WIREs Mechanisms of Disease最新文献

{"title":"Regenerative mesenchymal stem cell-derived extracellular vesicles: A potential alternative to cell-based therapy in viral infection and disease damage control.","authors":"Ayodeji O Ipinmoroti,&nbsp;Rachana Pandit,&nbsp;Qiana L Matthews","doi":"10.1002/wsbm.1574","DOIUrl":"https://doi.org/10.1002/wsbm.1574","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) released by regenerative cells such as mesenchymal stem cells are effective facilitators of healing, therapy, and repair. Conversely, EVs released from infected and/or diseased cells could be useful as markers in the detection and diagnosis of disease conditions such as cancer at their earliest most detectable, and treatable stage. A very important type of EVs, termed exosomes offer a hypothetical new paradigm in disease detection, diagnosis, and treatment. A broad range of exosome-based biomedical and therapeutic applications are now being evaluated in recent clinical trials. Exosomes are found in virtually all bodily fluids and cells and are capable of crossing tight junctions and toughly regulated boundaries such as the blood-brain barrier. Exosomes' expedition ends when they are taken up by bystander cells which corroborates the fact that they are conduits for cells releasing them. Exosomes released by diseased cells have been associated with cell-to-cell progression of diseases like viral disease, neurodegeneration, and certain cancers. Due to high discrimination in most disease conditions, exosome uptake is usually cell-specific. Lots of research evidence have revealed that infusion of exosomes derived from regenerative cells such as stem cells could impede the development of certain infections and age-related diseases by activating self-repair machinery through RNA, DNA, protein, and lipid transfer between cells in patients. They have also been demonstrated in the restoration of the circulating population of exosomes in tissues and the fluid of recipients. The first human clinical trials of exosome therapies are now underway, establishing the future of regenerative exosome in regenerative medicine. This article is categorized under: Cancer > Stem Cells and Development Immune System Diseases > Stem Cells and Development Immune System Diseases > Molecular and Cellular Physiology.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":" ","pages":"e1574"},"PeriodicalIF":3.1,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40352664","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}

{"title":"Recent advances in the molecular basis of chemotherapy resistance and potential application of epigenetic therapeutics in chemorefractory renal cell carcinoma.","authors":"Narayan Acharya,&nbsp;Kamaleshwar P Singh","doi":"10.1002/wsbm.1575","DOIUrl":"https://doi.org/10.1002/wsbm.1575","url":null,"abstract":"<p><p>Among various types of cancers, kidney cancer is unique with respect to a low frequency of mutations and a relatively higher level of chemotherapy resistance. Resistance to chemotherapy is a major challenge in kidney cancer treatment in the clinic. Tremendous progress has been made in identifying the molecular changes associated with chemotherapy resistance in RCC. However, the exact contribution of these molecular changes to the acquisition of chemotherapy resistance is not fully understood. In addition to genetic changes, epigenetic alterations have been shown to contribute to various pathways associated with chemotherapy resistance, such as increased cell proliferation and survival, regulation of drug influx and efflux transporters, increased DNA repair, loss of DNA-damage-dependent apoptotic potential, cellular dedifferentiation to cancer stem cell, and epithelial-mesenchymal transitions (EMT). Moreover, recent studies suggest that epigenetic aberrations that can be reversed by epigenetic therapeutics can potentially be targeted to restore chemosensitivity in chemorefractory kidney cancer. This review article highlights current knowledge of the role of genetic and epigenetic aberrations as well as the physiological and metabolic changes associated with chemotherapeutic resistance. Additionally, current approaches and future directions for overcoming chemotherapeutic resistance including the potential of epigenetic therapeutic in chemorefractory kidney cancer have also been discussed. This article is categorized under: Cancer > Genetics/Genomics/Epigenetics.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":" ","pages":"e1575"},"PeriodicalIF":3.1,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40541596","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}

