WIREs Mechanisms of Disease最新文献_第6页

Comparing RNA-sequencing datasets from astrocytes, oligodendrocytes, and microglia in multiple sclerosis identifies novel dysregulated genes relevant to inflammation and myelination. 比较多发性硬化症中星形胶质细胞、少突胶质细胞和小胶质细胞的rna测序数据集，发现了与炎症和髓鞘形成相关的新的失调基因。

IF 3.1 3区医学

WIREs Mechanisms of Disease Pub Date : 2023-03-01 DOI: 10.1002/wsbm.1594

Sienna S Drake, Aliyah Zaman, Tristan Simas, Alyson E Fournier

{"title":"Comparing RNA-sequencing datasets from astrocytes, oligodendrocytes, and microglia in multiple sclerosis identifies novel dysregulated genes relevant to inflammation and myelination.","authors":"Sienna S Drake, Aliyah Zaman, Tristan Simas, Alyson E Fournier","doi":"10.1002/wsbm.1594","DOIUrl":"https://doi.org/10.1002/wsbm.1594","url":null,"abstract":"Central nervous system (CNS) inflammation is a key factor in multiple sclerosis (MS). Invasion of peripheral immune cells into the CNS resulting from an unknown signal or combination of signals results in activation of resident immune cells and the hallmark feature of the disease: demyelinating lesions. These lesion sites are an amalgam of reactive peripheral and central immune cells, astrocytes, damaged and dying oligodendrocytes, and injured neurons and axons. Sustained inflammation affects cells directly located within the lesion site and further abnormalities are apparent diffusely throughout normal-appearing white matter and grey matter. It is only relatively recently, using animal models, new tissue sampling techniques, and next-generation sequencing, that molecular changes occurring in CNS resident cells have been broadly captured. Advances in cell isolation through Fluorescence Activated Cell Sorting (FACS) and laser-capture microdissection together with the emergence of single-cell sequencing have enabled researchers to investigate changes in gene expression in astrocytes, microglia, and oligodendrocytes derived from animal models of MS as well as from primary patient tissue. The contribution of some dysregulated pathways has been followed up in individual studies; however, corroborating results often go unreported between sequencing studies. To this end, we have consolidated results from numerous RNA-sequencing studies to identify and review novel patterns of differentially regulated genes and pathways occurring within CNS glial cells in MS. This article is categorized under: Neurological Diseases > Molecular and Cellular Physiology.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"15 2","pages":"e1594"},"PeriodicalIF":3.1,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9680032","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: 2

In silico modeling for the hepatic circulation and transport: From the liver organ to lobules. 肝脏循环和运输的计算机模拟:从肝器官到小叶。

IF 3.1 3区医学

WIREs Mechanisms of Disease Pub Date : 2023-03-01 DOI: 10.1002/wsbm.1586

Harvey Ho, Shawn Means, Soroush Safaei, Peter John Hunter

{"title":"In silico modeling for the hepatic circulation and transport: From the liver organ to lobules.","authors":"Harvey Ho, Shawn Means, Soroush Safaei, Peter John Hunter","doi":"10.1002/wsbm.1586","DOIUrl":"https://doi.org/10.1002/wsbm.1586","url":null,"abstract":"The function of the liver depends critically on its blood supply. Numerous in silico models have been developed to study various aspects of the hepatic circulation, including not only the macro-hemodynamics at the organ level, but also the microcirculation at the lobular level. In addition, computational models of blood flow and bile flow have been used to study the transport, metabolism, and clearance of drugs in pharmacokinetic studies. These in silico models aim to provide insights into the liver organ function under both healthy and diseased states, and to assist quantitative analysis for surgical planning and postsurgery treatment. The purpose of this review is to provide an update on state-of-the-art in silico models of the hepatic circulation and transport processes. We introduce the numerical methods and the physiological background of these models. We also discuss multiscale frameworks that have been proposed for the liver, and their linkage with the large context of systems biology, systems pharmacology, and the Physiome project. This article is categorized under: Metabolic Diseases > Computational Models Metabolic Diseases > Biomedical Engineering Cardiovascular Diseases > Computational Models.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"15 2","pages":"e1586"},"PeriodicalIF":3.1,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9329645","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

Organoids of the male reproductive system: Challenges, opportunities, and their potential use in fertility research. 男性生殖系统类器官:挑战、机遇及其在生育研究中的潜在应用。

