WIREs Mechanisms of Disease最新文献_第5页

Advances in biomarker discovery using circulating cell-free DNA for early detection of hepatocellular carcinoma. 利用循环无细胞 DNA 发现生物标记物以早期检测肝细胞癌的进展。

IF 3.1 3区医学

WIREs Mechanisms of Disease Pub Date : 2023-05-01 Epub Date: 2023-01-25 DOI: 10.1002/wsbm.1598

Mingjun Liu, Zhou Zhang, Wei Zhang, Song-Mei Liu

{"title":"Advances in biomarker discovery using circulating cell-free DNA for early detection of hepatocellular carcinoma.","authors":"Mingjun Liu, Zhou Zhang, Wei Zhang, Song-Mei Liu","doi":"10.1002/wsbm.1598","DOIUrl":"10.1002/wsbm.1598","url":null,"abstract":"The past several decades have witnessed unprecedented progress in basic and clinical cancer research, and our understanding of the molecular mechanisms and pathogenesis of cancers have been greatly improved. More recently, with the availability of high-throughput sequencing and profiling platforms as well as sophisticated analytical tools and high-performance computing capacity, there have been tremendous advances in the development of diagnostic approaches in clinical oncology, especially the discovery of novel biomarkers for cancer early detection. Although tissue biopsy-based pathology has been the \"gold standard\" for cancer diagnosis, notable limitations such as the risk due to invasiveness and the bias due to intra-tumoral heterogeneity have limited its broader applications in oncology (e.g., screening, regular disease monitoring). Liquid biopsy analysis that exploits the genetic and epigenetic information contained in DNA/RNA materials from body fluids, particularly circulating cell-free DNA (cfDNA) in the blood, has been an intriguing alternative approach because of advantageous features such as sampling convenience and minimal invasiveness. Taking advantage of innovative enabling technologies, cfDNA has been demonstrated for its clinical potential in cancer early detection, including hepatocellular carcinoma (HCC), the most common liver cancer that causes serious healthcare burden globally. Hereby, we reviewed the current advances in cfDNA-based approaches for cancer biomarker discovery, with a focus on recent findings of cfDNA-based early detection of HCC. Future clinical investigations and trials are warranted to further validate these approaches for early detection of HCC, which will contribute to more effective prevention, control, and intervention strategies with the ultimate goal of reducing HCC-associated mortality. This article is categorized under: Cancer > Genetics/Genomics/Epigenetics.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"15 3","pages":"e1598"},"PeriodicalIF":3.1,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10176863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9679727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intracellular and microenvironmental regulation of mitochondrial membrane potential in cancer cells. 癌细胞线粒体膜电位的胞内和微环境调控。

IF 3.1 3区医学

WIREs Mechanisms of Disease Pub Date : 2023-05-01 Epub Date: 2023-01-03 DOI: 10.1002/wsbm.1595

Hydari Masuma Begum, Keyue Shen

{"title":"Intracellular and microenvironmental regulation of mitochondrial membrane potential in cancer cells.","authors":"Hydari Masuma Begum, Keyue Shen","doi":"10.1002/wsbm.1595","DOIUrl":"10.1002/wsbm.1595","url":null,"abstract":"Cancer cells have an abnormally high mitochondrial membrane potential (ΔΨm ), which is associated with enhanced invasive properties in vitro and increased metastases in vivo. The mechanisms underlying the abnormal ΔΨm in cancer cells remain unclear. Research on different cell types has shown that ΔΨm is regulated by various intracellular mechanisms such as by mitochondrial inner and outer membrane ion transporters, cytoskeletal elements, and biochemical signaling pathways. On the other hand, the role of extrinsic, tumor microenvironment (TME) derived cues in regulating ΔΨm is not well defined. In this review, we first summarize the existing literature on intercellular mechanisms of ΔΨm regulation, with a focus on cancer cells. We then offer our perspective on the different ways through which the microenvironmental cues such as hypoxia and mechanical stresses may regulate cancer cell ΔΨm . This article is categorized under: Cancer > Environmental Factors Cancer > Biomedical Engineering Cancer > Molecular and Cellular Physiology.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"15 3","pages":"e1595"},"PeriodicalIF":3.1,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10176868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9735174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In vitro maturation of oocytes as a laboratory approach to polycystic ovarian syndrome (PCOS): From oocyte to embryo. 卵母细胞体外成熟是治疗多囊卵巢综合征（PCOS）的一种实验室方法：从卵母细胞到胚胎。

