Exosomes: Potential Disease Biomarkers and New Therapeutic Targets

Exosomes are extracellular vesicles released by cells, both constitutively and after cell activation, and are present in different types of biological fluid. Exosomes are involved in the pathogenesis of diseases, such as cancer, neurodegenerative diseases, pregnancy disorders and cardiovascular diseases, and have emerged as potential non-invasive biomarkers for the detection, prognosis and therapeutics of a myriad of diseases. In this review, we describe recent advances related to the regulatory mechanisms of exosome biogenesis, release and molecular composition, as well as their role in health and disease, and their potential use as disease biomarkers and therapeutic targets. In addition, the advantages and disadvantages of their main isolation methods, characterization and cargo analysis, as well as the experimental methods used for exosome-mediated drug delivery, are discussed. Finally, we present potential perspectives for the use of exosomes in future clinical practice.

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Multiplexed imaging of human tuberculosis granulomas uncovers immunoregulatory features conserved across tissue and blood

10.1101/2020.06.08.140426 ◽

2020 ◽

Author(s):

Erin F. McCaffrey ◽

Michele Donato ◽

Leeat Keren ◽

Zhenghao Chen ◽

Megan Fitzpatrick ◽

...

Keyword(s):

Gene Expression ◽

Immune Responses ◽

T Cell Activation ◽

Cell Activation ◽

Immune Cell ◽

Ion Beam ◽

Multiplexed Imaging ◽

Health And Disease ◽

Unique Cell ◽

Potential Use

AbstractTuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that is distinctly characterized by granuloma formation within infected tissues. Granulomas are dynamic and organized immune cell aggregates that limit dissemination, but can also hinder bacterial clearance. Consequently, outcome in TB is influenced by how granuloma structure and composition shift the balance between these two functions. To date, our understanding of what factors drive granuloma function in humans is limited. With this in mind, we used Multiplexed Ion Beam Imaging by Time-of-Flight (MIBI-TOF) to profile 37 proteins in tissues from thirteen patients with active TB disease from the U.S. and South Africa. With this dataset, we constructed a comprehensive tissue atlas where the lineage, functional state, and spatial distribution of 19 unique cell subsets were mapped onto eight phenotypically-distinct granuloma microenvironments. This work revealed an immunosuppressed microenvironment specific to TB granulomas with spatially coordinated co-expression of IDO1 and PD-L1 by myeloid cells and proliferating regulatory T cells. Interestingly, this microenvironment lacked markers consistent with T-cell activation, supporting a myeloid-mediated mechanism of immune suppression. We observed similar trends in gene expression of immunoregulatory proteins in a confirmatory transcriptomic analysis of peripheral blood collected from over 1500 individuals with latent or active TB infection and healthy controls across 29 cohorts spanning 14 countries. Notably, PD-L1 gene expression was found to correlate with TB progression and treatment response, supporting its potential use as a blood-based biomarker. Taken together, this study serves as a framework for leveraging independent cohorts and complementary methodologies to understand how local and systemic immune responses are linked in human health and disease.

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Role of Cardiac MRI in Detecting Familial Hypertrophic Cardiomyopathy: Review

Journal of Clinical and Health Sciences ◽

10.24191/jchs.v1i1.5846 ◽

2016 ◽

Vol 1 (1) ◽

pp. 4

Author(s):

Marymol Koshy ◽

Bushra Johari ◽

Mohd Farhan Hamdan ◽

Mohammad Hanafiah

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Magnetic Resonance ◽

Genetic Disorder ◽

Familial Hypertrophic Cardiomyopathy ◽

Non Invasive ◽

Wide Range ◽

Proper Diagnosis ◽

Magnetic Resonance Imaging Mri ◽

Potential Use

Hypertrophic cardiomyopathy (HCM) is a global disease affecting people of various ethnic origins and both genders. HCM is a genetic disorder with a wide range of symptoms, including the catastrophic presentation of sudden cardiac death. Proper diagnosis and treatment of this disorder can relieve symptoms and prolong life. Non-invasive imaging is essential in diagnosing HCM. We present a review to deliberate the potential use of cardiac magnetic resonance (CMR) imaging in HCM assessment and also identify the risk factors entailed with risk stratification of HCM based on Magnetic Resonance Imaging (MRI).

