Molecular Aspects of Medicine最新文献

英文中文

Metabolic reprogramming of drug resistance in pancreatic cancer: mechanisms and effects 胰腺癌耐药的代谢重编程：机制和影响

IF 8.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-06-01 Epub Date: 2025-05-20 DOI: 10.1016/j.mam.2025.101368

Jinyi Zhang , Xueqing Kong , Boyan Zhou , Rui Li , Zhaoan Yu , Jinrong Zhu , Qing Xi , Yan Li , Zichao Zhao , Rongxin Zhang

Pancreatic cancer is a highly aggressive gastrointestinal malignancy, often termed the “king of cancers” due to its notoriously high mortality rate. Its clinical characteristics, including late diagnosis, low surgical resectability, high recurrence rates, significant chemoresistance, and poor prognosis have collectively driven the persistent rise in incidence and mortality. Despite ongoing advancements in therapeutic strategies, the management of pancreatic cancer, particularly at advanced stages, remains challenging. Chemotherapy remains the mainstay of current treatment. However, the prevalent problem of chemotherapy resistance poses a significant obstacle to effective treatment. Metabolic reprogramming, characterized by alterations in glucose metabolism, lipid biosynthesis, and amino acid utilization, supports the high energy demands and rapid proliferation of cancer cells. Emerging evidence suggests that these metabolic changes, possibly mediated by epigenetic mechanisms, also contribute to tumorigenesis and metastasis. These findings highlight the critical role of metabolic alterations in pancreatic cancer pathogenesis. This review explores the relationship between metabolic reprogramming and chemotherapy resistance, discussing underlying mechanisms and summarizing preclinical studies and drug development targeting metabolism. The aim is to provide a comprehensive perspective on potential therapeutic strategies for pancreatic cancer.

胰腺癌是一种高度侵袭性的胃肠道恶性肿瘤，由于其众所周知的高死亡率，常被称为“癌症之王”。其临床特点，包括诊断晚，手术可切除性低，复发率高，化疗耐药明显，预后差，共同推动发病率和死亡率持续上升。尽管治疗策略不断进步，但胰腺癌的管理，特别是在晚期，仍然具有挑战性。化疗仍然是目前治疗的主要方法。然而，普遍存在的化疗耐药问题对有效治疗构成了重大障碍。代谢重编程以葡萄糖代谢、脂质生物合成和氨基酸利用的改变为特征，支持癌细胞的高能量需求和快速增殖。新的证据表明，这些代谢变化，可能是由表观遗传机制介导的，也有助于肿瘤的发生和转移。这些发现强调了代谢改变在胰腺癌发病机制中的关键作用。本文综述了代谢重编程与化疗耐药之间的关系，讨论了其潜在机制，并总结了针对代谢的临床前研究和药物开发。目的是为胰腺癌的潜在治疗策略提供一个全面的视角。

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引用次数: 0

Metabolic reprogramming shapes post-translational modification in macrophages 巨噬细胞的代谢重编程影响翻译后修饰

IF 8.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-04-01 Epub Date: 2025-02-19 DOI: 10.1016/j.mam.2025.101338

Ziyi Han , Yinhao Shen , Yuqi Yan , Peng Bin , Meimei Zhang , Zhending Gan

Polarized macrophages undergo metabolic reprogramming, as well as extensive epigenetic and post-translational modifications (PTMs) switch. Metabolic remodeling and dynamic changes of PTMs lead to timely macrophage response to infection or antigenic stimulation, as well as its transition from a pro-inflammatory to a reparative phenotype. The transformation of metabolites in the microenvironment also determines the PTMs of macrophages. Here we reviewed the current understanding of the altered metabolites of glucose, lipids and amino acids in macrophages shape signaling and metabolism pathway during macrophage polarization via PTMs, and how these metabolites in some macrophage-associated diseases affect disease progression by shaping macrophage PTMs.

