen , Mengqiao Xu

Viral Infectious Ocular Diseases (VIODs) remain a major global cause of vision loss, ranging from highly transmissible conjunctivitis to blinding keratitis and complex neuro-ophthalmic syndromes. Furthermore, the Coronavirus Disease 2019 (COVID-19) pandemic and subsequent reported ocular diseases have fundamentally changed the landscape of VIOD epidemiology and management. Epidemiological data indicate heterogeneous effects on common infections such as Adenoviral conjunctivitis due to varying compliance with hygiene measures. Concurrently, systemic immunological events, notably those induced by COVID-19 infection or certain vaccinations, have been linked to the reactivation of latent Alphaherpesviruses, including Herpes Simplex Virus (HSV) and Varicella Zoster Virus (VZV).

The metagenomic next-generation sequencing (mNGS) offers a significantly improved diagnostic yield (up to 92.7 % in some cohorts) for complex infectious keratitis compared to conventional methods, providing an unbiased tool crucial for timely, targeted treatment. Therapeutic challenges are defined by the persistent threat of antiviral resistance, primarily driven by mutations in the viral Thymidine Kinase (TK) gene. To overcome poor ocular bioavailability, novel drug delivery systems (NDDS), such as Acyclovir-loaded Niosomes and Cubosomes, show promise by enabling sustained drug release and enhanced corneal permeation. Effective future VIOD control requires a multi-pronged strategy integrating robust global surveillance, rapid deployment of advanced molecular diagnostics, and the clinical implementation of resistance-beating therapies delivered via optimized nanocarrier platforms.

This review provides the current understanding of VIODs, focusing on the epidemiological shifts observed post-2020, advancements in molecular diagnostics, challenges posed by antiviral resistance, and the emergence of next-generation therapeutic strategies.

病毒性感染性眼病（VIODs）仍然是全球视力丧失的主要原因，从高度传染性结膜炎到致盲性角膜炎和复杂的神经-眼科综合征。此外，2019冠状病毒病（COVID-19）大流行和随后报告的眼部疾病从根本上改变了视频病流行病学和管理的格局。流行病学数据表明，由于对卫生措施的不同遵守，对腺病毒结膜炎等常见感染的影响不尽相同。同时，系统性免疫事件，特别是由COVID-19感染或某些疫苗接种引起的免疫事件，与潜伏的甲型疱疹病毒（包括单纯疱疹病毒（HSV）和水痘带状疱疹病毒（VZV））的再激活有关。与传统方法相比，新一代宏基因组测序（mNGS）显著提高了复杂感染性角膜炎的诊断率（在某些队列中高达92.7%），为及时、有针对性的治疗提供了一种公正的工具。治疗挑战的定义是抗病毒药物耐药性的持续威胁，主要由病毒胸苷激酶（TK）基因突变驱动。为了克服眼部生物利用度差的问题，新型药物递送系统（NDDS），如载无环鸟苷体和立方体体，通过实现药物持续释放和增强角膜渗透显示出希望。未来有效的VIOD控制需要多管齐下的策略，包括强大的全球监测，先进分子诊断的快速部署，以及通过优化的纳米载体平台提供的抗药治疗的临床实施。本文综述了目前对VIODs的认识，重点介绍了2020年后观察到的流行病学变化、分子诊断的进展、抗病毒药物耐药性带来的挑战以及下一代治疗策略的出现。

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引用次数: 0

The double-edged sword: How SARS-CoV-2 might fuel lung cancer: Investigating the potential oncogenic mechanisms of the novel coronavirus in lung carcinogenesis 双刃剑：SARS-CoV-2如何引发肺癌：研究新型冠状病毒在肺癌发生中的潜在致癌机制

IF 10.3 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-12-01 Epub Date: 2025-09-26 DOI: 10.1016/j.mam.2025.101413

