Molecular Aspects of Medicine最新文献

{"title":"Association between glaucoma susceptibility with combined defects in mitochondrial oxidative phosphorylation and fatty acid beta oxidation","authors":"Zulvikar Syambani Ulhaq ,&nbsp;Guido Barbieri Bittencourt ,&nbsp;Gita Vita Soraya ,&nbsp;Lola Ayu Istifiani ,&nbsp;Syafrizal Aji Pamungkas ,&nbsp;Yukiko Ogino ,&nbsp;Dian Kesumapramudya Nurputra ,&nbsp;William Ka Fai Tse","doi":"10.1016/j.mam.2023.101238","DOIUrl":"https://doi.org/10.1016/j.mam.2023.101238","url":null,"abstract":"<div><p><span><span>Glaucoma is one of the leading causes of visual impairment and blindness worldwide, and is characterized by the progressive damage of retinal ganglion cells (RGCs) and the atrophy of the optic nerve head (ONH). The exact cause of RGC loss and optic nerve damage in glaucoma is not fully understood. The high energy demands of these cells imply a higher sensitivity to mitochondrial defects. Moreover, it has been postulated that the optic nerve is vulnerable towards damage from oxidative stress and mitochondrial dysfunction. To investigate this further, we conducted a pooled analysis of mitochondrial variants related to energy production, specifically focusing on </span>oxidative phosphorylation (OXPHOS) and fatty acid β-oxidation (FAO). Our findings revealed that patients carrying non-synonymous (NS) mitochondrial DNA (mtDNA) variants within the OXPHOS complexes had an almost two-fold increased risk of developing glaucoma. Regarding FAO, our results demonstrated that longer-chain acylcarnitines (AC) tended to decrease, while shorter-chain AC tended to increase in patients with glaucoma. Furthermore, we observed that the knocking down </span><em>cpt1a</em><span><span> (a key rate-limiting enzyme involved in FAO) in zebrafish induced a degenerative process in the optic nerve and RGC, which resembled the characteristics observed in glaucoma. In conclusion, our study provides evidence that genes encoding </span>mitochondrial proteins involved in energy metabolisms, such as OXPHOS and FAO, are associated with glaucoma. These findings contribute to a better understanding of the molecular mechanisms underlying glaucoma pathogenesis and may offer potential targets for therapeutic interventions in the future.</span></p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"96 ","pages":"Article 101238"},"PeriodicalIF":10.6,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139419122","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":"Introductory remarks","authors":"Diego Sbardella,&nbsp;Francesco Oddone,&nbsp;Massimiliano Coletta","doi":"10.1016/j.mam.2023.101241","DOIUrl":"10.1016/j.mam.2023.101241","url":null,"abstract":"","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"95 ","pages":"Article 101241"},"PeriodicalIF":10.6,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089194","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":"Corrigendum to “The changing epidemiology of fungal infections” [Mol. Aspect. Med. 94 (2023) 101215]","authors":"Cornelia Lass-Flörl,&nbsp;Stephan Steixner","doi":"10.1016/j.mam.2023.101240","DOIUrl":"10.1016/j.mam.2023.101240","url":null,"abstract":"","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"95 ","pages":"Article 101240"},"PeriodicalIF":10.6,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0098299723000808/pdfft?md5=829045d11e1f221aba42c344beafa4c2&pid=1-s2.0-S0098299723000808-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139058929","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":"Reviewing the significance of dendritic cell vaccines in interrupting breast cancer development","authors":"Namrata Gautam ,&nbsp;Ganesan Ramamoorthi ,&nbsp;Nicholas Champion ,&nbsp;Hyo S. Han ,&nbsp;Brian J. Czerniecki","doi":"10.1016/j.mam.2023.101239","DOIUrl":"10.1016/j.mam.2023.101239","url":null,"abstract":"<div><p>Breast cancer is a heterogeneous disease and is the most prevalent cancer in women. According to the U.S breast cancer statistics, about 1 in every 8 women develop an invasive form of breast cancer during their lifetime. Immunotherapy has been a significant advancement in the treatment of cancer with multiple studies reporting favourable patient outcomes by modulating the immune response to cancer cells. Here, we review the significance of dendritic cell vaccines in treating breast cancer patients. We discuss the involvement of dendritic cells and