极化巨噬细胞经历代谢重编程，以及广泛的表观遗传和翻译后修饰（PTMs）开关。ptm的代谢重塑和动态变化导致巨噬细胞对感染或抗原刺激的及时反应，并从促炎表型向修复表型转变。微环境中代谢物的转化也决定了巨噬细胞的ptm。本文综述了目前对巨噬细胞极化过程中葡萄糖、脂质和氨基酸代谢物在巨噬细胞形成信号和代谢途径中的改变，以及这些代谢物在一些巨噬细胞相关疾病中如何通过塑造巨噬细胞PTMs影响疾病进展的认识。

引用次数: 0

Disentangling the nutrition-microbiota liaison in inflammatory bowel disease 解开炎症性肠病中营养-微生物群的联系

IF 8.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-04-01 Epub Date: 2025-02-07 DOI: 10.1016/j.mam.2025.101349

Marilina Florio , Lucilla Crudele , Fabio Sallustio , Antonio Moschetta , Marica Cariello , Raffaella M. Gadaleta

Inflammatory Bowel Disease (IBD) is a set of chronic intestinal inflammatory disorders affecting the gastrointestinal (GI) tract. Beside compromised intestinal barrier function and immune hyperactivation, a common IBD feature is dysbiosis, characterized by a reduction of some strains of Firmicutes, Bacteroidetes, Actinobacteria and an increase in Proteobacteria and pathobionts. Emerging evidence points to diet and nutrition-dependent gut microbiota (GM) modulation, as etiopathogenetic factors and adjuvant therapies in IBD. Currently, no nutritional regimen shows universal efficacy, and advice are controversial, especially those involving restrictive diets potentially resulting in malnutrition. This review provides an overview of the role of macronutrients, dietary protocols and GM modulation in IBD patients. A Western-like diet contributes to an aberrant mucosal immune response to commensal bacteria and impairment of the intestinal barrier integrity, thereby triggering intestinal inflammation. Conversely, a Mediterranean nutritional pattern appears to be one of the most beneficial dietetic regimens able to restore the host intestinal physiology, by promoting eubiosis and preserving the intestinal barrier and immune function, which in turn create a virtuous cycle improving patient adherence to the pattern. Further clinical studies are warranted, to corroborate current IBD nutritional guidelines, and develop more accurate models to move forward precision nutrition and ameliorate patients’ quality of life.

炎症性肠病（IBD）是一组影响胃肠道的慢性肠道炎症性疾病。除了肠道屏障功能受损和免疫过度激活外，IBD的一个常见特征是生态失调，其特征是某些厚壁菌门、杆菌门、放线菌门的菌株减少，而变形菌门和病原体增加。新出现的证据表明，饮食和营养依赖的肠道微生物群（GM）调节是IBD的发病因素和辅助治疗。目前，没有一种营养方案显示出普遍的功效，建议也存在争议，特别是那些涉及可能导致营养不良的限制性饮食的建议。本文综述了宏量营养素、饮食方案和转基因调节在IBD患者中的作用。西式饮食会导致粘膜对共生菌的异常免疫反应，损害肠道屏障的完整性，从而引发肠道炎症。相反，地中海营养模式似乎是最有益的饮食方案之一，能够通过促进益生菌和保护肠道屏障和免疫功能来恢复宿主肠道生理，从而形成良性循环，提高患者对这种模式的依从性。进一步的临床研究是有必要的，以证实目前的IBD营养指南，并开发更准确的模型，以推进精确营养和改善患者的生活质量。

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引用次数: 0

The recent blooming of therapeutic aptamers 最近出现的治疗适体

IF 8.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-04-01 Epub Date: 2025-02-10 DOI: 10.1016/j.mam.2025.101350

Valeriana Cesarini , Silvia Lucia Appleton , Vittorio de Franciscis , Daniele Catalucci

In the dynamic landscape of biomedical research, therapeutic RNA aptamers have recently come to the forefront, showing significant potential in diagnostics and therapeutics. This review aims to raise awareness of aptamer technology within the scientific community by exploring the progress made in the therapeutic field, from the lessons learned in research to the future opportunities and impact that these innovative molecules are increasingly having on society to meet current health needs, i.e. targeted and personalized therapies.