IF 3.1 3区医学

WIREs Mechanisms of Disease Pub Date : 2023-05-01 Epub Date: 2023-02-13 DOI: 10.1002/wsbm.1600

Patricia Rodrigues, Monica Marques, Juan Aibar Manero, Maria D Marujo, Maria José Carvalho, Carlos E Plancha

{"title":"In vitro maturation of oocytes as a laboratory approach to polycystic ovarian syndrome (PCOS): From oocyte to embryo.","authors":"Patricia Rodrigues, Monica Marques, Juan Aibar Manero, Maria D Marujo, Maria José Carvalho, Carlos E Plancha","doi":"10.1002/wsbm.1600","DOIUrl":"10.1002/wsbm.1600","url":null,"abstract":"Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age, which in some case leads to infertility. This disorder is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Infertile PCOS women that need in vitro fertilization (IVF) have greater risk of ovarian hyperstimulation syndrome (OHSS) if conventional ovarian stimulation is used. In vitro oocyte maturation (IVM) is an alternative technique that prevents OHSS in infertile PCOS women. In the last decade, IVM protocols have improved, particularly with the development of biphasic IVM culture accounting for better pregnancy and live birth rates. This technique has been extended to other treatments like, fertility preservation, when patients have no time, or a contra-indication for ovarian stimulation, and poor responders. In this review, we will discuss IVM as a viable option for PCOS infertile patients. This article is categorized under: Reproductive System Diseases > Molecular and Cellular Physiology Reproductive System Diseases > Environmental Factors Reproductive System Diseases > Genetics/Genomics/Epigenetics.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"15 3","pages":"e1600"},"PeriodicalIF":3.1,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10055629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interleukin-17 as a spatiotemporal bridge from acute to chronic inflammation: Novel insights from computational modeling. 白细胞介素-17 作为从急性炎症到慢性炎症的时空桥梁：来自计算模型的新见解。

IF 3.1 3区医学

WIREs Mechanisms of Disease Pub Date : 2023-05-01 Epub Date: 2023-01-29 DOI: 10.1002/wsbm.1599

Ashti M Shah, Ruben Zamora, Yoram Vodovotz

{"title":"Interleukin-17 as a spatiotemporal bridge from acute to chronic inflammation: Novel insights from computational modeling.","authors":"Ashti M Shah, Ruben Zamora, Yoram Vodovotz","doi":"10.1002/wsbm.1599","DOIUrl":"10.1002/wsbm.1599","url":null,"abstract":"A systematic review of several acute inflammatory diseases ranging from sepsis and trauma/hemorrhagic shock to the relevant pathology of the decade, COVID-19, points to the cytokine interleukin (IL)-17A as being centrally involved in the propagation of inflammation. We summarize the role of IL-17A in acute inflammation, leveraging insights made possible by biological network analysis and novel computational methodologies aimed at defining the spatiotemporal spread of inflammation in both experimental animal models and humans. These studies implicate IL-17A in the cross-tissue spread of inflammation, a process that appears to be in part regulated through neural mechanisms. Although acute inflammatory diseases are currently considered distinct from chronic inflammatory pathologies, we suggest that chronic inflammation may represent repeated, cyclical episodes of acute inflammation driven by mechanisms involving IL-17A. Thus, insights from computational modeling of acute inflammatory diseases may improve diagnosis and treatment of chronic inflammation; in turn, therapeutics developed for chronic/autoimmune disease may be of benefit in acute inflammation. This article is categorized under: Immune System Diseases > Computational Models.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"15 3","pages":"e1599"},"PeriodicalIF":3.1,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10176872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10038078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cover Image, Volume 15, Issue 2 封面图片，第15卷，第2期

IF 3.1 3区医学

WIREs Mechanisms of Disease Pub Date : 2023-03-14 DOI: 10.1002/wsbm.1605

引用次数: 0

Human globozoospermia-related genes and their role in acrosome biogenesis. 人类球形精子症相关基因及其在顶体生物发生中的作用。