{"title":"Molecular mechanisms underlying bacterial resistance to ceftazidime/avibactam.","authors":"Luying Xiong,&nbsp;Xueting Wang,&nbsp;Yuan Wang,&nbsp;Wei Yu,&nbsp;Yanzi Zhou,&nbsp;Xiaohui Chi,&nbsp;Tingting Xiao,&nbsp;Yonghong Xiao","doi":"10.1002/wsbm.1571","DOIUrl":"https://doi.org/10.1002/wsbm.1571","url":null,"abstract":"<p><p>Ceftazidime/avibactam (CAZ/AVI), a combination of ceftazidime and a novel β-lactamase inhibitor (avibactam) that has been approved by the U.S. Food and Drug Administration, the European Union, and the National Regulatory Administration in China. CAZ/AVI is used mainly to treat complicated urinary tract infections and complicated intra-abdominal infections in adults, as well as to treat patients infected with Carbapenem-resistant Enterobacteriaceae (CRE) susceptible to CAZ/AVI. However, increased clinical application of CAZ/AVI has resulted in the development of resistant strains. Mechanisms of resistance in most of these strains have been attributed to bla_KPC mutations, which lead to amino acid substitutions in β-lactamase and changes in gene expression. Resistance to CAZ/AVI is also associated with reduced expression and loss of outer membrane proteins or overexpression of efflux pumps. In this review, the prevalence of CAZ/AVI-resistance bacteria, resistance mechanisms, and selection of detection methods of CAZ/AVI are demonstrated, aiming to provide scientific evidence for the clinical prevention and treatment of CAZ/AVI resistant strains, and provide guidance for the development of new drugs. This article is categorized under: Infectious Diseases > Molecular and Cellular Physiology.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"14 6","pages":"e1571"},"PeriodicalIF":3.1,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9788277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10445244","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}

{"title":"A compendium of validated pain genes.","authors":"Eric Wistrom, Rebecca Chase, Patrick R Smith, Zachary T Campbell","doi":"10.1002/wsbm.1570","DOIUrl":"10.1002/wsbm.1570","url":null,"abstract":"<p><p>The development of novel pain therapeutics hinges on the identification and rigorous validation of potential targets. Model organisms provide a means to test the involvement of specific genes and regulatory elements in pain. Here we provide a list of genes linked to pain-associated behaviors. We capitalize on results spanning over three decades to identify a set of 242 genes. They support a remarkable diversity of functions spanning action potential propagation, immune response, GPCR signaling, enzymatic catalysis, nucleic acid regulation, and intercellular signaling. Making use of existing tissue and single-cell high-throughput RNA sequencing datasets, we examine their patterns of expression. For each gene class, we discuss archetypal members, with an emphasis on opportunities for additional experimentation. Finally, we discuss how powerful and increasingly ubiquitous forward genetic screening approaches could be used to improve our ability to identify pain genes. This article is categorized under: Neurological Diseases > Genetics/Genomics/Epigenetics Neurological Diseases > Molecular and Cellular Physiology.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"14 6","pages":"e1570"},"PeriodicalIF":4.6,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9787016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10436299","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}

{"title":"Pathogenesis of neural tube defects: The regulation and disruption of cellular processes underlying neural tube closure.","authors":"David M Engelhardt,&nbsp;Cara A Martyr,&nbsp;Lee Niswander","doi":"10.1002/wsbm.1559","DOIUrl":"https://doi.org/10.1002/wsbm.1559","url":null,"abstract":"<p><p>Neural tube closure (NTC) is crucial for proper development of the brain and spinal cord and requires precise morphogenesis from a sheet of cells to an intact three-dimensional structure. NTC is dependent on successful regulation of hundreds of genes, a myriad of signaling pathways, concentration gradients, and is influenced by epigenetic and environmental cues. Failure of NTC is termed a neural tube defect (NTD) and is a leading class of congenital defects in the United States and worldwide. Though NTDs are all defined as incomplete closure of the neural tube, the pathogenesis of an NTD determines the type, severity, positioning, and accompanying phenotypes. In this review, we survey pathogenesis of NTDs relating to disruption of cellular processes arising from genetic mutations, altered epigenetic regulation, and environmental influences by micronutrients and maternal condition. This article is categorized under: Congenital Diseases > Genetics/Genomics/Epigenetics Neurological Diseases > Genetics/Genomics/Epigenetics Neurological Diseases > Stem Cells and Development.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"14 5","pages":"e1559"},"PeriodicalIF":3.1,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9605354/pdf/nihms-1799087.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10134712","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}