在生物医学研究的动态环境中，治疗性RNA适配体最近走到了前沿，在诊断和治疗方面显示出巨大的潜力。本综述旨在通过探索治疗领域取得的进展，提高科学界对适体技术的认识，从研究中的经验教训到这些创新分子对满足当前健康需求（即针对性和个性化治疗）的未来机会和影响。

引用次数: 0

When to suspect and how properly early detect and treat patients with endemic mycoses 何时怀疑以及如何正确地早期发现和治疗地方性真菌病患者

IF 8.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-04-01 Epub Date: 2025-02-05 DOI: 10.1016/j.mam.2025.101348

Arnaldo L. Colombo , Paula M. Peçanha-Pietrobom , Daniel Wagner de C.L. Santos , Diego H. Caceres

Endemic mycoses are caused by dimorphic fungi and eventually molds, as the case of implantation mycoses. In general, these diseases are acquired through trauma or inhalation of fungal elements in the environment, and less frequently by zoonotic acquisition or transmitted during organ transplantation. The target population for endemic mycoses is usually represented by normal hosts with low-income and intensive outdoor activities. Awareness of these diseases remains limited, even in regions with high prevalence, resulting in delayed diagnosis, and affecting the quality of life and outcomes of patients who suffer from these entities. In this review, we summarized relevant information about epidemiological, clinical, diagnostic, and treatment aspects of the most common endemic mycoses, including blastomycosis, coccidioidomycosis, histoplasmosis, paracoccidioidomycoses, talaromycosis, and implantation mycoses. The main goal of this review is to provide key concepts in terms of when to suspect, how early diagnose, and properly treat patients with these mycoses.

地方性真菌病是由二态真菌引起的，最终由霉菌引起，如着床性真菌病。一般来说，这些疾病是通过外伤或吸入环境中的真菌元素而获得的，较少由人畜共患病或在器官移植期间传播。地方性真菌病的目标人群通常以低收入和密集户外活动的正常宿主为代表。即使在发病率高的地区，对这些疾病的认识仍然有限，导致诊断延误，并影响患有这些疾病的患者的生活质量和结果。在这篇综述中，我们总结了最常见的地方性真菌病的流行病学、临床、诊断和治疗方面的相关信息，包括芽孢菌病、球孢子菌病、组织浆菌病、副球孢子菌病、talaromycosis和着床真菌病。本综述的主要目的是提供关于何时怀疑、如何早期诊断和正确治疗这些真菌病患者的关键概念。

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引用次数: 0

The molecular code of kidney cancer: A path of discovery for gene mutation and precision therapy 肾癌的分子密码：基因突变和精准治疗的发现之路。

IF 8.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-02-01 Epub Date: 2025-01-01 DOI: 10.1016/j.mam.2024.101335

Deqian Xie , Guandu Li , Zunwen Zheng , Xiaoman Zhang , Shijin Wang , Bowen Jiang , Xiaorui Li , Xiaoxi Wang , Guangzhen Wu

Renal cell carcinoma (RCC) is a malignant tumor with highly heterogeneous and complex molecular mechanisms. Through systematic analysis of TCGA, COSMIC and other databases, 24 mutated genes closely related to RCC were screened, including VHL, PBRM1, BAP1 and SETD2, which play key roles in signaling pathway transduction, chromatin remodeling and DNA repair. The PI3K/AKT/mTOR signaling pathway is particularly important in the pathogenesis of RCC. Mutations in genes such as PIK3CA, MTOR and PTEN are closely associated with metabolic abnormalities and tumor cell proliferation. Clinically, mTOR inhibitors and VEGF-targeted drugs have shown significant efficacy in personalized therapy. Abnormal regulation of metabolic reprogramming, especially glycolysis and glutamine metabolic pathways, provides tumor cells with continuous energy supply and survival advantages, and GLS1 inhibitors have shown promising results in preclinical studies. This paper also explores the potential of immune checkpoint inhibitors in combination with other targeted drugs, as well as the promising application of nanotechnology in drug delivery and targeted therapy. In addition, unique molecular mechanisms are revealed and individualized therapeutic strategies are explored for specific subtypes such as TFE3, TFEB rearrangement type and SDHB mutant type. The review summarizes the common gene mutations in RCC and their molecular mechanisms, emphasizes their important roles in tumor diagnosis, treatment and prognosis, and looks forward to the application prospects of multi-pathway targeted therapy, metabolic targeted therapy, immunotherapy and nanotechnology in RCC treatment, providing theoretical support and clinical guidance for individualized treatment and new drug development.