IF 3.1 3区医学

WIREs Mechanisms of Disease Pub Date : 2023-03-01 DOI: 10.1002/wsbm.1589

Ricardo D Moreno

{"title":"Human globozoospermia-related genes and their role in acrosome biogenesis.","authors":"Ricardo D Moreno","doi":"10.1002/wsbm.1589","DOIUrl":"https://doi.org/10.1002/wsbm.1589","url":null,"abstract":"The mammalian acrosome is a secretory vesicle attached to the sperm nucleus whose fusion with the overlying plasma membrane is required to achieve fertilization. Acrosome biogenesis starts during meiosis, but it lasts through the entire process of haploid cell differentiation (spermiogenesis). Acrosome biogenesis is a stepwise process that involves membrane traffic from the Golgi apparatus, but it also seems that the lysosome/endosome system participates in this process. Defective sperm head morphology is accompanied by defective acrosome shape and function, and patients with these characteristics are infertile or subfertile. The most extreme case of acrosome biogenesis failure is globozoospermia syndrome, which is primarily characterized by the presence of round-headed spermatozoa without acrosomes with cytoskeleton defects around the nucleus and infertility. Several genes participating in acrosome biogenesis have been uncovered using genetic deletions in mice, but only a few of them have been found to be deleted or modified in patients with globozoospermia. Understanding acrosome biogenesis is crucial to uncovering the molecular basis of male infertility and developing new diagnostic tools and assisted reproductive technologies that may help infertile patients through more effective treatment techniques. This article is categorized under: Reproductive System Diseases > Environmental Factors Infectious Diseases > Stem Cells and Development Reproductive System Diseases > Molecular and Cellular Physiology.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"15 2","pages":"e1589"},"PeriodicalIF":3.1,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9694169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Pathogenesis mechanisms of phytopathogen effectors. 植物病原菌效应物的发病机制。

IF 3.1 3区医学

WIREs Mechanisms of Disease Pub Date : 2023-03-01 DOI: 10.1002/wsbm.1592

Lifan Sun, Xiaoyun Wu, Jian Diao, Jie Zhang

引用次数: 0

Perspectives on optimizing local delivery of drugs to peripheral nerves using mathematical models. 利用数学模型优化外周神经局部给药的视角。

IF 4.6 3区医学

WIREs Mechanisms of Disease Pub Date : 2023-03-01 Epub Date: 2023-01-09 DOI: 10.1002/wsbm.1593

Simao Laranjeira, Victoria H Roberton, James B Phillips, Rebecca J Shipley

{"title":"Perspectives on optimizing local delivery of drugs to peripheral nerves using mathematical models.","authors":"Simao Laranjeira, Victoria H Roberton, James B Phillips, Rebecca J Shipley","doi":"10.1002/wsbm.1593","DOIUrl":"10.1002/wsbm.1593","url":null,"abstract":"Drug therapies for treating peripheral nerve injury repair have shown significant promise in preclinical studies. Despite this, drug treatments are not used routinely clinically to treat patients with peripheral nerve injuries. Drugs delivered systemically are often associated with adverse effects to other tissues and organs; it remains challenging to predict the effective concentration needed at an injured nerve and the appropriate delivery strategy. Local drug delivery approaches are being developed to mitigate this, for example via injections or biomaterial-mediated release. We propose the integration of mathematical modeling into the development of local drug delivery protocols for peripheral nerve injury repair. Mathematical models have the potential to inform understanding of the different transport mechanisms at play, as well as quantitative predictions around the efficacy of individual local delivery protocols. We discuss existing approaches in the literature, including drawing from other research fields, and present a process for taking forward an integrated mathematical-experimental approach to accelerate local drug delivery approaches for peripheral nerve injury repair. This article is categorized under: Neurological Diseases > Molecular and Cellular Physiology Neurological Diseases > Computational Models Neurological Diseases > Biomedical Engineering.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"15 2","pages":"e1593"},"PeriodicalIF":4.6,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10909486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9325048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Insights into the sperm chromatin and implications for male infertility from a protein perspective. 从蛋白质的角度深入了解精子染色质及其对男性不育的影响。

