Molecular Aspects of Medicine最新文献

{"title":"Frontiers in sarcopenia: Advancements in diagnostics, molecular mechanisms, and therapeutic strategies","authors":"Dequan Liu ,&nbsp;Shijin Wang ,&nbsp;Shuang Liu ,&nbsp;Qifei Wang,&nbsp;Xiangyu Che,&nbsp;Guangzhen Wu","doi":"10.1016/j.mam.2024.101270","DOIUrl":"https://doi.org/10.1016/j.mam.2024.101270","url":null,"abstract":"<div><p>The onset of sarcopenia is intimately linked with aging, posing significant implications not only for individual patient quality of life but also for the broader societal healthcare framework. Early and accurate identification of sarcopenia and a comprehensive understanding of its mechanistic underpinnings and therapeutic targets paramount to addressing this condition effectively. This review endeavors to present a cohesive overview of recent advancements in sarcopenia research and diagnosis. We initially delve into the contemporary diagnostic criteria, specifically referencing the European Working Group on Sarcopenia in Older People (EWGSOP) 2 and Asian Working Group on Sarcopenia (AWGS) 2019 benchmarks. Additionally, we elucidate comprehensive assessment techniques for muscle strength, quantity, and physical performance, highlighting tools such as grip strength, chair stand test, dual-energy X-ray Absorptiometry (DEXA), bioelectrical impedance analysis (BIA), gait speed, and short physical performance battery (SPPB), while also discussing their inherent advantages and limitations. Such diagnostic advancements pave the way for early identification and unequivocal diagnosis of sarcopenia. Proceeding further, we provide a deep-dive into sarcopenia's pathogenesis, offering a thorough examination of associated signaling pathways like the Myostatin, AMP-activated protein kinase (AMPK), insulin/IGF-1 Signaling (IIS), and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. Each pathway's role in sarcopenia mediation is detailed, underscoring potential therapeutic target avenues. From a mechanistic perspective, the review also underscores the pivotal role of mitochondrial dysfunction in sarcopenia, emphasizing elements such as mitochondrial oxidative overload, mitochondrial biogenesis, and mitophagy, and highlighting their therapeutic significance. At last, we capture recent strides made in sarcopenia treatment, ranging from nutritional and exercise interventions to potential pharmacological and supplementation strategies. In sum, this review meticulously synthesizes the latest scientific developments in sarcopenia, aiming to enhance diagnostic precision in clinical practice and provide comprehensive insights into refined mechanistic targets and innovative therapeutic interventions, ultimately contributing to optimized patient care and advancements in the field.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"97 ","pages":"Article 101270"},"PeriodicalIF":10.6,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0098299724000293/pdfft?md5=0e9c7ed46ddf4cd9b5d03e5e7a83c4d5&pid=1-s2.0-S0098299724000293-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140533652","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":"A pipeline for the development and analysis of extracellular vesicle-based transcriptomic biomarkers in molecular diagnostics","authors":"Christian Grätz ,&nbsp;Martina Schuster ,&nbsp;Florian Brandes ,&nbsp;Agnes S. Meidert ,&nbsp;Benedikt Kirchner ,&nbsp;Marlene Reithmair ,&nbsp;Gustav Schelling ,&nbsp;Michael W. Pfaffl","doi":"10.1016/j.mam.2024.101269","DOIUrl":"https://doi.org/10.1016/j.mam.2024.101269","url":null,"abstract":"<div><p>Extracellular vesicles are shed by every cell type and can be found in any biofluid. They contain different molecules that can be utilized as biomarkers, including several RNA species which they protect from degradation. Here, we present a pipeline for the development and analysis of extracellular vesicle-associated transcriptomic biomarkers that our group has successfully applied multiple times. We highlight the key steps of the pipeline and give particular emphasis to the necessary quality control checkpoints, which are linked to numerous available guidelines that should be considered along the workflow. Our pipeline starts with patient recruitment and continues with blood sampling and processing. The purification and characterization of extracellular vesicles is explained in detail, as well as the isolation and quality control of extracellular vesicle-associated RNA. We point out the possible pitfalls during library preparation and RNA sequencing and present multiple bioinformatic tools to pinpoint biomarker signature candidates from the sequencing data. Finally, considerations and pitfalls during the validation of the biomarker signature using RT-qPCR will be elaborated.