肾细胞癌（RCC）是一种具有高度异质性和复杂分子机制的恶性肿瘤。通过对TCGA、COSMIC等数据库的系统分析，筛选出24个与RCC密切相关的突变基因，包括VHL、PBRM1、BAP1和SETD2，这些基因在信号通路转导、染色质重塑和DNA修复中发挥关键作用。PI3K/AKT/mTOR信号通路在RCC的发病机制中尤为重要。PIK3CA、MTOR和PTEN等基因突变与代谢异常和肿瘤细胞增殖密切相关。临床上，mTOR抑制剂和vegf靶向药物在个体化治疗中已显示出显著的疗效。异常调节代谢重编程，特别是糖酵解和谷氨酰胺代谢途径，为肿瘤细胞提供了持续的能量供应和生存优势，GLS1抑制剂在临床前研究中显示出良好的效果。本文还探讨了免疫检查点抑制剂与其他靶向药物联合的潜力，以及纳米技术在药物传递和靶向治疗中的应用前景。此外，还揭示了TFE3、TFEB重排型和SDHB突变型等特定亚型的独特分子机制，并探索了个体化治疗策略。综述了RCC常见基因突变及其分子机制，强调其在肿瘤诊断、治疗和预后中的重要作用，展望了多途径靶向治疗、代谢靶向治疗、免疫治疗和纳米技术在RCC治疗中的应用前景，为个体化治疗和新药开发提供理论支持和临床指导。

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引用次数: 0

The folding and misfolding of multidomain proteins 多结构域蛋白的折叠和错误折叠。

IF 8.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-02-01 Epub Date: 2025-01-09 DOI: 10.1016/j.mam.2025.101337

Stefano Gianni, Maurizio Brunori

Protein folding represents a vital process for any living organism. While significant insights have been gained from studying single-domain proteins, our current knowledge on the folding mechanisms of multidomain proteins remains relatively limited, primarily due to their inherent complexity. The principal aim of this review lies in summarizing the emerging view pertaining multi-domain folding, emphasizing their modular nature, which minimizes misfolding and facilitates evolutionary innovation. We discuss the energetic interplay between domains, highlighting particularly the cases where domain interactions lead to transient misfolded intermediates. These interactions can result in diverse effects, including cooperative folding and domain-specific perturbations, which are particularly relevant to the pathogenesis of neurodegenerative diseases like polyglutamine disorders. The review underscores the critical need to understand multidomain folding, to better comprehend and potentially mitigate the molecular underpinnings of protein misfolding diseases.

蛋白质折叠对任何生物体来说都是一个重要的过程。虽然从研究单域蛋白中获得了重要的见解，但我们目前对多域蛋白折叠机制的了解仍然相对有限，主要是由于它们固有的复杂性。本综述的主要目的在于总结有关多畴折叠的新兴观点，强调它们的模块化性质，从而最大限度地减少错误折叠并促进进化创新。我们讨论了区域之间的能量相互作用，特别强调了区域相互作用导致瞬态错误折叠中间体的情况。这些相互作用可导致多种影响，包括合作折叠和区域特异性扰动，这与神经退行性疾病（如多谷氨酰胺疾病）的发病机制特别相关。这篇综述强调了了解多结构域折叠的迫切需要，以便更好地理解和潜在地减轻蛋白质错误折叠疾病的分子基础。

引用次数: 0

Cancer vaccines: Target antigens, vaccine platforms and preclinical models 癌症疫苗：靶抗原、疫苗平台和临床前模型。

IF 8.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-02-01 Epub Date: 2024-12-03 DOI: 10.1016/j.mam.2024.101324

Francesca Ruzzi , Federica Riccardo , Laura Conti , Lidia Tarone , Maria Sofia Semprini , Elisabetta Bolli , Giuseppina Barutello , Elena Quaglino , Pier-Luigi Lollini , Federica Cavallo

This review provides a comprehensive overview of the evolving landscape of cancer vaccines, highlighting their potential to revolutionize tumor prevention. Building on the success of vaccines against virus-related cancers, such as HPV- and HBV-associated cervical and liver cancers, the current challenge is to extend these achievements to the prevention of non-viral tumors and the treatment of preneoplastic or early neoplastic lesions. This review analyzes the critical aspects of preventive anti-cancer vaccination, focusing on the choice of target antigens, the development of effective vaccine platforms and technologies, and the use of various model systems for preclinical testing, from laboratory rodents to companion animals.