Wang Shen , Yaohua Guo , Cheng Ai , Xuehai Wang , Gang Li

The COVID-19 pandemic, caused by SARS-CoV-2, has had far-reaching consequences beyond acute respiratory illness, with growing evidence suggesting potential long-term oncogenic effects. Lung cancer, a leading cause of cancer-related mortality, may intersect with COVID-19 through shared molecular pathways and altered disease dynamics. SARS-CoV-2 can exacerbate outcomes in existing cancer patients and potentially contribute to de novo lung carcinogenesis or accelerate progression via chronic inflammation, oxidative stress, immune dysregulation, cellular senescence, cell cycle disruption, metabolic reprogramming, and autophagy impairment. It has been proven that although the SARS virus is not capable of integrating into the host genome, it uses the mechanisms of other human oncoviruses to cause lung cancer. Post-COVID-19 pulmonary fibrosis, observed in up to one-third of severe cases, may act as a tumor precursor bridge through sustained tissue remodeling, extracellular matrix stiffness, and hypoxia-induced epithelial-mesenchymal transition. Epidemiological studies indicate increased cancer-related mortality, metastatic reactivation of dormant cancer cells, and diagnostic delays, shifting presentations toward advanced stages during the pandemic. Synergistic risk factors, including smoking, air pollution, occupational exposures, and genetic predispositions, may further amplify oncogenic potential. The convergence of viral, environmental, and host factors creates a critical need for vigilant surveillance, biomarker development, and preventive strategies. This study aims to synthesize current epidemiological evidence, elucidate the molecular and cellular mechanisms by which SARS-CoV-2 may influence lung carcinogenesis, and highlight clinical implications to guide future research, screening, and therapeutic interventions.

由SARS-CoV-2引起的COVID-19大流行，除了急性呼吸道疾病之外，还产生了深远的影响，越来越多的证据表明其潜在的长期致癌作用。肺癌是癌症相关死亡的主要原因，可能通过共享的分子途径和改变的疾病动态与COVID-19交叉。SARS-CoV-2可加剧现有癌症患者的预后，并可能通过慢性炎症、氧化应激、免疫失调、细胞衰老、细胞周期破坏、代谢重编程和自噬损伤等途径促进新发肺癌的发生或加速进展。已经证明，虽然SARS病毒不能整合到宿主基因组中，但它利用其他人类致癌病毒的机制导致肺癌。在高达三分之一的严重病例中观察到的covid -19后肺纤维化可能通过持续的组织重塑、细胞外基质僵硬和缺氧诱导的上皮-间质转化作为肿瘤前体桥。流行病学研究表明，与癌症相关的死亡率增加，休眠癌细胞的转移性再激活，以及诊断延迟，在大流行期间将症状转移到晚期。协同风险因素，包括吸烟、空气污染、职业暴露和遗传易感性，可能进一步扩大致癌潜力。病毒、环境和宿主因素的融合产生了对警惕监测、生物标志物开发和预防策略的迫切需求。本研究旨在综合现有流行病学证据，阐明SARS-CoV-2可能影响肺癌发生的分子和细胞机制，突出临床意义，指导未来的研究、筛查和治疗干预。

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引用次数: 0

Viruses in gastrointestinal cancers: Molecular pathogenesis, oncogenic mechanisms, and translational perspectives 胃肠道肿瘤中的病毒：分子发病机制、致瘤机制和翻译观点。

IF 10.3 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-12-01 Epub Date: 2025-11-12 DOI: 10.1016/j.mam.2025.101415