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Oxidized Haemoglobin–Driven Endothelial Dysfunction and Immune Cell Activation: Novel Therapeutic Targets for Atherosclerosis

Current Medicinal Chemistry ◽

10.2174/09298673113209990162 ◽

2013 ◽

Vol 20 (37) ◽

pp. 4806-4814 ◽

Cited By ~ 8

Author(s):

Brigitta Buttari ◽

Elisabetta Profumo ◽

Rita Businaro ◽

Luciano Saso ◽

Raffaele Capoano ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Cell Activation ◽

Immune Cell ◽

Therapeutic Targets ◽

Immune Cell Activation ◽

Novel Therapeutic

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Non-invasive approaches to functional recovery after spinal cord injury: Therapeutic targets and multimodal device interventions

Experimental Neurology ◽

10.1016/j.expneurol.2021.113612 ◽

2021 ◽

Vol 339 ◽

pp. 113612

Author(s):

Claudio Pizzolato ◽

Mehmet A. Gunduz ◽

Dinesh Palipana ◽

Jingnan Wu ◽

Gary Grant ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Functional Recovery ◽

Therapeutic Targets ◽

Non Invasive ◽

Cord Injury

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Biomechanics of Neutrophil Tethers

Life ◽

10.3390/life11060515 ◽

2021 ◽

Vol 11 (6) ◽

pp. 515

Author(s):

Andrea Cugno ◽

Alex Marki ◽

Klaus Ley

Keyword(s):

Cell Activation ◽

Optical Trap ◽

Biomechanical Properties ◽

Force Microscopy ◽

Advantages And Disadvantages ◽

Atomic Force ◽

Microfluidic Flow ◽

Biomembrane Force Probe ◽

Membrane Reservoir

Leukocytes, including neutrophils, which are propelled by blood flow, can roll on inflamed endothelium using transient bonds between selectins and their ligands, and integrins and their ligands. When such receptor–ligand bonds last long enough, the leukocyte microvilli become extended and eventually form thin, 20 m long tethers. Tether formation can be observed in blood vessels in vivo and in microfluidic flow chambers. Tethers can also be extracted using micropipette aspiration, biomembrane force probe, optical trap, or atomic force microscopy approaches. Here, we review the biomechanical properties of leukocyte tethers as gleaned from such measurements and discuss the advantages and disadvantages of each approach. We also review and discuss viscoelastic models that describe the dependence of tether formation on time, force, rate of loading, and cell activation. We close by emphasizing the need to combine experimental observations with quantitative models and computer simulations to understand how tether formation is affected by membrane tension, membrane reservoir, and interactions of the membrane with the cytoskeleton.

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Adhesion GPCRs in Glioblastoma

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab046 ◽

2021 ◽

Author(s):

Gabriele Stephan ◽

Niklas Ravn-Boess ◽

Dimitris G Placantonakis

Keyword(s):

G Protein ◽

G Protein Coupled Receptors ◽

The Past ◽

Novel Treatment ◽

The Family ◽

Health And Disease ◽

Basic Biology ◽

G Protein Coupled ◽

Potential Use ◽

Receptor Family

Abstract Members of the adhesion family of G protein-coupled receptors (GPCRs) have received attention for their roles in health and disease, including cancer. Over the past decade, several members of the family have been implicated in the pathogenesis of glioblastoma. Here, we discuss the basic biology of adhesion GPCRs and review in detail specific members of the receptor family with known functions in glioblastoma. Finally, we discuss the potential use of adhesion GPCRs as novel treatment targets in neuro-oncology.