这篇综述全面概述了癌症疫苗的发展前景，强调了它们在肿瘤预防方面的革命性潜力。在针对病毒相关癌症（如与人乳头瘤病毒和乙肝病毒相关的宫颈癌和肝癌）的疫苗取得成功的基础上，目前的挑战是将这些成就扩展到预防非病毒性肿瘤和治疗肿瘤前或早期肿瘤病变。本文分析了预防性抗癌疫苗接种的关键方面，重点是目标抗原的选择，有效疫苗平台和技术的发展，以及从实验室啮齿动物到伴侣动物的各种临床前试验模型系统的使用。

引用次数: 0

An updated systematic review about various effects of microplastics on cancer: A pharmacological and in-silico based analysis 关于微塑料对癌症的各种影响的最新系统综述：药理学和基于计算机的分析。

IF 8.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-02-01 Epub Date: 2025-01-04 DOI: 10.1016/j.mam.2024.101336

Akmaral Baspakova , Afshin Zare , Roza Suleimenova , Aidar B. Berdygaliev , Bibigul Karimsakova , Kymbat Tussupkaliyeva , Nadiar M. Mussin , Kulyash R. Zhilisbayeva , Nader Tanideh , Amin Tamadon

Microplastics (MPs) are known as substantial environmental and health threats because of their pervasive existence and potential function in human diseases. This study is the first research in which a comprehensive analysis of various impacts of MPs on cancer cells is performed through pharmacological and in silico approaches. Moreover, our results demonstrate that MPs have both promotive and suppressive impacts on cancer cells, changing some of the important features of these kinds of cells including cellular viability, migration, metastasis, and apoptosis. Furthermore, the present study displayed that AP-2 complex subunit mu-1 (AP2M1), Asialoglycoprotein receptor 2 (ASGR2), Bax inhibitor-1 (BI-1), and Ferritin Heavy Chain, and pivotal role in the progression of cancers mediated by MPs. Moreover, our in-silico analysis identified Goserelin, Paclitaxel, Raloxifene, Exemestane, Epirubicin, Trametinib, Vemurafenib, Pactitaxel, and Sorafenib as potential anticancer agents for curing MPS-based cancer. Besides, our results demonstrated that MPs can exacerbate the development of tumor cells by affecting some important mechanisms including oxidative stress, immune suppression, and adjusting of critical signaling pathways. Interestingly, some sorts of MPs also displayed suppressive effects on cancer cells in some particular contexts, highlighting their complicated biological roles in different biological interactions. Ultimately the present survey tries to demonstrate the crucial roles of MPs in cancer cells and the different mechanisms that occur in the mentioned cells in order to emphasize performing more studies about clarifying the roles of MPs in carcinogenesis.

由于微塑料的普遍存在和在人类疾病中的潜在作用，它们被认为是重大的环境和健康威胁。这项研究是第一个通过药理学和计算机方法对MPs对癌细胞的各种影响进行综合分析的研究。此外，我们的研究结果表明，MPs对癌细胞既有促进作用，也有抑制作用，改变了这些细胞的一些重要特征，包括细胞活力、迁移、转移和凋亡。此外，本研究还发现AP-2复合物亚基mu-1 （AP2M1）、亚洲糖蛋白受体2 （ASGR2）、Bax抑制剂-1 （BI-1）和铁蛋白重链在MPs介导的癌症进展中起关键作用。此外，我们的计算机分析发现戈舍雷林、紫杉醇、雷洛昔芬、依西美坦、表柔比星、曲美替尼、Vemurafenib、帕克他赛和索拉非尼是治疗mps型癌症的潜在抗癌药物。此外，我们的研究结果表明，MPs可以通过影响氧化应激、免疫抑制和关键信号通路的调节等重要机制来加剧肿瘤细胞的发展。有趣的是，某些种类的MPs在某些特定情况下也表现出对癌细胞的抑制作用，突出了它们在不同生物相互作用中的复杂生物学作用。最后，本研究试图证明MPs在癌细胞中的关键作用以及在上述细胞中发生的不同机制，以强调进行更多的研究来阐明MPs在癌变中的作用。

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引用次数: 0

Vaccines for cancer prevention and treatment 预防和治疗癌症的疫苗。

IF 8.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine

Pub Date : 2025-02-01 Epub Date: 2024-12-13 DOI: 10.1016/j.mam.2024.101334

Federica Cavallo, Pier-Luigi Lollini

引用次数: 0

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