Molecular Aspects of Medicine最新文献

{"title":"Interactions between pathological and functional amyloid: A match made in Heaven or Hell?","authors":"Daniel E. Otzen ,&nbsp;Samuel Peña-Díaz ,&nbsp;Jeremias Widmann ,&nbsp;Anders Ogechi Hostrup Daugberg ,&nbsp;Zhefei Zhang ,&nbsp;Yanting Jiang ,&nbsp;Chandrika Mittal ,&nbsp;Morten K.D. Dueholm ,&nbsp;Nikolaos Louros ,&nbsp;Huabing Wang ,&nbsp;Ibrahim Javed","doi":"10.1016/j.mam.2025.101351","DOIUrl":"10.1016/j.mam.2025.101351","url":null,"abstract":"<div><div>The amyloid state of proteins occurs in many different contexts in Nature and in modern society, ranging from the pathological kind (neurodegenerative diseases and amyloidosis) via man-made forms (food processing and – to a much smaller extent - protein biologics) to functional versions (bacterial biofilm, peptide hormones and signal transmission). These classes all come together in the human body which endogenously produces amyloidogenic protein able to form pathological human amyloid (PaHA), hosts a microbiome which continuously makes functional bacterial amyloid (FuBA) and ingests food which can contain amyloid. This can have grave consequences, given that PaHA can spread throughout the body in a “hand-me-down” fashion from cell to cell through small amyloid fragments, which can kick-start growth of new amyloid wherever they encounter monomeric amyloid precursors. Amyloid proteins can also self- and cross-seed across dissimilar peptide sequences. While it is very unlikely that ingested amyloid plays a role in this crosstalk, FuBA-PaHA interactions are increasingly implicated <em>in vivo</em> amyloid propagation. We are now in a position to understand the structural and bioinformatic basis for this cross-talk, thanks to the very recently obtained atomic-level structures of the two major FuBAs CsgA (<em>E. coli</em>) and FapC (<em>Pseudomonas</em>). While there are many reports of homology-driven heterotypic interactions between different PaHA, the human proteome does not harbor significant homology to CsgA and FapC. Yet we and others have uncovered significant cross-stimulation (and in some cases inhibition) of FuBA and PaHA both <em>in vitro</em> and <em>in vivo,</em> which we here rationalize based on structure and sequence. These interactions have important consequences for the transmission and development of neurodegenerative diseases, not least because FuBA and PaHA can come into contact via the gut-brain interface, recurrent infections with microbes and potentially even through invasive biofilm in the brain. Whether FuBA and PaHA first interact in the gut or the brain, they can both stimulate and block each other's aggregation as well as trigger inflammatory responses. The microbiome may also affect amyloidogenesis in other ways, <em>e.g.</em> through their own chaperones which recognize and block growth of both PaHA and FuBA as we show both experimentally and computationally. Heterotypic interactions between and within PaHA and FuBA both <em>in vitro</em> and <em>in vivo</em> are a vital part of the amyloid phenomenon and constitute a vibrant and exciting frontier for future research.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"103 ","pages":"Article 101351"},"PeriodicalIF":8.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic reprogramming shapes post-translational modification in macrophages","authors":"Ziyi Han ,&nbsp;Yinhao Shen ,&nbsp;Yuqi Yan ,&nbsp;Peng Bin ,&nbsp;Meimei Zhang ,&nbsp;Zhending Gan","doi":"10.1016/j.mam.2025.101338","DOIUrl":"10.1016/j.mam.2025.101338","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"102 ","pages":"Article 101338"},"PeriodicalIF":8.