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Analytical validation of an automated assay for the measurement of adenosine deaminase (ADA) and its isoenzymes in saliva and a pilot evaluation of their changes in patients with SARS-CoV-2 infection

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2021-0324 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Lorena Franco-Martínez ◽

Fernando Tecles ◽

Alberto Torres-Cantero ◽

Enrique Bernal ◽

Indra San Lázaro ◽

...

Keyword(s):

Adenosine Deaminase ◽

Analytical Validation ◽

Mean Values ◽

Chemical Inactivation ◽

Non Invasive ◽

Automated Assay ◽

Coefficients Of Variation ◽

Recovery Percentage ◽

Triton X ◽

Potential Use

Abstract Objectives The aim of the present study was to validate a commercially available automated assay for the measurement of total adenosine deaminase (tADA) and its isoenzymes (ADA1 and ADA2) in saliva in a fast and accurate way, and evaluate the possible changes of these analytes in individuals with SARS-CoV-2 infection. Methods The validation, in addition to the evaluation of precision and accuracy, included the analysis of the effects of the main procedures that are currently being used for SARS-CoV-2 inactivation in saliva and a pilot study to evaluate the possible changes in salivary tADA and isoenzymes in individuals infected with SARS-CoV-2. Results The automated assay proved to be accurate and precise, with intra- and inter-assay coefficients of variation below 8.2%, linearity under dilution linear regression with R2 close to 1, and recovery percentage between 80 and 120% in all cases. This assay was affected when the sample is treated with heat or SDS for virus inactivation but tolerated Triton X-100 and NP-40. Individuals with SARS-CoV-2 infection (n=71) and who recovered from infection (n=11) had higher mean values of activity of tADA and its isoenzymes than healthy individuals (n=35). Conclusions tADA and its isoenzymes ADA1 and ADA2 can be measured accurately and precisely in saliva samples in a rapid, economical, and reproducible way and can be analyzed after chemical inactivation with Triton X-100 and NP-40. Besides, the changes observed in tADA and isoenzymes in individuals with COVID-19 open the possibility of their potential use as non-invasive biomarkers in this disease.

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In Vivo Imaging of Biodegradable Implants and Related Tissue Biomarkers

Polymers ◽

10.3390/polym13142348 ◽

2021 ◽

Vol 13 (14) ◽

pp. 2348

Author(s):

Leon Riehakainen ◽

Chiara Cavallini ◽

Paolo Armanetti ◽

Daniele Panetta ◽

Davide Caramella ◽

...

Keyword(s):

Imaging Modality ◽

Imaging Techniques ◽

Special Focus ◽

Tissue Remodelling ◽

Biodegradable Implant ◽

Advantages And Disadvantages ◽

Non Invasive ◽

Positron Emission ◽

Longitudinal Imaging

Non-invasive longitudinal imaging of osseointegration of bone implants is essential to ensure a comprehensive, physical and biochemical understanding of the processes related to a successful implant integration and its long-term clinical outcome. This study critically reviews the present imaging techniques that may play a role to assess the initial stability, bone quality and quantity, associated tissue remodelling dependent on implanted material, implantation site (surrounding tissues and placement depth), and biomarkers that may be targeted. An updated list of biodegradable implant materials that have been reported in the literature, from metal, polymer and ceramic categories, is provided with reference to the use of specific imaging modalities (computed tomography, positron emission tomography, ultrasound, photoacoustic and magnetic resonance imaging) suitable for longitudinal and non-invasive imaging in humans. The advantages and disadvantages of the single imaging modality are discussed with a special focus on preclinical imaging for biodegradable implant research. Indeed, the investigation of a new implant commonly requires histological examination, which is invasive and does not allow longitudinal studies, thus requiring a large number of animals for preclinical testing. For this reason, an update of the multimodal and multi-parametric imaging capabilities will be here presented with a specific focus on modern biomaterial research.

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