IF 3.1 3区医学

WIREs Mechanisms of Disease Pub Date : 2023-03-01 DOI: 10.1002/wsbm.1590

Daniela Patrício, Joana Santiago, João F Mano, Margarida Fardilha

{"title":"Organoids of the male reproductive system: Challenges, opportunities, and their potential use in fertility research.","authors":"Daniela Patrício, Joana Santiago, João F Mano, Margarida Fardilha","doi":"10.1002/wsbm.1590","DOIUrl":"https://doi.org/10.1002/wsbm.1590","url":null,"abstract":"Organoids are units of function of a given organ able to reproduce, in culture, a biological structure similar in architecture and function to its counterpart in vivo. Today, it is possible to develop an organoid from a fragment of tissue, a stem cell located in an adult organ, an embryonic stem cell, or an induced pluripotent stem cell. In the past decade, many organoids have been developed which mimic stomach, pancreas, liver and brain tissues, optic cups, among many others. Additionally, different male reproductive system organs have already been developed as organoids, including the prostate and testis. These 3D cultures may be of great importance for urological cancer research and have the potential to be used in fertility research for the study of spermatozoa production and maturation, germ cells-somatic cells interactions, and mechanisms of disease. They also provide an accurate preclinical pipeline for drug testing and discovery, as well as for the study of drug resistance. In this work, we revise the current knowledge on organoid technology and its use in healthcare and research, describe the male reproductive system organoids and other biomaterials already developed, and discuss their current application. Finally, we highlight the research gaps, challenges, and opportunities in the field and propose strategies to improve the use of organoids for the study of male infertility situations. This article is categorized under: Reproductive System Diseases > Stem Cells and Development Reproductive System Diseases > Biomedical Engineering.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"15 2","pages":"e1590"},"PeriodicalIF":3.1,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9329662","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: 5

Determination of the Salmonella intracellular lifestyle by the diversified interaction of Type III secretion system effectors and host GTPases. III型分泌系统效应物与宿主gtpase多种相互作用对沙门氏菌胞内生活方式的影响。

IF 3.1 3区医学

WIREs Mechanisms of Disease Pub Date : 2023-03-01 DOI: 10.1002/wsbm.1587

Kun Meng, Ping Zhu, Liuliu Shi, Shan Li

引用次数: 0

Neurodegeneration in multiple sclerosis. 多发性硬化症的神经变性。

IF 4.6 3区医学

WIREs Mechanisms of Disease Pub Date : 2023-01-01 Epub Date: 2022-08-10 DOI: 10.1002/wsbm.1583

Gabrielle M Mey, Kedar R Mahajan, Tara M DeSilva

{"title":"Neurodegeneration in multiple sclerosis.","authors":"Gabrielle M Mey, Kedar R Mahajan, Tara M DeSilva","doi":"10.1002/wsbm.1583","DOIUrl":"10.1002/wsbm.1583","url":null,"abstract":"Axonal loss in multiple sclerosis (MS) is a key component of disease progression and permanent neurologic disability. MS is a heterogeneous demyelinating and neurodegenerative disease of the central nervous system (CNS) with varying presentation, disease courses, and prognosis. Immunomodulatory therapies reduce the frequency and severity of inflammatory demyelinating events that are a hallmark of MS, but there is minimal therapy to treat progressive disease and there is no cure. Data from patients with MS, post-mortem histological analysis, and animal models of demyelinating disease have elucidated patterns of MS pathogenesis and underlying mechanisms of neurodegeneration. MRI and molecular biomarkers have been proposed to identify predictors of neurodegeneration and risk factors for disease progression. Early signs of axonal dysfunction have come to light including impaired mitochondrial trafficking, structural axonal changes, and synaptic alterations. With sustained inflammation as well as impaired remyelination, axons succumb to degeneration contributing to CNS atrophy and worsening of disease. These studies highlight the role of chronic demyelination in the CNS in perpetuating axonal loss, and the difficulty in promoting remyelination and repair amidst persistent inflammatory insult. Regenerative and neuroprotective strategies are essential to overcome this barrier, with early intervention being critical to rescue axonal integrity and function. The clinical and basic research studies discussed in this review have set the stage for identifying key propagators of neurodegeneration in MS, leading the way for neuroprotective therapeutic development. This article is categorized under: Immune System Diseases > Molecular and Cellular Physiology Neurological Diseases > Molecular and Cellular Physiology.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"15 1","pages":"e1583"},"PeriodicalIF":4.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9279036","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