{"title":"Development and diseases of the coronary microvasculature and its communication with the myocardium.","authors":"Kristýna Neffeová,&nbsp;Veronika Olejníčková,&nbsp;Ondřej Naňka,&nbsp;Hana Kolesová","doi":"10.1002/wsbm.1560","DOIUrl":"https://doi.org/10.1002/wsbm.1560","url":null,"abstract":"<p><p>We review the current understanding of formation and development of the coronary microvasculature which supplies oxygen and nutrients to the heart myocardium and removes waste. We emphasize the close relationship, mutual development, and communication between microvasculature endothelial cells and surrounding cardiomyocytes. The first part of the review is focused on formation of microvasculature during embryonic development. We summarize knowledge about establishing the heart microvasculature density based on diffusion distance. Then signaling mechanisms which are involved in forming the microvasculature are discussed. This includes details of cardiomyocyte-endothelial cell interactions involving hypoxia, VEGF, NOTCH, angiopoietin, PDGF, and other signaling factors. The microvasculature is understudied due to difficulties in its visualization. Therefore, currently available imaging methods to delineate the coronary microvasculature in development and in adults are discussed. The second part of the review is dedicated to the importance of the coronary vasculature in disease. Coronary microvasculature pathologies are present in many congenital heart diseases (CHD), especially in pulmonary atresia, and worsen outcomes. In CHDs, where the development of the myocardium is impaired, microvasculature is also affected. In adult patients coronary microvascular disease is one of the main causes of sudden cardiac death, especially in women. Coronary microvasculature pathologies affect myocardial ischemia and vice versa; myocardial pathologies such as cardiomyopathies are closely connected with coronary microvasculature dysfunction. Microvasculature inflammation also worsens the outcomes of COVID-19 disease. Our review stresses the importance of coronary microvasculature and provides an overview of its formation and signaling mechanisms and the importance of coronary vasculature pathologies in CHDs and adult diseases. This article is categorized under: Cardiovascular Diseases > Stem Cells and Development Congenital Diseases > Molecular and Cellular Physiology Cardiovascular Diseases > Molecular and Cellular Physiology.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":" ","pages":"e1560"},"PeriodicalIF":3.1,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40164570","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}

{"title":"Systems biology of angiogenesis signaling: Computational models and omics.","authors":"Yu Zhang,&nbsp;Hanwen Wang,&nbsp;Rebeca Hannah M Oliveira,&nbsp;Chen Zhao,&nbsp;Aleksander S Popel","doi":"10.1002/wsbm.1550","DOIUrl":"https://doi.org/10.1002/wsbm.1550","url":null,"abstract":"<p><p>Angiogenesis is a highly regulated multiscale process that involves a plethora of cells, their cellular signal transduction, activation, proliferation, differentiation, as well as their intercellular communication. The coordinated execution and integration of such complex signaling programs is critical for physiological angiogenesis to take place in normal growth, development, exercise, and wound healing, while its dysregulation is critically linked to many major human diseases such as cancer, cardiovascular diseases, and ocular disorders; it is also crucial in regenerative medicine. Although huge efforts have been devoted to drug development for these diseases by investigation of angiogenesis-targeted therapies, only a few therapeutics and targets have proved effective in humans due to the innate multiscale complexity and nonlinearity in the process of angiogenic signaling. As a promising approach that can help better address this challenge, systems biology modeling allows the integration of knowledge across studies and scales and provides a powerful means to mechanistically elucidate and connect the individual molecular and cellular signaling components that function in concert to regulate angiogenesis. In this review, we summarize and discuss how systems biology modeling studies, at the pathway-, cell-, tissue-, and whole body-levels, have advanced our understanding of signaling in angiogenesis and thereby delivered new translational insights for human diseases. This article is categorized under: Cardiovascular Diseases > Computational Models Cancer > Computational Models.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":" ","pages":"e1550"},"PeriodicalIF":3.1,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39636617","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}