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The recent blooming of therapeutic aptamers","authors":"Valeriana Cesarini ,&nbsp;Silvia Lucia Appleton ,&nbsp;Vittorio de Franciscis ,&nbsp;Daniele Catalucci","doi":"10.1016/j.mam.2025.101350","DOIUrl":"10.1016/j.mam.2025.101350","url":null,"abstract":"<div><div>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, <em>i.e.</em> targeted and personalized therapies.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"102 ","pages":"Article 101350"},"PeriodicalIF":8.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disentangling the nutrition-microbiota liaison in inflammatory bowel disease","authors":"Marilina Florio ,&nbsp;Lucilla Crudele ,&nbsp;Fabio Sallustio ,&nbsp;Antonio Moschetta ,&nbsp;Marica Cariello ,&nbsp;Raffaella M. Gadaleta","doi":"10.1016/j.mam.2025.101349","DOIUrl":"10.1016/j.mam.2025.101349","url":null,"abstract":"<div><div>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 <em>Firmicutes</em>, <em>Bacteroidetes</em>, <em>Actinobacteria</em> and an increase in <em>Proteobacteria</em> 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.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"102 ","pages":"Article 101349"},"PeriodicalIF":8.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When to suspect and how properly early detect and treat patients with endemic mycoses","authors":"Arnaldo L. Colombo ,&nbsp;Paula M. Peçanha-Pietrobom ,&nbsp;Daniel Wagner de C.L. Santos ,&nbsp;Diego H. Caceres","doi":"10.1016/j.mam.2025.101348","DOIUrl":"10.1016/j.mam.2025.101348","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"102 ","pages":"Article 101348"},"PeriodicalIF":8.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143295999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The molecular code of kidney cancer: A path of discovery for gene mutation and precision therapy","authors":"Deqian Xie ,&nbsp;Guandu Li ,&nbsp;Zunwen Zheng ,&nbsp;Xiaoman Zhang ,&nbsp;Shijin Wang ,&nbsp;Bowen Jiang ,&nbsp;Xiaorui Li ,&nbsp;Xiaoxi Wang ,&nbsp;Guangzhen Wu","doi":"10.1016/j.mam.2024.101335","DOIUrl":"10.1016/j.mam.2024.101335","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"101 ","pages":"Article 101335"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The folding and misfolding of multidomain proteins","authors":"Stefano Gianni,&nbsp;Maurizio Brunori","doi":"10.1016/j.mam.2025.101337","DOIUrl":"10.1016/j.mam.2025.101337","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"101 ","pages":"Article 101337"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer vaccines: Target antigens, vaccine platforms and preclinical models","authors":"Francesca Ruzzi ,&nbsp;Federica Riccardo ,&nbsp;Laura Conti ,&nbsp;Lidia Tarone ,&nbsp;Maria Sofia Semprini ,&nbsp;Elisabetta Bolli ,&nbsp;Giuseppina Barutello ,&nbsp;Elena Quaglino ,&nbsp;Pier-Luigi Lollini ,&nbsp;Federica Cavallo","doi":"10.1016/j.mam.2024.101324","DOIUrl":"10.1016/j.mam.2024.101324","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"101 ","pages":"Article 101324"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An updated systematic review about various effects of microplastics on cancer: A pharmacological and in-silico based analysis","authors":"Akmaral Baspakova ,&nbsp;Afshin Zare ,&nbsp;Roza Suleimenova ,&nbsp;Aidar B. Berdygaliev ,&nbsp;Bibigul Karimsakova ,&nbsp;Kymbat Tussupkaliyeva ,&nbsp;Nadiar M. Mussin ,&nbsp;Kulyash R. Zhilisbayeva ,&nbsp;Nader Tanideh ,&nbsp;Amin Tamadon","doi":"10.1016/j.mam.2024.101336","DOIUrl":"10.1016/j.mam.2024.101336","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"101 ","pages":"Article 101336"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaccines for cancer prevention and treatment","authors":"Federica Cavallo,&nbsp;Pier-Luigi Lollini","doi":"10.1016/j.mam.2024.101334","DOIUrl":"10.1016/j.mam.2024.101334","url":null,"abstract":"","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"101 ","pages":"Article 101334"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}