IF 3.1 3区医学

WIREs Mechanisms of Disease Pub Date : 2023-03-01 DOI: 10.1002/wsbm.1588

Alberto de la Iglesia, Meritxell Jodar, Rafael Oliva, Judit Castillo

{"title":"Insights into the sperm chromatin and implications for male infertility from a protein perspective.","authors":"Alberto de la Iglesia, Meritxell Jodar, Rafael Oliva, Judit Castillo","doi":"10.1002/wsbm.1588","DOIUrl":"https://doi.org/10.1002/wsbm.1588","url":null,"abstract":"Male germ cells undergo an extreme but fascinating process of chromatin remodeling that begins in the testis during the last phase of spermatogenesis and continues through epididymal sperm maturation. Most of the histones are replaced by small proteins named protamines, whose high basicity leads to a tight genomic compaction. This process is epigenetically regulated at many levels, not only by posttranslational modifications, but also by readers, writers, and erasers, in a context of a highly coordinated postmeiotic gene expression program. Protamines are key proteins for acquiring this highly specialized chromatin conformation, needed for sperm functionality. Interestingly, and contrary to what could be inferred from its very specific DNA-packaging function across protamine-containing species, human sperm chromatin contains a wide spectrum of protamine proteoforms, including truncated and posttranslationally modified proteoforms. The generation of protamine knock-out models revealed not only chromatin compaction defects, but also collateral sperm alterations contributing to infertile phenotypes, evidencing the importance of sperm chromatin protamination toward the generation of a new individual. The unique features of sperm chromatin have motivated its study, applying from conventional to the most ground-breaking techniques to disentangle its peculiarities and the cellular mechanisms governing its successful conferment, especially relevant from the protein point of view due to the important epigenetic role of sperm nuclear proteins. Gathering and contextualizing the most striking discoveries will provide a global understanding of the importance and complexity of achieving a proper chromatin compaction and exploring its implications on postfertilization events and beyond. This article is categorized under: Reproductive System Diseases > Genetics/Genomics/Epigenetics Reproductive System Diseases > Molecular and Cellular Physiology.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"15 2","pages":"e1588"},"PeriodicalIF":3.1,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9680012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Beyond the classical amyloid hypothesis in Alzheimer's disease: Molecular insights into current concepts of pathogenesis, therapeutic targets, and study models. 超越阿尔茨海默病的经典淀粉样蛋白假说:对当前发病机制、治疗靶点和研究模型概念的分子见解。

IF 3.1 3区医学

WIREs Mechanisms of Disease Pub Date : 2023-03-01 DOI: 10.1002/wsbm.1591

Atsadang Theerasri, Sakawrat Janpaijit, Tewin Tencomnao, Anchalee Prasansuklab

{"title":"Beyond the classical amyloid hypothesis in Alzheimer's disease: Molecular insights into current concepts of pathogenesis, therapeutic targets, and study models.","authors":"Atsadang Theerasri, Sakawrat Janpaijit, Tewin Tencomnao, Anchalee Prasansuklab","doi":"10.1002/wsbm.1591","DOIUrl":"https://doi.org/10.1002/wsbm.1591","url":null,"abstract":"Alzheimer's disease (AD) is one of the progressive neurodegenerative disorders and the most common cause of dementia in the elderly worldwide causing difficulties in the daily life of the patient. AD is characterized by the aberrant accumulation of β-amyloid plaques and tau protein-containing neurofibrillary tangles (NFTs) in the brain giving rise to neuroinflammation, oxidative stress, synaptic failure, and eventual neuronal cell death. The total cost of care in AD treatment and related health care activities is enormous and pharmaceutical drugs approved by Food and Drug Administration have not manifested sufficient efficacy in protection and therapy. In recent years, there are growing studies that contribute a fundamental understanding to AD pathogenesis, AD-associated risk factors, and pharmacological intervention. However, greater molecular process-oriented research in company with suitable experimental models is still of the essence to enhance the prospects for AD therapy and cell lines as a disease model are still the major part of this milestone. In this review, we provide an insight into molecular mechanisms, particularly the recent concept in gut-brain axis, vascular dysfunction and autophagy, and current models used in the study of AD. Here, we emphasized the importance of therapeutic strategy targeting multiple mechanisms together with utilizing appropriate models for the discovery of novel effective AD therapy. This article is categorized under: Neurological Diseases > Molecular and Cellular Physiology.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"15 2","pages":"e1591"},"PeriodicalIF":3.1,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9680022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3