Molecular Aspects of Medicine最新文献_第9页

Systems to model the personalized aspects of microbiome health and gut dysbiosis 对微生物组健康和肠道微生态失调的个性化方面进行建模的系统

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-06-01 DOI: 10.1016/j.mam.2022.101115

Cristina Matthewman , Alexandra Narin , Hannah Huston , Christopher Edward Hopkins

{"title":"Systems to model the personalized aspects of microbiome health and gut dysbiosis","authors":"Cristina Matthewman , Alexandra Narin , Hannah Huston , Christopher Edward Hopkins","doi":"10.1016/j.mam.2022.101115","DOIUrl":"10.1016/j.mam.2022.101115","url":null,"abstract":"<div><p>The human gut microbiome is a complex and dynamic microbial entity that interacts with the environment and other parts of the body including the brain, heart, liver, and immune system. These multisystem interactions are highly conserved from invertebrates to humans, however the complexity and diversity of human microbiota compositions often yield a context that is unique to each individual. Yet commonalities remain across species, where a healthy gut microbiome will be rich in symbiotic commensal biota while an unhealthy gut microbiota will be experiencing abnormal blooms of pathobiont bacteria. In this review we discuss how omics technologies can be applied in a personalized approach to understand the microbial crosstalk and microbial-host interactions that affect the delicate balance between eubiosis and dysbiosis in an individual gut microbiome. We further highlight the strengths of model organisms in identifying and characterizing these conserved synergistic and/or pathogenic host-microbe interactions. And finally, we touch upon the growing area of personalized therapeutic interventions targeting gut microbiome.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9296026","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}

引用次数: 7

The evolving regulatory landscape in regenerative medicine 再生医学监管格局的演变

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-06-01 DOI: 10.1016/j.mam.2022.101138

Danielle J. Beetler , Damian N. Di Florio , Ethan W. Law , Chris M. Groen , Anthony J. Windebank , Quinn P. Peterson , DeLisa Fairweather

{"title":"The evolving regulatory landscape in regenerative medicine","authors":"Danielle J. Beetler , Damian N. Di Florio , Ethan W. Law , Chris M. Groen , Anthony J. Windebank , Quinn P. Peterson , DeLisa Fairweather","doi":"10.1016/j.mam.2022.101138","DOIUrl":"10.1016/j.mam.2022.101138","url":null,"abstract":"<div><p>Regenerative medicine as a field has emerged as a new component of modern medicine and medical research that encompasses a wide range of products including cellular and acellular therapies. As this new field emerged, regulatory agencies like the Food and Drug Administration (FDA) rapidly adapted existing regulatory frameworks to address the transplantation, gene therapy, cell-based therapeutics, and acellular biologics that fall under the broader regenerative medicine umbrella. Where it has not been possible to modify existing regulation and processes, entirely new frameworks have been generated with the intention of providing flexible, forward-facing systems to regulate this rapidly growing field. This review discusses the current state of FDA regulatory affairs in the context of stem cells and extracellular vesicles by highlighting gaps in the current regulatory system and then discussing where regulatory science in regenerative medicine may be headed based on these gaps and the FDA's historical ability to deal with emerging fields. Lastly, we utilize case studies in stem cell and acellular based treatments to demonstrate how regulatory science has evolved in regenerative medicine and highlight the ongoing clinical efforts and challenges of these therapies.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10162454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9416652","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}

引用次数: 5

Phenotypic screening models for rapid diagnosis of genetic variants and discovery of personalized therapeutics 快速诊断遗传变异和发现个性化治疗方法的表型筛选模型

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-06-01 DOI: 10.1016/j.mam.2022.101153

