Molecular Aspects of Medicine最新文献_第3页

Cross-talk between cancer and diabetes: Exploring shared molecular pathways in cellular metabolism and signaling 癌症和糖尿病之间的交叉对话：探索细胞代谢和信号传导的共享分子途径。

IF 10.3 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-10-27 DOI: 10.1016/j.mam.2025.101420

Zhangzhi Tang , Nuo Xu , Pin Lyu , Hui Zhao , Wenjie Zheng

Diabetes and cancer are among the most prevalent chronic diseases globally, drawing increasing attention due to their shared features of metabolic and signaling dysregulation. Epidemiological evidence indicates that type 2 diabetes significantly elevates the risk of developing multiple types of tumors. This review highlights the key molecular intersections between diabetic pathophysiology and oncogenic processes, with a focus on how hyperinsulinemia and hyperglycemia contribute to tumor initiation and progression. These effects are primarily mediated through profound metabolic reprogramming, including hyperactivation of the hexosamine biosynthetic pathway (HBP) and the accumulation of advanced glycation end-products (AGEs), which promote sustained oxidative stress and chronic inflammation. Consequently, the tumor microenvironment (TME) undergoes substantial remodeling. The metabolism and function of immune cells are disrupted, promoting immune evasion. Meanwhile, cancer cells adapt by engaging mechanisms such as diabetes-induced epigenetic reprogramming, activation of the unfolded protein response (UPR), and alterations in the gut microbiota, thereby enhancing their survival advantage. Emerging evidence suggests that anti-diabetic agents targeting these metabolic intersections exhibit dual roles in cancer therapy, offering both therapeutic potential and potential risks. To address these complexities, future efforts should conduct multi-omics technologies to dissect the metabolic heterogeneity of diabetes-associated tumors, paving the way for precise and personalized therapeutic strategies for patients with this comorbidity.

糖尿病和癌症是全球最普遍的慢性疾病，由于其代谢和信号失调的共同特征而引起越来越多的关注。流行病学证据表明，2型糖尿病显著增加多种肿瘤发生的风险。这篇综述强调了糖尿病病理生理和致癌过程之间的关键分子交叉点，重点是高胰岛素血症和高血糖如何促进肿瘤的发生和进展。这些影响主要是通过深刻的代谢重编程介导的，包括己糖胺生物合成途径（HBP）的过度激活和晚期糖基化终产物（AGEs）的积累，后者促进了持续的氧化应激和慢性炎症。因此，肿瘤微环境（TME）经历了大量的重塑。免疫细胞的新陈代谢和功能被破坏，促进免疫逃避。与此同时，癌细胞通过参与糖尿病诱导的表观遗传重编程、未折叠蛋白反应（UPR）的激活和肠道微生物群的改变等机制来适应，从而增强了它们的生存优势。新出现的证据表明，针对这些代谢交叉点的抗糖尿病药物在癌症治疗中具有双重作用，既有治疗潜力，也有潜在风险。为了解决这些复杂的问题，未来的努力应该通过多组学技术来剖析糖尿病相关肿瘤的代谢异质性，为患有这种合并症的患者制定精确和个性化的治疗策略铺平道路。

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引用次数: 0

The crosstalk of neutrophil extracellular trap-inflammasome and their roles in disease progression 中性粒细胞胞外陷阱炎性体的串扰及其在疾病进展中的作用。

IF 10.3 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-10-27 DOI: 10.1016/j.mam.2025.101419

Jieqing Xiong , Jiaojiao Xue , Heqi Zhou , Wenxiu Qi , Haoyu Zhu

Neutrophil extracellular traps (NETs) are a network of fibrous structures composed of DNA, histones, and antimicrobial proteins released by neutrophils, which play a crucial role in the innate immune system's defense against infection. When neutrophils encounter pathogens, they can release NETs to capture and neutralize these invaders, preventing their spread and prompting other immune cells to destroy them. The classical inflammasome is a cytoplasmic polyprotein complex activated by infectious and/or non-infectious stimuli that activates the protease caspase-1 to induce pyroptosis and promotes the maturation and release of interleukin (IL)-1β and IL-18, while the non-classical inflammasome activates cysteinyl aspartate specific proteinase (caspase)-4/11 to induce pyroptosis. Inflammasome activation is also an important component of the innate immune response. This review elaborates on the constituent proteins and molecular regulation of NETs and inflammasomes, summarizes the crosstalk between NETs and inflammasomes and its negative effects in the disease process, and also discusses the therapeutic effects of drugs targeting NETs and/or inflammasomes on related diseases.

