Molecular Aspects of Medicine最新文献

{"title":"Digital PCR for the characterization of reference materials","authors":"Megan H. Cleveland ,&nbsp;Hua-Jun He ,&nbsp;Mojca Milavec ,&nbsp;Young-Kyung Bae ,&nbsp;Peter M. Vallone ,&nbsp;Jim F. Huggett","doi":"10.1016/j.mam.2024.101256","DOIUrl":"https://doi.org/10.1016/j.mam.2024.101256","url":null,"abstract":"<div><p>Well-characterized reference materials support harmonization and accuracy when conducting nucleic acid-based tests (such as qPCR); digital PCR (dPCR) can measure the absolute concentration of a specific nucleic acid sequence in a background of non-target sequences, making it ideal for the characterization of nucleic acid-based reference materials. National Metrology Institutes are increasingly using dPCR to characterize and certify their reference materials, as it offers several advantages over indirect methods, such as UV-spectroscopy. While dPCR is gaining widespread adoption, it requires optimization and has certain limitations and considerations that users should be aware of when characterizing reference materials. This review highlights the technical considerations of dPCR, as well as its role when developing and characterizing nucleic acid-based reference materials.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"96 ","pages":"Article 101256"},"PeriodicalIF":10.6,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0098299724000153/pdfft?md5=5a0566fe58b8e85a0d28442f6e8e36f5&pid=1-s2.0-S0098299724000153-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139738777","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":"Are we getting closer to a successful neoantigen cancer vaccine?","authors":"Karen Manoutcharian ,&nbsp;Goar Gevorkian","doi":"10.1016/j.mam.2024.101254","DOIUrl":"https://doi.org/10.1016/j.mam.2024.101254","url":null,"abstract":"<div><p>Although significant advances in immunotherapy have revolutionized the treatment of many cancer types over the past decade, the field of vaccine therapy, an important component of cancer immunotherapy, despite decades-long intense efforts, is still transmitting signals of promises and awaiting strong data on efficacy to proceed with regulatory approval. The field of cancer vaccines faces standard challenges, such as tumor-induced immunosuppression, immune response in inhibitory tumor microenvironment (TME), intratumor heterogeneity (ITH), permanently evolving cancer mutational landscape leading to neoantigens, and less known obstacles: neoantigen gain/loss upon immunotherapy, the timing and speed of appearance of neoantigens and responding T cell clonotypes and possible involvement of immune interference/heterologous immunity, in the complex interplay between evolving tumor epitopes and the immune system. In this review, we discuss some key issues related to challenges hampering the development of cancer vaccines, along with the current approaches focusing on neoantigens. We summarize currently well-known ideas/rationales, thus revealing the need for alternative vaccine approaches. Such a discussion should stimulate vaccine researchers to apply out-of-box, unconventional thinking in search of new avenues to deal with critical, often yet unaddressed challenges on the road to a new generation of therapeutics and vaccines.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"96 ","pages":"Article 101254"},"PeriodicalIF":10.6,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139726127","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":"Current and emerging sequencing-based tools for precision cancer medicine","authors":"Anders Edsjö ,&nbsp;David Gisselsson ,&nbsp;Johan Staaf ,&nbsp;Louise Holmquist ,&nbsp;Thoas Fioretos ,&nbsp;Lucia Cavelier ,&nbsp;Richard Rosenquist","doi":"10.1016/j.mam.2024.101250","DOIUrl":"10.1016/j.mam.2024.101250","url":null,"abstract":"<div><p>Current precision cancer medicine is dependent on the analyses of a plethora of clinically relevant genomic aberrations. During the last decade, next-generation sequencing (NGS) has gradually replaced most other methods for precision cancer diagnostics, spanning from targeted tumor-informed assays and gene panel sequencing to global whole-genome and whole-transcriptome sequencing analyses. The shift has been impelled by a clinical need to assess an increasing number of genomic alterations with diagnostic, prognostic and predictive impact, including more complex biomarkers (e.g. microsatellite instability, MSI, and homologous recombination deficiency, HRD), driven by the parallel development of novel targeted therapies and enabled by the rapid reduction in sequencing costs. This review focuses on these sequencing-based methods, puts their emergence in a historic perspective, highlights their clinical utility in diagnostics and decision-making in pediatric and adult cancer, as well as raises challenges for their clinical implementation. Finally, the importance of applying sensitive tools for longitudinal monitoring of treatment response and detection of measurable residual disease, as well as future avenues in the rapidly evolving field of sequencing-based methods are discussed.