Bin Liu , Chengjiang Liu , Caroline Sunggip , GuangJin Pu , Dong Deng

Viral pathogens are one of the most significant causes of human carcinogenesis, contributing to up to 15–20 % of worldwide cancers. The gastrointestinal (GI) tract is one of the most vulnerable human organ system to virus-mediated tumorigenesis as a result of frequent exposure to viral infections and various immunological processes. The present review aims to describe the dual roles of viral infections in the development of gastrointestinal cancers (GICs), with a focus on Human Immunodeficiency Virus (HIV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). HIV represents an oncological challenge in the era of effective antiretroviral therapy (ART), where significant immune dysfunction, persistent inflammation, and gut microbiome disruption render infected patients more susceptible to various GICs. On the other hand, SARS-CoV-2 is an emerging viral pathogen whose potential role in oncogenesis remains controversial yet biologically plausible. In this context, SARS-CoV-2 tropism to the gastrointestinal tissues and its capacity to drive cytokine storms, profound dysbiosis, and immune exhaustion raise significant questions regarding its potential to act as a pro-tumorigenic factor. Discussing mechanistic insights from well-known oncogenic viral pathogens, the present review describes the direct and indirect mechanisms by which these two major viruses may affect GI tumorigenesis. Moreover, this review translates these mechanisms into clinical perspectives, underscoring implications for diagnostics, prevention, and therapeutic strategies, while highlighting urgent research priorities for long-term surveillance and biomarker discovery. It highlights the importance of continuous scientific awareness to address the increasing cancer risks presented by emerging and re-emerging viruses through bridging virology and oncology.

病毒性病原体是人类致癌的最重要原因之一，占全世界癌症病例的15- 20%。由于经常暴露于病毒感染和各种免疫过程，胃肠道是人体最易受病毒介导的肿瘤发生的器官系统之一。本综述旨在描述病毒感染在胃肠道癌症（gic）发展中的双重作用，重点关注人类免疫缺陷病毒（HIV）和严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）。在有效的抗逆转录病毒治疗（ART）时代，HIV代表了一个肿瘤学挑战，在这个时代，显著的免疫功能障碍、持续的炎症和肠道微生物群破坏使感染的患者更容易受到各种gic的影响。另一方面，SARS-CoV-2是一种新兴的病毒病原体，其在肿瘤发生中的潜在作用仍有争议，但生物学上是合理的。在这种情况下，SARS-CoV-2对胃肠道组织的趋向性及其驱动细胞因子风暴、深度生态失调和免疫衰竭的能力，引发了关于其作为促肿瘤因子的潜力的重大问题。讨论了从已知的致癌病毒病原体的机制见解，本文综述了这两种主要病毒可能影响胃肠道肿瘤发生的直接和间接机制。此外，本综述将这些机制转化为临床观点，强调了诊断、预防和治疗策略的意义，同时强调了长期监测和生物标志物发现的迫切研究重点。它强调必须不断提高科学意识，通过架起病毒学和肿瘤学的桥梁，应对新出现和再出现的病毒带来的日益增加的癌症风险。

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引用次数: 0

Research advancements on sumoylation in gastrointestinal cancers 胃肠道肿瘤中sumoylation的研究进展

IF 10.3 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-12-01 Epub Date: 2025-09-12 DOI: 10.1016/j.mam.2025.101401

Xiang Li , Rui Ding , Hui Wang , Sijing Chen , Xirui Fan , Yiyao Duan , Jun Hu , Hao Hu , Rui Wu , Rong Qin

SUMOylation is a critical post-translational modification that modulates protein activity, stability, and subcellular distribution through the covalent attachment of SUMO proteins (SUMO1-5) to specific targets. This process is mediated by a cascade of enzymes, including E1, E2, E3 ligases, and deSUMOylation enzymes, enabling precise control over diverse biological functions such as gene expression, cell cycle regulation, DNA damage repair, signaling cascades, and metabolic pathways.

Dysregulation of SUMOylation enzymes has been contributes to cancer initiation, and treatment resistance, by enhancing tumor cell motility, aggressiveness, and epithelial-mesenchymal transition (EMT). In gastrointestinal malignancies—including gastric, hepatic, colorectal, esophageal, gallbladder, and pancreatic cancers—SUMOylation drives tumor growth, metastasis, and invasiveness by reprogramming metabolic processes, signaling networks, and the surrounding tumor niche. Additionally, it contributes to resistance against chemotherapy and radiotherapy.

Understanding the molecular basis of SUMOylation not only underscores its significance in oncogenesis but also provides a foundation for developing novel anticancer therapies.