Christopher E. Hopkins , Trisha Brock , Thomas R. Caulfield , Matthew Bainbridge

{"title":"Phenotypic screening models for rapid diagnosis of genetic variants and discovery of personalized therapeutics","authors":"Christopher E. Hopkins , Trisha Brock , Thomas R. Caulfield , Matthew Bainbridge","doi":"10.1016/j.mam.2022.101153","DOIUrl":"10.1016/j.mam.2022.101153","url":null,"abstract":"<div><p>Precision medicine strives for highly individualized treatments for disease under the notion that each individual's unique genetic makeup and environmental exposures imprints upon them not only a disposition to illness, but also an optimal therapeutic approach. In the realm of rare disorders, genetic predisposition is often the predominant mechanism driving disease presentation. For such, mostly, monogenic disorders, a causal gene to phenotype association is likely. As a result, it becomes important to query the patient's genome for the presence of pathogenic variations that are likely to cause the disease. Determining whether a variant is pathogenic or not is critical to these analyses and can be challenging, as many disease-causing variants are novel and, <em>ergo</em>, have no available functional data to help categorize them. This problem is exacerbated by the need for rapid evaluation of pathogenicity, since many genetic diseases present in young children who will experience increased morbidity and mortality without rapid diagnosis and therapeutics. Here, we discuss the utility of animal models, with a focus mainly on <em>C. elegans</em>, as a contrast to tissue culture and <em>in silico</em> approaches, with emphasis on how these systems are used in determining pathogenicity of variants with uncertain significance and then used to screen for novel therapeutics.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10073243/pdf/nihms-1855177.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9913306","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}

引用次数: 5

Extracellular vesicles in the glioblastoma microenvironment: A diagnostic and therapeutic perspective 胶质母细胞瘤微环境中的细胞外小泡：诊断和治疗前景

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-06-01 DOI: 10.1016/j.mam.2022.101167

Marissa N. Russo , Lauren A. Whaley , Emily S. Norton , Natanael Zarco , Hugo Guerrero-Cázares

引用次数: 1

Non-canonical roles of Siglecs: Beyond sialic acid-binding and immune cell modulation Siglecs的非规范作用：超越唾液酸结合和免疫细胞调节

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-04-01 DOI: 10.1016/j.mam.2022.101145

Shoib Sarwar Siddiqui

{"title":"Non-canonical roles of Siglecs: Beyond sialic acid-binding and immune cell modulation","authors":"Shoib Sarwar Siddiqui","doi":"10.1016/j.mam.2022.101145","DOIUrl":"10.1016/j.mam.2022.101145","url":null,"abstract":"<div><p>Siglecs (Sialic acid-binding immunoglobulin-type lectins) are I-type lectins that bind with sialic acid ligands (Sia). Most are expressed on the surface of leukocytes and are involved in immune regulation and possess immune tyrosine-based inhibitory motif (ITIM) in the intracellular domain, thus leading to inhibition of the immune response. This signaling is instrumental in maintaining quiescence under physiological conditions and acts as a brake for inflammatory cascades. By contrast, activating Siglecs carry positively charged residues in the transmembrane domain and interact with immune tyrosine-based activating motif (ITAM)-containing proteins, a DNAX-activating protein of 10–12 kDa (DAP10/12), to activate immune cells. There are various characteristics of Siglecs that do not fit within the classification of Siglec receptors as being either inhibitory or activating in nature. This review focuses on elucidating the non-canonical functions and interactions of Siglec receptors, which include Sia-independent interactions such as protein-protein interactions and interactions with lipids or other sugars. This review also summarizes Siglec expression and function on non-immune cells, and non-classical signaling of the receptor. Thus, this review will be beneficial to researchers interested in the field of Siglecs and sialic acid biology.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9309376","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}

引用次数: 4

CD33 isoforms in microglia and Alzheimer's disease: Friend and foe 小胶质细胞中CD33亚型与阿尔茨海默病：朋友与敌人

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-04-01 DOI: 10.1016/j.mam.2022.101111

Ghazaleh Eskandari-Sedighi , Jaesoo Jung , Matthew S. Macauley

引用次数: 12

Human sialoglycan ligands for immune inhibitory Siglecs 免疫抑制性Siglecs的人唾液酸聚糖配体

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-04-01 DOI: 10.1016/j.mam.2022.101110