中性粒细胞胞外陷阱（NETs）是由中性粒细胞释放的DNA、组蛋白和抗菌蛋白组成的纤维结构网络，在先天免疫系统防御感染中起着至关重要的作用。当中性粒细胞遇到病原体时，它们可以释放net来捕获和中和这些入侵者，阻止它们的扩散，并促使其他免疫细胞摧毁它们。经典炎性小体是一种由感染性和/或非感染性刺激激活的细胞质多蛋白复合物，它激活蛋白酶caspase-1诱导细胞焦亡，并促进白细胞介素(IL)-1β和IL-18的成熟和释放，而非经典炎性小体激活半胱氨酸天冬氨酸特异性蛋白酶(caspase)-4/11诱导细胞焦亡。炎性小体活化也是先天免疫反应的重要组成部分。本文综述了NETs和炎性小体的组成蛋白及其分子调控，综述了NETs和炎性小体之间的串扰及其在疾病过程中的负面作用，并讨论了靶向NETs和/或炎性小体的药物对相关疾病的治疗效果。

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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 : 2025-10-26 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 : 2025-10-06 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

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 : 2025-10-01 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

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 : 2025-09-29 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

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 : 2025-09-26 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

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 : 2025-09-25 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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引用次数: 0

The multifunctionality of the caspase family of proteases: A new perspective beyond cell death caspase蛋白酶家族的多功能性：超越细胞死亡的新视角。

IF 10.3 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-09-18 DOI: 10.1016/j.mam.2025.101411

Jiaqi Li , Qingqing Zhai , Wangzheqi Zhang , Yisheng Chen , Changli Wang , Xiaoming Deng , Haoling Zhang , Zhiheng Lin , Yalin Zhu

Caspase family proteases, as aspartate-specific cysteine proteases, have long been considered to function exclusively in programmed cell death. However, emerging evidence indicates that their functions extends well beyond apoptosis. Members of this family exhibit numerous non-cell death functions through dynamic regulation of activity gradients and spatiotemporal localization, participating extensively in physiological processes such as neuronal synaptic remodeling, immune homeostasis regulation, and metabolic reprogramming, thereby forming a functional continuum from the molecular to the system level. Based on these novel functions, we propose a function-oriented classification of caspases into three categories: homeostatic, defensive, and remodeling types, while revealing their cross-category functional overlap. In addition, the development of conformation-specific inhibitors and microenvironment-responsive delivery systems provides precise regulatory tools for targeted therapy. This paper systematically summarizes the non-apoptotic functions of the caspase family and proposes a "spatiotemporal activity" dynamic model, opening new avenues for tumor therapy, neurodegenerative disease intervention, and immune disorder regulation.

Caspase家族蛋白酶作为天冬氨酸特异性半胱氨酸蛋白酶，长期以来被认为只在程序性细胞死亡中起作用。然而，新出现的证据表明，它们的功能远远超出了细胞凋亡。该家族成员通过动态调节活动梯度和时空定位表现出多种非细胞死亡功能，广泛参与神经突触重塑、免疫稳态调节和代谢重编程等生理过程，从而形成从分子到系统水平的功能连续体。基于这些新功能，我们将半胱天冬酶分为三类：稳态型、防御型和重塑型，同时揭示了它们的跨类别功能重叠。此外，构象特异性抑制剂和微环境响应递送系统的发展为靶向治疗提供了精确的调节工具。本文系统总结了caspase家族的非凋亡功能，提出了caspase家族的“时空活动”动态模型，为肿瘤治疗、神经退行性疾病干预、免疫失调调节等开辟了新的途径。

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引用次数: 0

The ocular immune system and Flaviviruses: A crossroad between defense and disease 眼免疫系统和黄病毒：防御和疾病之间的十字路口。

IF 10.3 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-09-16 DOI: 10.1016/j.mam.2025.101409

Yao Xu , Wei Zhu , Xiao-feng Zhang

Flaviviruses are emerging arthropod-borne viruses that cause severe endemic infections and epidemics on a global scale. Recent Zika virus outbreaks have highlighted a significant link between the virus and ocular abnormalities, increasing interest in the pathogenesis of Flaviviruses. Flavivirus pathogenesis involves a complex interplay between viral replication and immune responses, leading to a wide spectrum of human diseases. Flavivirus infections can cause ocular complications that are usually self-limiting but can result in irreversible visual impairment and vision loss. These complications can affect both the anterior and posterior segments of the eye, and symptoms can range from mild conjunctivitis to more severe conditions like uveitis and even the inflammation of the optic nerve. Ocular inflammation often arises from the immune system's response to viral infections. In ocular Flavivirus infections, the immune response aims to protect the eye, but it can sometimes lead to inflammation and tissue damage. In this review, we summarize the current knowledge of the major Flaviviruses (Zika, Dengue, Yellow Fever, and West Nile) reported to cause ocular manifestations in humans, with emphasis on viral immunopathogenesis. Hence, we discuss how Flaviviruses modulate immune responses and cause ocular manifestations.

黄病毒是一种新兴的节肢动物传播的病毒，在全球范围内引起严重的地方性感染和流行病。最近的寨卡病毒暴发突出了该病毒与眼部异常之间的重要联系，增加了人们对黄病毒发病机制的兴趣。黄病毒的发病机制涉及病毒复制和免疫反应之间复杂的相互作用，导致广泛的人类疾病。黄病毒感染可引起眼部并发症，通常是自限性的，但可导致不可逆的视力损害和视力丧失。这些并发症可以影响眼睛的前段和后段，症状可以从轻微的结膜炎到更严重的情况，如葡萄膜炎，甚至视神经炎症。眼部炎症通常是免疫系统对病毒感染的反应引起的。在眼部黄病毒感染中，免疫反应旨在保护眼睛，但有时会导致炎症和组织损伤。在这篇综述中，我们总结了目前已知的引起人类眼部症状的主要黄病毒（寨卡病毒、登革热病毒、黄热病病毒和西尼罗河病毒），重点介绍了病毒的免疫发病机制。因此，我们讨论黄病毒如何调节免疫反应和引起眼部表现。

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