SUMO蛋白（SUMO1-5）与特定靶标的共价附着调节蛋白活性、稳定性和亚细胞分布，是一种重要的翻译后修饰。该过程由一系列酶介导，包括E1、E2、E3连接酶和deSUMOylation酶，从而精确控制多种生物功能，如基因表达、细胞周期调节、DNA损伤修复、信号级联和代谢途径。sumo酰化酶的失调通过增强肿瘤细胞的运动性、侵袭性和上皮-间质转化（EMT），有助于癌症的发生和治疗抵抗。在胃肠道恶性肿瘤中，包括胃癌、肝癌、结肠直肠癌、食管癌、胆囊癌和胰腺癌，sumoylation通过重编程代谢过程、信号网络和周围肿瘤生态位驱动肿瘤生长、转移和侵袭性。此外，它有助于抵抗化疗和放疗。了解SUMOylation的分子基础不仅强调了其在肿瘤发生中的重要性，而且为开发新的抗癌疗法提供了基础。

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引用次数: 0

Emerging and Re-emerging viral infections and their ocular manifestations: A focus on ocular neovascularization 新发和再发病毒感染及其眼部表现：眼部新生血管的焦点。

IF 10.3 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-12-01 Epub Date: 2025-09-29 DOI: 10.1016/j.mam.2025.101396

Dan Li , Qing Ye , Jianhao Bai , Wencui Wan

Emerging and re-emerging viral infections represent a significant and escalating global health concern, frequently associated with a spectrum of systemic complications. Among these, ocular manifestations are increasingly recognized, contributing substantially to visual morbidity. The present review aims to provide an overview of the ocular sequelae of major emerging and re-emerging viral pathogens, highlighting their suggested and established roles in ocular neovascularization (ONV). It discusses the virological and immunological mechanisms, including direct viral cytopathic effects, virally-induced inflammation, dysregulation of angiogenic and anti-angiogenic factors (e.g., Vascular Endothelial Growth Factor), and activation of hypoxia-inducible pathways, which can contribute to neovascular processes in various ocular compartments such as the cornea, iris, retina, and choroid. The major viral agents addressed in this review are Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Human Immunodeficiency Virus (HIV), West Nile virus (WNV), Dengue Virus (DENV), and other viruses with known or suspected ONV association. This study reviewed and summarized the literature regarding case reports and experimental models describing the association of these viral agents with ONV. Furthermore, it addresses diagnostic considerations and therapeutic strategies. Understanding the intricate interplay between these viral infections and ocular neovascular pathways is crucial for developing targeted therapeutic strategies to prevent vision loss in affected populations.

新出现和再出现的病毒感染是一个重大的和不断升级的全球卫生问题，通常与一系列系统性并发症有关。其中，眼部表现越来越被认识到，这是造成视力发病率的主要原因。本文综述了主要新出现和再出现的病毒性病原体的眼部后遗症，重点介绍了它们在眼部新生血管（ONV）中的作用。它讨论了病毒学和免疫学机制，包括直接的病毒细胞病变作用，病毒诱导的炎症，血管生成和抗血管生成因子（如血管内皮生长因子）的失调，以及缺氧诱导途径的激活，这些途径可以促进角膜，虹膜，视网膜和脉络膜等各种眼腔室的新血管过程。本综述涉及的主要病毒因子有严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）、人类免疫缺陷病毒（HIV）、西尼罗河病毒（WNV）、登革热病毒（DENV）以及其他已知或疑似与ONV相关的病毒。本研究回顾并总结了有关病例报告和实验模型的文献，这些文献描述了这些病毒制剂与ONV的关联。此外，它解决了诊断考虑和治疗策略。了解这些病毒感染与眼部新生血管通路之间复杂的相互作用，对于制定有针对性的治疗策略以预防受影响人群的视力丧失至关重要。

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引用次数: 0

Antisense oligonucleotides for inherited retinal diseases: a comprehensive review 遗传性视网膜疾病的反义寡核苷酸研究综述。

IF 10.3 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-12-01 Epub Date: 2025-10-01 DOI: 10.1016/j.mam.2025.101416