Anabel Gonzalez-Gil , T. August Li , Jean Kim , Ronald L. Schnaar

{"title":"Human sialoglycan ligands for immune inhibitory Siglecs","authors":"Anabel Gonzalez-Gil , T. August Li , Jean Kim , Ronald L. Schnaar","doi":"10.1016/j.mam.2022.101110","DOIUrl":"10.1016/j.mam.2022.101110","url":null,"abstract":"<div><p>Most human Siglecs (sialic acid binding immunoglobulin-like lectins) are expressed on the surfaces of overlapping subsets of immune cells, and most carry immunoreceptor tyrosine-based inhibitory domains on their intracellular motifs. When immune inhibitory Siglecs bind to complementary sialoglycans in their local milieu, engagement results in down-regulation of the immune response. Siglecs have come under scrutiny as potential targets of drugs to modify the course of inflammation (and other immune system responses) and as immune checkpoints in cancer. Human Siglecs bind to endogenous human sialoglycans. The identities of these endogenous human sialoglycan immune regulators are beginning to emerge, along with some general principles that may inform future investigations in this area. Among these principles is the finding that a cell type or tissue may express a ligand for a particular Siglec on a single or a very few of its sialoglycoproteins. The selected protein carrier for a particular Siglec may be unique in a certain tissue, but vary tissue-to-tissue. The binding affinity of endogenous Siglec ligands may surpass that of its binding to synthetic sialoglycan determinants by several orders of magnitude. Since most human Siglecs have evolved rapidly and are distinct from those in most other mammals, this review describes endogenous human Siglec ligands for several human immune inhibitory Siglecs. As the identities of these immune regulatory sialoglycan ligands are defined, additional opportunities to target Siglecs therapeutically may emerge.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10746161","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}

引用次数: 6

Siglec receptors as new immune checkpoints in cancer Siglec受体作为癌症新的免疫检查点

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-04-01 DOI: 10.1016/j.mam.2022.101112

Michal A. Stanczak , Heinz Läubli

引用次数: 18

Siglecs in allergy and asthma Siglecs与过敏和哮喘

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-04-01 DOI: 10.1016/j.mam.2022.101104

Bruce S. Bochner , Jeremy A. O'Sullivan , Alan T. Chang , Bradford A. Youngblood

引用次数: 7

Discovery, classification, evolution and diversity of Siglecs Siglecs的发现、分类、进化和多样性

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-04-01 DOI: 10.1016/j.mam.2022.101117

Takashi Angata , Ajit Varki

{"title":"Discovery, classification, evolution and diversity of Siglecs","authors":"Takashi Angata , Ajit Varki","doi":"10.1016/j.mam.2022.101117","DOIUrl":"10.1016/j.mam.2022.101117","url":null,"abstract":"<div><p>Immunoglobulin (Ig) superfamily proteins play diverse roles in vertebrates, including regulation of cellular responses by sensing endogenous or exogenous ligands. Siglecs are a family of glycan-recognizing proteins belonging to the Ig superfamily (i.e., I-type lectins). Siglecs are expressed on various leukocyte types and are involved in diverse aspects of immunity, including the regulation of inflammatory responses, leukocyte proliferation, host–microbe interaction, and cancer immunity. Sialoadhesin/Siglec-1, CD22/Siglec-2, and myelin-associated glycoprotein/Siglec-4 were among the first to be characterized as members of the Siglec family, and along with Siglec-15, they are relatively well-conserved among tetrapods. Conversely, CD33/Siglec-3-related Siglecs (CD33rSiglecs, so named as they show high sequence similarity with CD33/Siglec-3) are encoded in a gene cluster with many interspecies variations and even intraspecies variations within some lineages such as humans. The rapid evolution of CD33rSiglecs expressed on leukocytes involved in innate immunity likely reflects the selective pressure by pathogens that interact and possibly exploit these Siglecs. Human Siglecs have several additional unique and/or polymorphic properties as compared with closely related great apes, changes possibly related to the loss of the sialic acid Neu5Gc, another distinctly human event in sialobiology. Multiple changes in human CD33rSiglecs compared to great apes include many examples of human-specific expression in non-immune cells, coinciding with human-specific diseases involving such cell types. Some Siglec gene polymorphisms have dual consequences—beneficial in a situation but detrimental in another. The association of human Siglec gene polymorphisms with several infectious and non-infectious diseases likely reflects the ongoing competition between the host and microbial pathogens.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9905256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10801116","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}

引用次数: 14