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"97 ","pages":"Article 101269"},"PeriodicalIF":10.6,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0098299724000281/pdfft?md5=0a27467e224143fcfa525c791bc3d1b6&pid=1-s2.0-S0098299724000281-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320505","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":"DNA melting analysis","authors":"Carl T. Wittwer ,&nbsp;Andrew C. Hemmert ,&nbsp;Jana O. Kent ,&nbsp;Nick A. Rejali","doi":"10.1016/j.mam.2024.101268","DOIUrl":"https://doi.org/10.1016/j.mam.2024.101268","url":null,"abstract":"<div><p>Melting is a fundamental property of DNA that can be monitored by absorbance or fluorescence. PCR conveniently produces enough DNA to be directly monitored on real-time instruments with fluorescently labeled probes or dyes. Dyes monitor the entire PCR product, while probes focus on a specific locus within the amplicon. Advances in amplicon melting include high resolution instruments, saturating DNA dyes that better reveal multiple products, prediction programs for domain melting, barcode taxonomic identification, high speed microfluidic melting, and highly parallel digital melting. Most single base variants and small insertions or deletions can be genotyped by high resolution amplicon melting. High resolution melting also enables heterozygote scanning for any variant within a PCR product. A web application (uMelt, <span>http://www.dna-utah.org</span><svg><path></path></svg>) predicts amplicon melting curves with multiple domains, a useful tool for verifying intended products. Additional applications include methylation assessment, copy number determination and verification of sequence identity. When amplicon melting does not provide sufficient detail, unlabeled probes or snapback primers can be used instead of covalently labeled probes. DNA melting is a simple, inexpensive, and powerful tool with many research applications that is beginning to make its mark in clinical diagnostics.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"97 ","pages":"Article 101268"},"PeriodicalIF":10.6,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140134437","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-associated muscle weakness - From triggers to molecular mechanisms","authors":"Emily Shorter,&nbsp;Viktor Engman,&nbsp;Johanna T. Lanner","doi":"10.1016/j.mam.2024.101260","DOIUrl":"https://doi.org/10.1016/j.mam.2024.101260","url":null,"abstract":"<div><p>Skeletal muscle weakness is a debilitating consequence of many malignancies. Muscle weakness has a negative impact on both patient wellbeing and outcome in a range of cancer types and can be the result of loss of muscle mass (i.e. muscle atrophy, cachexia) and occur independently of muscle atrophy or cachexia. There are multiple cancer specific triggers that can initiate the progression of muscle weakness, including the malignancy itself and the tumour environment, as well as chemotherapy, radiotherapy and malnutrition. This can induce weakness via different routes: 1) impaired intrinsic capacity (i.e., contractile dysfunction and intramuscular impairments in excitation-contraction coupling or crossbridge cycling), 2) neuromuscular disconnection and/or 3) muscle atrophy. The mechanisms that underlie these pathways are a complex interplay of inflammation, autophagy, disrupted protein synthesis/degradation, and mitochondrial dysfunction.</p><p>The current lack of therapies to treat cancer-associated muscle weakness highlight the critical need for novel interventions (both pharmacological and non-pharmacological) and mechanistic insight. Moreover, most research in the field has placed emphasis on directly improving muscle mass to improve muscle strength. However, accumulating evidence suggests that loss of muscle function precedes atrophy. This review primarily focuses on cancer-associated muscle weakness, independent of cachexia, and provides a solid background on the underlying mechanisms, methodology, current interventions, gaps in knowledge, and limitations of research in the field. Moreover, we have performed a mini-systematic review of recent research into the mechanisms behind muscle weakness in specific cancer types, along with the main pathways implicated.