Evolution of precision oncology-guided treatment paradigms. 精准肿瘤指导治疗模式的演变。

IF 3.1 3区医学

WIREs Mechanisms of Disease Pub Date : 2023-01-01 DOI: 10.1002/wsbm.1585

Ramanuj DasGupta, Aixin Yap, Elena Yong Yaqing, Shumei Chia

{"title":"Evolution of precision oncology-guided treatment paradigms.","authors":"Ramanuj DasGupta, Aixin Yap, Elena Yong Yaqing, Shumei Chia","doi":"10.1002/wsbm.1585","DOIUrl":"https://doi.org/10.1002/wsbm.1585","url":null,"abstract":"Cancer treatment is gradually evolving from the classical use of nonspecific cytotoxic drugs targeting generic mechanisms of cell growth and proliferation. Instead, new \"patient-specific treatment paradigms\" that are based on an individual patient's tumor-specific molecular features are emerging, and these include \"druggable\" genomic alterations such as oncogenic driver mutations, downstream activities of cancer-signaling pathways, and the expression of specific genes involved in tumorigenesis and cancer progression. This evolving landscape of making evidence-based treatment decisions forms the foundation of precision oncology, which aims to deliver \"the right drug, to the right patient and at the right time\". The long-term vision for this approach is to maximize the treatment efficacy while minimizing exposure to ineffective therapy and reducing co-morbidity-related side effects. Successful clinical translation and implementation of this vision have the potential to revolutionize treatment paradigms from predominantly reactive, to more evidence-based, proactive and predictive care. In this article, we review the past and current approaches in precision oncology, and describe their remarkable power and limitations. We also speculate on the evolution of newly emerging methodologies of the future that can be used to address some of the key challenges associated with the existing paradigms. This article is categorized under: Cancer > Genetics/Genomics/Epigenetics Cancer > Molecular and Cellular Physiology Cancer > Computational Models.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"15 1","pages":"e1585"},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10623545","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

Computational models for generating microvascular structures: Investigations beyond medical imaging resolution. 生成微血管结构的计算模型:超越医学成像分辨率的研究。

IF 3.1 3区医学

WIREs Mechanisms of Disease Pub Date : 2023-01-01 DOI: 10.1002/wsbm.1579

Cameron Apeldoorn, Soroush Safaei, Julian Paton, Gonzalo D Maso Talou

{"title":"Computational models for generating microvascular structures: Investigations beyond medical imaging resolution.","authors":"Cameron Apeldoorn, Soroush Safaei, Julian Paton, Gonzalo D Maso Talou","doi":"10.1002/wsbm.1579","DOIUrl":"https://doi.org/10.1002/wsbm.1579","url":null,"abstract":"Angiogenesis, arteriogenesis, and pruning are revascularization processes essential to our natural vascular development and adaptation, as well as central players in the onset and development of pathologies such as tumoral growth and stroke recovery. Computational modeling allows for repeatable experimentation and exploration of these complex biological processes. In this review, we provide an introduction to the biological understanding of the vascular adaptation processes of sprouting angiogenesis, intussusceptive angiogenesis, anastomosis, pruning, and arteriogenesis, discussing some of the more significant contributions made to the computational modeling of these processes. Each computational model represents a theoretical framework for how biology functions, and with rises in computing power and study of the problem these frameworks become more accurate and complete. We highlight physiological, pathological, and technological applications that can be benefit from the advances performed by these models, and we also identify which elements of the biology are underexplored in the current state-of-the-art computational models. This article is categorized under: Cancer > Computational Models Cardiovascular Diseases > Computational Models.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"15 1","pages":"e1579"},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10077909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9265637","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: 3

Models of the cardiac L-type calcium current: A quantitative review. 心脏 L 型钙电流模型：定量综述。

IF 4.6 3区医学

WIREs Mechanisms of Disease Pub Date : 2023-01-01 Epub Date: 2022-08-26 DOI: 10.1002/wsbm.1581

Aditi Agrawal, Ken Wang, Liudmila Polonchuk, Jonathan Cooper, Maurice Hendrix, David J Gavaghan, Gary R Mirams, Michael Clerx