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"96 ","pages":"Article 101250"},"PeriodicalIF":10.6,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139708381","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":"Emerging diagnostic and therapeutic challenges for skin fibrosis in systemic sclerosis","authors":"David Abraham ,&nbsp;Alain Lescoat ,&nbsp;Richard Stratton","doi":"10.1016/j.mam.2024.101252","DOIUrl":"https://doi.org/10.1016/j.mam.2024.101252","url":null,"abstract":"<div><p>Systemic sclerosis (also called scleroderma, SSc) is a chronic autoimmune disorder characterized by excessive collagen deposition leading to skin fibrosis and various internal organ manifestations. The emergent diagnostics and therapeutic strategies for scleroderma focus on early detection and targeted interventions to improve patient outcomes and quality of life. Diagnostics for SSc have evolved significantly in recent years, driven by advancements in serological markers and imaging techniques. Autoantibody profiling, especially antinuclear antibodies (ANA) and specific scleroderma-associated autoantibodies, aids in identifying subsets of scleroderma and predicting disease progression. Furthermore, novel imaging modalities, such as high-frequency ultrasonography and optical coherence tomography, enable early detection of skin fibrosis and internal organ involvement, enhancing the diagnostic precision and allowing for tailored management. Therapeutic strategies for SSc are multifaceted, targeting immune dysregulation, vascular abnormalities, and fibrotic processes. Emerging biologic agents have shown promise in clinical trials, including monoclonal antibodies directed against key cytokines involved in fibrosis, such as transforming growth factor-β (TGF-β) and interleukin-6 (IL-6). Additionally, small-molecule inhibitors that disrupt fibrotic pathways, like tyrosine kinase inhibitors, have exhibited potential in limiting collagen deposition and preventing disease progression. Stem cell therapy, cell ablation and gene editing techniques hold great potential in regenerating damaged tissue and halting fibrotic processes. Early intervention remains crucial in managing SSc, as irreversible tissue damage often occurs in advanced stages. Novel diagnostic methods, such as biomarkers and gene expression profiling, are being explored to identify individuals at high risk for developing progressive severe disease and intervene proactively. Furthermore, patient-tailored therapeutic approaches, employing a combination of immunosuppressive agents and targeted anti-fibrotic therapies, are being investigated to improve treatment efficacy while minimizing adverse effects. The emergent diagnostics and therapeutic strategies in scleroderma are transforming the management of this challenging disease. Nevertheless, ongoing research and clinical trials are needed to optimize the efficacy and safety of these novel approaches in the complex and diverse spectrum of SSc manifestations.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"96 ","pages":"Article 101252"},"PeriodicalIF":10.6,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0098299724000116/pdfft?md5=1b66a46eb14c6531e417ce904c91dfd4&pid=1-s2.0-S0098299724000116-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139694848","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":"Improving the quality of quantitative polymerase chain reaction experiments: 15 years of MIQE","authors":"Stephen A. Bustin","doi":"10.1016/j.mam.2024.101249","DOIUrl":"10.1016/j.mam.2024.101249","url":null,"abstract":"<div><p>The quantitative polymerase chain reaction (qPCR) is fundamental to molecular biology. It is not just a laboratory technique, qPCR is a bridge between research and clinical practice. Its theoretical foundations guide the design of experiments, while its practical implications extend to diagnostics, treatment, and research advancements in the life sciences, human and veterinary medicine, agriculture, and forensics. However, the accuracy, reliability and reproducibility of qPCR data face challenges arising from various factors associated with experimental design, execution, data analysis and inadequate reporting details. Addressing these concerns, the Minimum Information for the Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines have emerged as a cohesive framework offering a standardised set of recommendations that describe the essential information required for assessing qPCR experiments. By emphasising the importance of methodological rigour, the MIQE guidelines have made a major contribution to improving the trustworthiness, consistency, and transparency of many published qPCR results. However, major challenges related to awareness, resources, and publication pressures continue to affect their consistent application.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"96 ","pages":"Article 101249"},"PeriodicalIF":10.6,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0098299724000086/pdfft?md5=05d9e4a560791754847c55c60db27636&pid=1-s2.0-S0098299724000086-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139581029","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":"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}