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"97 ","pages":"Article 101260"},"PeriodicalIF":10.6,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0098299724000190/pdfft?md5=018e5de2d724aea9ee0fca5188ab4b66&pid=1-s2.0-S0098299724000190-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140052684","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":"E3 ubiquitin ligase WWP2 as a promising therapeutic target for diverse human diseases","authors":"Shilong You ,&nbsp;Jiaqi Xu ,&nbsp;Yushan Guo ,&nbsp;Xiaofan Guo ,&nbsp;Ying Zhang ,&nbsp;Naijin Zhang ,&nbsp;Guozhe Sun ,&nbsp;Yingxian Sun","doi":"10.1016/j.mam.2024.101257","DOIUrl":"https://doi.org/10.1016/j.mam.2024.101257","url":null,"abstract":"<div><p>Mammalian E3 ubiquitin ligases have emerged in recent years as critical regulators of cellular homeostasis due to their roles in targeting substrate proteins for ubiquitination and triggering subsequent downstream signals. In this review, we describe the multiple roles of WWP2, an E3 ubiquitin ligase with unique and important functions in regulating a wide range of biological processes, including DNA repair, gene expression, signal transduction, and cell-fate decisions. As such, WWP2 has evolved to play a key role in normal physiology and diseases, such as tumorigenesis, skeletal development and diseases, immune regulation, cardiovascular disease, and others. We attempt to provide an overview of the biochemical, physiological, and pathophysiological roles of WWP2, as well as open questions for future research, particularly in the context of putative therapeutic opportunities.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"96 ","pages":"Article 101257"},"PeriodicalIF":10.6,"publicationDate":"2024-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140014595","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":"Organ Fibrosis: Emerging diagnostic and therapeutic strategies","authors":"Maurizio Parola,&nbsp;Massimo Pinzani","doi":"10.1016/j.mam.2024.101259","DOIUrl":"10.1016/j.mam.2024.101259","url":null,"abstract":"","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"96 ","pages":"Article 101259"},"PeriodicalIF":10.6,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139984367","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":"Circulating tumor cells as liquid biopsy markers in cancer patients","authors":"Daniel J. Smit ,&nbsp;Klaus Pantel","doi":"10.1016/j.mam.2024.101258","DOIUrl":"10.1016/j.mam.2024.101258","url":null,"abstract":"<div><p>Over the past decade, novel methods for enrichment and identification of cancer cells circulating in the blood have been established. Blood-based detection of cancer cells and other tumor-associated products can be summarized under the term of Liquid Biopsy. Circulating tumor cells (CTCs) have been used for diagnosis, risk stratification and treatment selection as well as treatment monitoring in several studies over the past years, thus representing a valuable biomarker for cancer patients. A plethora of methods to enrich, detect and analyze CTCs has been established. In contrast to other liquid biopsy analytes (e.g. ctDNA), CTCs represent a viable analyte that provides a unique opportunity to understand the underlaying biology of cancer and the metastatic cascade on the molecular level. In this review, we provide an overview on the current methods used for enrichment, detection, molecular and functional characterization of CTCs.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"96 ","pages":"Article 101258"},"PeriodicalIF":10.6,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0098299724000177/pdfft?md5=7c2ce35ba2392784cac7128e91459549&pid=1-s2.0-S0098299724000177-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139922708","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":"Single-cell and spatial transcriptomics: Bridging current technologies with long-read sequencing","authors":"Chengwei Ulrika Yuan ,&nbsp;Fu Xiang Quah ,&nbsp;Martin Hemberg","doi":"10.1016/j.mam.2024.101255","DOIUrl":"https://doi.org/10.1016/j.mam.2024.101255","url":null,"abstract":"<div><p>Single-cell technologies have transformed biomedical research over the last decade, opening up new possibilities for understanding cellular heterogeneity, both at the genomic and transcriptomic level. In addition, more recent developments of spatial transcriptomics technologies have made it possible to profile cells in their