{"title":"New developments in the biology of fibroblast growth factors.","authors":"David M Ornitz,&nbsp;Nobuyuki Itoh","doi":"10.1002/wsbm.1549","DOIUrl":"https://doi.org/10.1002/wsbm.1549","url":null,"abstract":"<p><p>The fibroblast growth factor (FGF) family is composed of 18 secreted signaling proteins consisting of canonical FGFs and endocrine FGFs that activate four receptor tyrosine kinases (FGFRs 1-4) and four intracellular proteins (intracellular FGFs or iFGFs) that primarily function to regulate the activity of voltage-gated sodium channels and other molecules. The canonical FGFs, endocrine FGFs, and iFGFs have been reviewed extensively by us and others. In this review, we briefly summarize past reviews and then focus on new developments in the FGF field since our last review in 2015. Some of the highlights in the past 6 years include the use of optogenetic tools, viral vectors, and inducible transgenes to experimentally modulate FGF signaling, the clinical use of small molecule FGFR inhibitors, an expanded understanding of endocrine FGF signaling, functions for FGF signaling in stem cell pluripotency and differentiation, roles for FGF signaling in tissue homeostasis and regeneration, a continuing elaboration of mechanisms of FGF signaling in development, and an expanding appreciation of roles for FGF signaling in neuropsychiatric diseases. This article is categorized under: Cardiovascular Diseases > Molecular and Cellular Physiology Neurological Diseases > Molecular and Cellular Physiology Congenital Diseases > Stem Cells and Development Cancer > Stem Cells and Development.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"14 4","pages":"e1549"},"PeriodicalIF":3.1,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10115509/pdf/nihms-1890656.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9732920","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}

{"title":"Patterning of the antero-ventral mammalian brain: Lessons from holoprosencephaly comparative biology in man and mouse.","authors":"Kristen S Barratt,&nbsp;Kyle A Drover,&nbsp;Zoe M Thomas,&nbsp;Ruth M Arkell","doi":"10.1002/wsbm.1552","DOIUrl":"https://doi.org/10.1002/wsbm.1552","url":null,"abstract":"<p><p>Adult form and function are dependent upon the activity of specialized signaling centers that act early in development at the embryonic midline. These centers instruct the surrounding cells to adopt a positional fate and to form the patterned structures of the phylotypic embryo. Abnormalities in these processes have devastating consequences for the individual, as exemplified by holoprosencephaly in which anterior midline development fails, leading to structural defects of the brain and/or face. In the 25 years since the first association between human holoprosencephaly and the sonic hedgehog gene, a combination of human and animal genetic studies have enhanced our understanding of the genetic and embryonic causation of this congenital defect. Comparative biology has extended the holoprosencephaly network via the inclusion of gene mutations from multiple signaling pathways known to be required for anterior midline formation. It has also clarified aspects of holoprosencephaly causation, showing that it arises when a deleterious variant is present within a permissive genome, and that environmental factors, as well as embryonic stochasticity, influence the phenotypic outcome of the variant. More than two decades of research can now be distilled into a framework of embryonic and genetic causation. This framework means we are poised to move beyond our current understanding of variants in signaling pathway molecules. The challenges now at the forefront of holoprosencephaly research include deciphering how the mutation of genes involved in basic cell processes can also cause holoprosencephaly, determining the important constituents of the holoprosencephaly permissive genome, and identifying environmental compounds that promote holoprosencephaly. This article is categorized under: Congenital Diseases > Stem Cells and Development Congenital Diseases > Genetics/Genomics/Epigenetics Congenital Diseases > Molecular and Cellular Physiology Congenital Diseases > Environmental Factors.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":" ","pages":"e1552"},"PeriodicalIF":3.1,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39778499","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}

{"title":"The role of gut microbiota in infectious diseases.","authors":"Yongjie Cai,&nbsp;Lingming Chen,&nbsp;Sien Zhang,&nbsp;Lingchan Zeng,&nbsp;Gucheng Zeng","doi":"10.1002/wsbm.1551","DOIUrl":"https://doi.org/10.1002/wsbm.1551","url":null,"abstract":"<p><p>The intestine, the largest immune organ in the human body, harbors approximately 10¹³ microorganisms, including bacteria, fungi, viruses, and other unknown microbes. The intestine is a most important crosstalk anatomic structure between the first (the host) and second (the microorganisms) genomes. The imbalance of the intestinal microecology, especially dysbiosis of the composition, structure, and function of gut microbiota, is linked to human diseases. In this review, we investigated the roles and underlying mechanisms of gut microecology in the development, progression, and prognosis of infectious diseases. Furthermore, we discussed potential new strategies of prevention and treatment for infectious diseases based on manipulating the composition, structure, and function of intestinal microorganisms in the future. This article is categorized under: Infectious Diseases > Molecular and Cellular Physiology.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":" ","pages":"e1551"},"PeriodicalIF":3.1,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39777667","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}