Hossein D. Banadaki , Alejandro Garanto , Rob W.J. Collin

Inherited retinal diseases (IRDs) are a genetically and clinically heterogeneous group of disorders that cause progressive vision loss and often lead to blindness. The complexity of these conditions arises from pathogenic variants in over 330 different genes, making the development of effective treatments highly challenging. Antisense oligonucleotides (ASOs) have emerged as a promising therapeutic approach for IRDs, offering precise regulation of transcript expression and composition. Unlike traditional gene augmentation therapies, ASOs provide a flexible and sequence-specific strategy by modulating splicing patterns, blocking translation, or promoting RNA degradation. Advancements in ASO chemistry, including backbone and sugar modifications, have significantly improved their uptake, stability, specificity, and therapeutic efficacy, facilitating their application in a variety of diseases. This review provides a comprehensive analysis of ASO-based strategies for IRDs, touching upon their mechanisms of action, chemical modifications, delivery strategies, and current clinical advancements. Additionally, we discuss the challenges that remain, such as off-target effects, delivery barriers, and long-term safety concerns, while highlighting future innovations that may enhance the efficacy and safety of ASOs and broaden their clinical applicability. As ASO-based therapies continue to progress through preclinical and clinical development, they hold significant potential to reshape the therapeutic landscape for IRDs, offering personalized and targeted treatments for patients with these devastating conditions.

遗传性视网膜疾病（IRDs）是一种遗传和临床异质性的疾病，可导致进行性视力丧失并经常导致失明。这些疾病的复杂性源于330多种不同基因的致病变异，这使得开发有效的治疗方法极具挑战性。反义寡核苷酸（ASOs）已成为一种有前景的治疗IRDs的方法，可以精确调节转录物的表达和组成。与传统的基因增强疗法不同，ASOs通过调节剪接模式、阻断翻译或促进RNA降解，提供了一种灵活的序列特异性策略。ASO化学的进步，包括骨架和糖修饰，显著提高了它们的吸收、稳定性、特异性和治疗效果，促进了它们在多种疾病中的应用。本文综述了基于aso的ird治疗策略的综合分析，涉及其作用机制、化学修饰、给药策略和当前的临床进展。此外，我们讨论了仍然存在的挑战，如脱靶效应、给药障碍和长期安全性问题，同时强调了未来可能提高aso疗效和安全性并扩大其临床适用性的创新。随着基于aso的疗法通过临床前和临床开发不断取得进展，它们具有重塑ird治疗前景的巨大潜力，为患有这些破坏性疾病的患者提供个性化和靶向治疗。

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引用次数: 0

Neuroteratogenic mechanisms of Zika virus (ZIKV) infection: Insights into fetal brain development disruption and congenital Zika syndrome: A systematic review 寨卡病毒（ZIKV）感染的神经致畸机制：胎儿大脑发育中断和先天性寨卡综合征的见解：系统综述。

IF 10.3 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-12-01 Epub Date: 2025-10-26 DOI: 10.1016/j.mam.2025.101418

Samira Sanami , Seyedeh Zahra Banihashemian , Saghar Amirpour , Farnaz Alibabaei , Ali Babaeizad , Mohammad Yousefi , Majid Eslami