oncodrivers in breast tumorigenesis, highlighting the rationale for targeting oncodrivers and neoantigens using dendritic cell vaccine therapy. We review different dendritic cell subsets and maturation states previously used to develop vaccines and suggest the use of DC vaccines for breast cancer prevention. Further, we highlight that the intratumoral delivery of type 1 dendritic cell vaccines in breast cancer patients activates tumor antigen-specific CD4⁺<span> T helper cell type 1 (Th1) cells, promoting an anti-tumorigenic immune response while concurrently blocking pro-tumorigenic responses. In summary, this review provides an overview of the current state of dendritic cell vaccines in breast cancer highlighting the challenges and considerations necessary for an efficient dendritic cell vaccine design in interrupting breast cancer development.</span></p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"95 ","pages":"Article 101239"},"PeriodicalIF":10.6,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139049663","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":"Invited review liver fibrosis in NAFLD/NASH: From pathophysiology towards diagnostic and therapeutic strategies","authors":"Maurizio Parola ,&nbsp;Massimo Pinzani","doi":"10.1016/j.mam.2023.101231","DOIUrl":"https://doi.org/10.1016/j.mam.2023.101231","url":null,"abstract":"<div><p>Liver fibrosis, as an excess deposition of extracellular matrix (ECM) components, results from chronic liver injury as well as persistent activation of inflammatory response and of fibrogenesis. Liver fibrosis is a major determinant for chronic liver disease (CLD) progression and in the last two decades our understanding on the major molecular and cellular mechanisms underlying the fibrogenic progression of CLD has dramatically improved, boosting pre-clinical studies and clinical trials designed to find novel therapeutic approaches. From these studies several critical concepts have emerged, starting to reveal the complexity of the pro-fibrotic microenvironment which involves very complex, dynamic and interrelated interactions between different hepatic and extrahepatic cell populations. This review will offer first a recapitulation of established and novel pathophysiological basic principles and concepts by intentionally focus the attention on NAFLD/NASH, a metabolic-related form of CLD with a high impact on the general population and emerging as a leading cause of CLD worldwide. NAFLD/NASH-related pro-inflammatory and profibrogenic mechanisms will be analysed as well as novel information on cells, mediators and signalling pathways which have taken advantage from novel methodological approaches and techniques (single cell genomics, imaging mass cytometry, novel in vitro two- and three-dimensional models, etc.). We will next offer an overview on recent advancement in diagnostic and prognostic tools, including serum biomarkers and polygenic scores, to support the analysis of liver biopsies. Finally, this review will provide an analysis of current and emerging therapies for the treatment of NAFLD/NASH patients.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"95 ","pages":"Article 101231"},"PeriodicalIF":10.6,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0098299723000717/pdfft?md5=e6df0e51adb7874e0c1c50e189d9d68b&pid=1-s2.0-S0098299723000717-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138489784","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":"Rodent genetically modified models of glaucoma","authors":"Yunhua Loo ,&nbsp;Anita Sook Yee Chan ,&nbsp;Chiea Chuen Khor ,&nbsp;Tin Aung ,&nbsp;Zhenxun Wang","doi":"10.1016/j.mam.2023.101229","DOIUrl":"https://doi.org/10.1016/j.mam.2023.101229","url":null,"abstract":"<div><p><span>Glaucoma, one of the leading causes of irreversible blindness worldwide, is a complex and heterogenous disease. While environmental factors are important, it is well-recognized that the disease has a strong heritable component. With the advent of large-cohort genome wide association studies, a myriad of genetic risk loci has been linked to different forms of glaucoma. </span>Animal models have been an indispensable tool in characterizing these loci, especially if they lie within coding regions in the genome. Not only do these models connect genotype to phenotype, advancing our understanding of glaucoma pathogenesis in the process, they also have valuable utility as a platform for the pre-clinical testing of potential therapies. In this review, we will outline genetic models used for studying the major forms of glaucoma, including primary open angle glaucoma, normal tension glaucoma, primary angle closure glaucoma, pigmentary glaucoma, pseudoexfoliation glaucoma, and early onset glaucoma, including congenital and developmental glaucoma, and how studying these models have helped shed light on human glaucoma.