tissue context. In parallel, there have been substantial advances in sequencing technologies, and the third generation of methods are able to produce reads that are tens of kilobases long, with error rates matching the second generation short reads. Long reads technologies make it possible to better map large genome rearrangements and quantify isoform specific abundances. This further improves our ability to characterize functionally relevant heterogeneity. Here, we show how researchers have begun to combine single-cell, spatial transcriptomics, and long-read technologies, and how this is resulting in powerful new approaches to profiling both the genome and the transcriptome. We discuss the achievements so far, and we highlight remaining challenges and opportunities.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"96 ","pages":"Article 101255"},"PeriodicalIF":10.6,"publicationDate":"2024-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139749634","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":"Principles of digital sequencing using unique molecular identifiers","authors":"Daniel Andersson ,&nbsp;Firaol Tamiru Kebede ,&nbsp;Mandy Escobar ,&nbsp;Tobias Österlund ,&nbsp;Anders Ståhlberg","doi":"10.1016/j.mam.2024.101253","DOIUrl":"https://doi.org/10.1016/j.mam.2024.101253","url":null,"abstract":"<div><p>Massively parallel sequencing technologies have long been used in both basic research and clinical routine. The recent introduction of digital sequencing has made previously challenging applications possible by significantly improving sensitivity and specificity to now allow detection of rare sequence variants, even at single molecule level. Digital sequencing utilizes unique molecular identifiers (UMIs) to minimize sequencing-induced errors and quantification biases. Here, we discuss the principles of UMIs and how they are used in digital sequencing. We outline the properties of different UMI types and the consequences of various UMI approaches in relation to experimental protocols and bioinformatics. Finally, we describe how digital sequencing can be applied in specific research fields, focusing on cancer management where it can be used in screening of asymptomatic individuals, diagnosis, treatment prediction, prognostication, monitoring treatment efficacy and early detection of treatment resistance as well as relapse.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"96 ","pages":"Article 101253"},"PeriodicalIF":10.6,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0098299724000128/pdfft?md5=2534f88aaff8de5c99cb0c47e14e9dee&pid=1-s2.0-S0098299724000128-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139743987","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":"Recent advances in intestinal fibrosis","authors":"Marco Vincenzo Lenti ,&nbsp;Giovanni Santacroce ,&nbsp;Giacomo Broglio,&nbsp;Carlo Maria Rossi,&nbsp;Antonio Di Sabatino","doi":"10.1016/j.mam.2024.101251","DOIUrl":"https://doi.org/10.1016/j.mam.2024.101251","url":null,"abstract":"<div><p>Despite many progresses have been made in the treatment of inflammatory bowel disease, especially due to the increasing number of effective therapies, the development of tissue fibrosis is a very common occurrence along the natural history of this condition. To a certain extent, fibrogenesis is a physiological and necessary process in all those conditions characterised by chronic inflammation. However, the excessive deposition of extracellular matrix within the bowel wall will end up in the formation of strictures, with the consequent need for surgery. A number of mechanisms have been described in this process, but some of them are not yet clear. For sure, the main trigger is the presence of a persistent inflammatory status within the mucosa, which in turn favours the occurrence of a pro-fibrogenic environment. Among the main key players, myofibroblasts, fibroblasts, immune cells, growth factors and cytokines must be mentioned. Although there are no available therapies able to target fibrosis, the only way to prevent it is by controlling inflammation. In this review, we summarize the state of art of the mechanisms involved in gut fibrogenesis, how to diagnose it, and which potential targets could be druggable to tackle fibrosis.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"96 ","pages":"Article 101251"},"PeriodicalIF":10.6,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139731679","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}