The Zika virus (ZIKV), a mosquito-borne Flavivirus, has emerged as a global health threat due to its severe neuroteratogenic effects, particularly during pregnancy. This mechanistic-to-translational synthesis examines how ZIKV disrupts fetal brain development and links molecular events to clinical manifestations of Congenital Zika Syndrome (CZS). Our review advances prior summaries by presenting a unifying neural progenitor cell (NPC)-centric pathway framework that integrates viral entry, host signaling disruption, cell fate outcomes, and imaging correlates. Once transmitted vertically, the virus targets NPCs, impairing proliferation, triggering apoptosis, and halting the cell cycle. It modulates host pathways such as PI3K-Akt-mTOR and p53 to enhance autophagy, avoid immune detection, and sustain replication. ZIKV also interferes with RNA interference and synaptic formation, contributing to cortical thinning, ventriculomegaly, and agenesis of the corpus callosum. Inflammatory responses further exacerbate tissue damage as ZIKV activates TLRs and inflammasomes, increasing proinflammatory cytokines and pyroptosis. Brain organoid and imaging studies highlight the virus’s NPC tropism and capacity for lasting neurodevelopmental impairment—even in normocephalic infants. Importantly, ZIKV exhibits SOX2-dependent permissiveness with integrin αvβ5 functioning as a key dependency/attachment factor in neural and glioblastoma stem cells, distinguishing transcriptional state from receptor function. This intersection of neurotropism and potential oncolytic activity underscores the dual pathogenic and therapeutic implications of ZIKV. Literature was synthesized according to a predefined search strategy, with evidence appraised for quality, strengths, and limitations. This review highlights mechanistic pathways linking viral replication, immune modulation, and disrupted neurodevelopment, emphasizing implications for surveillance, therapeutic targets, and maternal-fetal health preparedness.

寨卡病毒（ZIKV）是一种蚊子传播的黄病毒，由于其严重的神经致畸作用，特别是在怀孕期间，已成为全球健康威胁。这种从机械到翻译的综合研究了寨卡病毒如何破坏胎儿大脑发育，并将分子事件与先天性寨卡综合征（CZS）的临床表现联系起来。我们的综述通过提出一个统一的神经祖细胞（NPC）中心通路框架来推进先前的总结，该框架整合了病毒进入、宿主信号中断、细胞命运结局和成像相关因素。一旦垂直传播，病毒就会以npc为目标，损害增殖，引发细胞凋亡，并停止细胞周期。它调节宿主途径，如PI3K-Akt-mTOR和p53，以增强自噬，避免免疫检测，并维持复制。寨卡病毒还干扰RNA干扰和突触形成，导致皮层变薄、脑室增大和胼胝体发育不全。由于ZIKV激活tlr和炎性小体，增加促炎细胞因子和焦亡，炎症反应进一步加剧了组织损伤。脑类器官和成像研究强调了该病毒的NPC倾向性和持久神经发育损伤的能力，即使在正常头型婴儿中也是如此。重要的是，ZIKV表现出sox2依赖的许可性，整合素αvβ5作为神经和胶质母细胞瘤干细胞的关键依赖/附着因子，将转录状态与受体功能区分开来。这种嗜神经性和潜在溶瘤活性的交叉强调了寨卡病毒的双重致病和治疗意义。根据预定义的检索策略对文献进行综合，并对证据的质量、优势和局限性进行评价。这篇综述强调了连接病毒复制、免疫调节和神经发育中断的机制途径，强调了监测、治疗靶点和母胎健康准备的意义。

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引用次数: 0

Post-translational modifications: Bridging viral infections and inflammatory bowel disease 翻译后修饰：桥接病毒感染和炎症性肠病。

IF 10.3 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-12-01 Epub Date: 2025-10-06 DOI: 10.1016/j.mam.2025.101417

Junbo Xiao , Yi Han , Kezhen Liu , Xiaotong Wang , Shizhe Li , Jun Yi , Xiaowei Liu

Macrophages are key innate immune cells that defend against pathogens, maintain tissue homeostasis, and regulate inflammation. A complex network of post-translational modifications (PTMs) controls the flexibility and adaptability of macrophage functions. These modifications change the structure, function, location, and interactions of proteins through covalent mechanisms such as phosphorylation, ubiquitination, SUMOylation, acetylation, and glycosylation. This enables macrophages to respond quickly and accurately to changes in their microenvironment. Dysregulated macrophage function is pivotal to the pathophysiology of inflammatory bowel disease (IBD) and the resultant outcomes following viral infections. Recent evidence suggests that macrophage PTMs provide a mechanistic link between IBD and viral infection. Viral infections may accelerate disease onset or exacerbate IBD activity. Viruses exploit the PTM machinery of host cells for their replication and immune evasion. This review discusses how PTM changes in macrophages caused by viral infections can lead to a long-lasting, pro-inflammatory state that could tip the balance of intestinal immunity toward chronic IBD. We elucidate the functions of traditional PTMs such as phosphorylation, ubiquitination, SUMOylation, acetylation, and glycosylation, in conjunction with emerging modifications such as lactylation and citrullination (deimination). We emphasize their distinct roles in both antiviral responses and IBD pathogenesis, while also exploring therapeutic strategies targeting PTM pathways.