{"title":"Models of the cardiac L-type calcium current: A quantitative review.","authors":"Aditi Agrawal, Ken Wang, Liudmila Polonchuk, Jonathan Cooper, Maurice Hendrix, David J Gavaghan, Gary R Mirams, Michael Clerx","doi":"10.1002/wsbm.1581","DOIUrl":"10.1002/wsbm.1581","url":null,"abstract":"The L-type calcium current ( <math> <mrow><msub><mi>I</mi> <mi>CaL</mi></msub> </mrow> </math> ) plays a critical role in cardiac electrophysiology, and models of <math> <mrow><msub><mi>I</mi> <mi>CaL</mi></msub> </mrow> </math> are vital tools to predict arrhythmogenicity of drugs and mutations. Five decades of measuring and modeling <math> <mrow><msub><mi>I</mi> <mi>CaL</mi></msub> </mrow> </math> have resulted in several competing theories (encoded in mathematical equations). However, the introduction of new models has not typically been accompanied by a data-driven critical comparison with previous work, so that it is unclear which model is best suited for any particular application. In this review, we describe and compare 73 published mammalian <math> <mrow><msub><mi>I</mi> <mi>CaL</mi></msub> </mrow> </math> models and use simulated experiments to show that there is a large variability in their predictions, which is not substantially diminished when grouping by species or other categories. We provide model code for 60 models, list major data sources, and discuss experimental and modeling work that will be required to reduce this huge list of competing theories and ultimately develop a community consensus model of <math> <mrow><msub><mi>I</mi> <mi>CaL</mi></msub> </mrow> </math> . This article is categorized under: Cardiovascular Diseases > Computational Models Cardiovascular Diseases > Molecular and Cellular Physiology.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"15 1","pages":"e1581"},"PeriodicalIF":4.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10078428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9279049","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

The cardiac wound healing response to myocardial infarction. 心肌梗死后心脏伤口愈合的反应。

IF 3.1 3区医学

WIREs Mechanisms of Disease Pub Date : 2023-01-01 DOI: 10.1002/wsbm.1584

Upendra Chalise, Mediha Becirovic-Agic, Merry L Lindsey

{"title":"The cardiac wound healing response to myocardial infarction.","authors":"Upendra Chalise, Mediha Becirovic-Agic, Merry L Lindsey","doi":"10.1002/wsbm.1584","DOIUrl":"https://doi.org/10.1002/wsbm.1584","url":null,"abstract":"Myocardial infarction (MI) is defined as evidence of myocardial necrosis consistent with prolonged ischemia. In response to MI, the myocardium undergoes a series of wound healing events that initiate inflammation and shift to anti-inflammation before transitioning to tissue repair that culminates in scar formation to replace the region of the necrotic myocardium. The overall response to MI is determined by two major steps, the first of which is the secretion of proteases by infiltrating leukocytes to breakdown extracellular matrix (ECM) components, a necessary step to remove necrotic cardiomyocytes. The second step is the generation of new ECM that comprises the scar; and this step is governed by the cardiac fibroblasts as the major source of new ECM synthesis. The leukocyte component resides in the middle of the two-step process, contributing to both sides as the leukocytes transition from pro-inflammatory to anti-inflammatory and reparative cell phenotypes. The balance between the two steps determines the final quantity and quality of scar formed, which in turn contributes to chronic outcomes following MI, including the progression to heart failure. This review will summarize our current knowledge regarding the cardiac wound healing response to MI, primarily focused on experimental models of MI in mice. This article is categorized under: Cardiovascular Diseases > Molecular and Cellular Physiology Immune System Diseases > Molecular and Cellular Physiology.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"15 1","pages":"e1584"},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d2/3a/WSBM-15-0.PMC10077990.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10642805","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: 6

Fluids and flows in brain cancer and neurological disorders. 脑癌和神经系统疾病的体液流动。

IF 3.1 3区医学

WIREs Mechanisms of Disease Pub Date : 2023-01-01 DOI: 10.1002/wsbm.1582

Peng Jin, Jennifer M Munson

{"title":"Fluids and flows in brain cancer and neurological disorders.","authors":"Peng Jin, Jennifer M Munson","doi":"10.1002/wsbm.1582","DOIUrl":"https://doi.org/10.1002/wsbm.1582","url":null,"abstract":"Interstitial fluid (IF) and cerebrospinal fluid (CSF) are an integral part of the brain, serving to cushion and protect the brain parenchymal cells against damage and aid in their function. The brain IF contains various ions, nutrients, waste products, peptides, hormones, and neurotransmitters. IF moves primarily by pressure-dependent bulk flow through brain parenchyma, draining into the ventricular CSF. The brain ventricles and subarachnoid spaces are filled with CSF which circulates through the perivascular spaces. It also flows into the IF space regulated, in part, by aquaporin channels, removing waste solutes through a process of IF-CSF mixing. During disease development, the composition, flow, and volume of these fluids changes and can lead to brain cell dysfunction. With the improvement of imaging technology and the help of genomic profiling, more information has been and can be obtained from brain fluids; however, the role of CSF and IF in brain cancer and neurobiological disease is still limited. Here we outline recent advances of our knowledge of brain fluid flow in cancer and neurodegenerative disease based on our understanding of its dynamics and composition. This article is categorized under: Cancer > Biomedical Engineering Neurological Diseases > Biomedical Engineering.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"15 1","pages":"e1582"},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/dc/89/WSBM-15-0.PMC9869390.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9271944","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: 2