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"95 ","pages":"Article 101229"},"PeriodicalIF":10.6,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138467536","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":"Genetic rodent models of glaucoma in representing disease phenotype and insights into the pathogenesis","authors":"Renu Agarwal,&nbsp;Igor Iezhitsa","doi":"10.1016/j.mam.2023.101228","DOIUrl":"https://doi.org/10.1016/j.mam.2023.101228","url":null,"abstract":"<div><p><span><span>Genetic rodent models are widely used in glaucoma related research. With vast amount of information revealed by human studies about genetic correlations with glaucoma, use of these models is relevant and required. In this review, we discuss the glaucoma </span>endophenotypes<span> and importance of their representation in an experimental animal model. Mice and rats are the most popular animal species used as genetic models due to ease of genetic manipulations in these animal species as well as the availability of their genomic information. With technological advances, induction of glaucoma related </span></span>genetic mutations<span><span> commonly observed in human is possible to achieve in rodents in a desirable manner. This approach helps to study the pathobiology of the disease process with the background of genetic abnormalities, reveals potential therapeutic targets and gives an opportunity to test newer therapeutic options. Various genetic manipulation leading to appearance of human relevant endophenotypes in rodents indicate their relevance in glaucoma pathology and the utility of these rodent models for exploring various aspects of the disease related to targeted mutation. The molecular pathways involved in the pathophysiology of glaucoma leading to elevated intraocular pressure and the disease hallmark, apoptosis of retinal ganglion cells and optic nerve degeneration, have been extensively explored in genetic rodent models. In this review, we discuss the consequences of various genetic manipulations based on the primary site of pathology in the anterior or the posterior segment. We discuss how these genetic manipulations produce features in rodents that can be considered a close representation of disease phenotype in human. We also highlight several molecular mechanisms revealed by using genetic rodent models of glaucoma including those involved in increased </span>aqueous outflow resistance, loss of retinal ganglion cells and optic neuropathy. Lastly, we discuss the limitations of the use of genetic rodent models in glaucoma related research.</span></p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"94 ","pages":"Article 101228"},"PeriodicalIF":10.6,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138448046","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":"Practical issues related to non-Aspergillus invasive mold infections","authors":"Marcio Nucci ,&nbsp;Simone A. Nouér","doi":"10.1016/j.mam.2023.101230","DOIUrl":"https://doi.org/10.1016/j.mam.2023.101230","url":null,"abstract":"<div><p>Infection by non-<span><em>Aspergillus</em></span><span><span> molds has been increasingly reported. The management of such infections is challenging both for diagnosis and treatment, including the need of well-trained mycologists to properly identify rare fungi, difficulties in distinguishing between contamination, colonization and infection, the lack of randomized studies comparing different drugs or regimens, poor activity of available antifungal agents, lack of correlation between in vitro </span>antifungal susceptibility tests and clinical outcome, and poor prognosis. Mucormycosis and fusariosis are the most frequent non-</span><em>Aspergillus</em><span> mold infections. Mucormycosis occurs more frequently in four major groups of patients: solid organ transplant recipients, patients with hematologic malignancies receiving chemotherapy or hematopoietic cell transplantation, diabetic patients, and immunocompetent individuals who suffer various types of skin and soft tissue trauma. Invasive fusariosis occurs almost exclusively in patients with hematologic malignancies. In this review we discuss practical issues related to the management of these and other non-</span><em>Aspergillus</em> mold infections.