巨噬细胞是防御病原体、维持组织稳态和调节炎症的关键先天免疫细胞。一个复杂的翻译后修饰（PTMs）网络控制着巨噬细胞功能的灵活性和适应性。这些修饰通过共价机制改变蛋白质的结构、功能、位置和相互作用，如磷酸化、泛素化、SUMOylation、乙酰化和糖基化。这使得巨噬细胞能够快速准确地对微环境的变化做出反应。巨噬细胞功能失调对炎症性肠病（IBD）的病理生理和病毒感染后的结果至关重要。最近的证据表明，巨噬细胞PTMs提供了IBD和病毒感染之间的机制联系。病毒感染可能加速疾病发作或加重IBD活动。病毒利用宿主细胞的PTM机制进行复制和免疫逃避。这篇综述讨论了病毒感染引起的巨噬细胞PTM变化如何导致长期的促炎状态，从而使肠道免疫平衡向慢性IBD倾斜。我们阐明了传统PTMs的功能，如磷酸化、泛素化、sumo化、乙酰化和糖基化，以及新兴的修饰，如乳酸化和瓜氨酸化（脱胺化）。我们强调它们在抗病毒反应和IBD发病机制中的独特作用，同时也探索了针对PTM途径的治疗策略。

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引用次数: 0

The bidirectional link between diabetes and pancreatic cancer: A diagnostic aid, risk factor, and potential target for future therapy 糖尿病和胰腺癌之间的双向联系：一种诊断辅助、危险因素和未来治疗的潜在目标

IF 10.3 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-12-01 Epub Date: 2025-09-25 DOI: 10.1016/j.mam.2025.101414

Kevin Verhoeff, A.M. James Shapiro

Historically, patients with pancreatic cancer presented with hyperglycemia and glycemic intolerance, leading to a hypothesis that diabetes may be associated with pancreatic ductal adenocarcinoma (PDAC). Nearly 50 years later, our understanding about the association and pathophysiological link between diabetes and PDAC continues to expand. What has been elucidated is that new-onset diabetes, especially in patients with weight loss or over the age of 50, may be an early clinical sign of PDAC. Additionally, long-standing diabetes remains an independent risk factor for development of PDAC. The pathophysiology of both new-onset and long-standing diabetes and PDAC is closely linked to non-alcoholic steatopancreatitis, the local inflammatory microenvironment, and metabolic alterations that bidirectionally arise from and worsen diabetes. This review summarizes current evidence evaluating the association between diabetes and pancreatic cancer. We also review the pathophysiology of this interaction, and discuss how understanding these mechanism may allow prevention, diagnosis, and treatment of pancreatic malignancy.

历史上，胰腺癌患者表现为高血糖和血糖不耐受，导致糖尿病可能与胰腺导管腺癌（PDAC）相关的假设。近50年后，我们对糖尿病和PDAC之间的关联和病理生理联系的理解继续扩大。已经阐明的是，新发糖尿病，特别是体重减轻或50岁以上的患者，可能是PDAC的早期临床症状。此外，长期糖尿病仍然是PDAC发展的独立危险因素。新发和长期糖尿病和PDAC的病理生理学与非酒精性脂肪性胰腺炎、局部炎症微环境和双向引起和加重糖尿病的代谢改变密切相关。本文综述了目前评价糖尿病和胰腺癌之间关系的证据。我们还回顾了这种相互作用的病理生理学，并讨论了如何理解这些机制可能有助于预防、诊断和治疗胰腺恶性肿瘤。

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