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"94 ","pages":"Article 101230"},"PeriodicalIF":10.6,"publicationDate":"2023-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138439145","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":"Novel frontiers in neuroprotective therapies in glaucoma: Molecular and clinical aspects","authors":"Alessandra Boccaccini ,&nbsp;Dario Cavaterra ,&nbsp;Carmela Carnevale ,&nbsp;Lucia Tanga ,&nbsp;Stefano Marini ,&nbsp;Alessio Bocedi ,&nbsp;Pedro M. Lacal ,&nbsp;Gianluca Manni ,&nbsp;Grazia Graziani ,&nbsp;Diego Sbardella ,&nbsp;Grazia Raffaella Tundo","doi":"10.1016/j.mam.2023.101225","DOIUrl":"https://doi.org/10.1016/j.mam.2023.101225","url":null,"abstract":"<div><p><span>In the last years, neuroprotective therapies have attracted the researcher interests as modern and challenging approach for the treatment of neurodegenerative diseases, aimed at protecting the nervous system from injuries. Glaucoma is a neurodegenerative disease characterized by progressive excavation of the optic nerve head, retinal axonal injury and corresponding vision loss that affects millions of people on a global scale. The molecular basis of the pathology is largely uncharacterized yet, and the therapeutic approaches available do not change the natural course of the disease. Therefore, in accordance with the therapeutic regimens proposed for other neurodegenerative diseases, a modern strategy to treat glaucoma includes prescription of drugs with neuroprotective activities. With respect to this, several preclinical and clinical investigations on a plethora of different drugs are currently ongoing. In this review, first, the conceptualization of the rationale for the adoption of neuroprotective strategies for retina is summarized. Second, the molecular aspects highlighting glaucoma as a neurodegenerative disease are reported. In conclusion, the molecular and pharmacological properties of most promising direct neuroprotective drugs used to delay glaucoma progression are examined, including: neurotrophic factors, NMDA </span>receptor antagonists<span><span><span>, the α2-adrenergic agonist, brimonidine, </span>calcium channel blockers, antioxidant agents, </span>nicotinamide and statins.</span></p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"94 ","pages":"Article 101225"},"PeriodicalIF":10.6,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138413163","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":"Pulmonary fibrosis: Emerging diagnostic and therapeutic strategies","authors":"Brintha Selvarajah ,&nbsp;Manuela Platé ,&nbsp;Rachel C. Chambers","doi":"10.1016/j.mam.2023.101227","DOIUrl":"https://doi.org/10.1016/j.mam.2023.101227","url":null,"abstract":"<div><p>Fibrosis is the concluding pathological outcome and major cause of morbidity and mortality in a number of common chronic inflammatory, immune-mediated and metabolic diseases. The progressive deposition of a collagen-rich extracellular matrix (ECM) represents the cornerstone of the fibrotic response and culminates in organ failure and premature death. Idiopathic pulmonary fibrosis (IPF) represents the most rapidly progressive and lethal of all fibrotic diseases with a dismal median survival of 3.5 years from diagnosis. Although the approval of the antifibrotic agents, pirfenidone and nintedanib, for the treatment of IPF signalled a watershed moment for the development of anti-fibrotic therapeutics, these agents slow but do not halt disease progression or improve quality of life. There therefore remains a pressing need for the development of effective therapeutic strategies. In this article, we review emerging therapeutic strategies for IPF as well as the pre-clinical and translational approaches that will underpin a greater understanding of the key pathomechanisms involved in order to transform the way we diagnose and treat pulmonary fibrosis.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"94 ","pages":"Article 101227"},"PeriodicalIF":10.6,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138413164","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}