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Journal of Cardiovascular Magnetic... Oct 2017Parametric mapping techniques provide a non-invasive tool for quantifying tissue alterations in myocardial disease in those eligible for cardiovascular magnetic...
Clinical recommendations for cardiovascular magnetic resonance mapping of T1, T2, T2* and extracellular volume: A consensus statement by the Society for Cardiovascular Magnetic Resonance (SCMR) endorsed by the European Association for Cardiovascular Imaging (EACVI).
Parametric mapping techniques provide a non-invasive tool for quantifying tissue alterations in myocardial disease in those eligible for cardiovascular magnetic resonance (CMR). Parametric mapping with CMR now permits the routine spatial visualization and quantification of changes in myocardial composition based on changes in T1, T2, and T2*(star) relaxation times and extracellular volume (ECV). These changes include specific disease pathways related to mainly intracellular disturbances of the cardiomyocyte (e.g., iron overload, or glycosphingolipid accumulation in Anderson-Fabry disease); extracellular disturbances in the myocardial interstitium (e.g., myocardial fibrosis or cardiac amyloidosis from accumulation of collagen or amyloid proteins, respectively); or both (myocardial edema with increased intracellular and/or extracellular water). Parametric mapping promises improvements in patient care through advances in quantitative diagnostics, inter- and intra-patient comparability, and relatedly improvements in treatment. There is a multitude of technical approaches and potential applications. This document provides a summary of the existing evidence for the clinical value of parametric mapping in the heart as of mid 2017, and gives recommendations for practical use in different clinical scenarios for scientists, clinicians, and CMR manufacturers.
Topics: Consensus; Europe; Heart; Heart Diseases; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Societies, Medical
PubMed: 28992817
DOI: 10.1186/s12968-017-0389-8 -
Frontiers in Immunology 2022Neutrophil extracellular traps (NETs) are specialized structures formed by neutrophils that were initially found to be important in killing pathogenic bacteria during...
BACKGROUND
Neutrophil extracellular traps (NETs) are specialized structures formed by neutrophils that were initially found to be important in killing pathogenic bacteria during infection. With the development of related research, the relationship between NETs and diseases such as sepsis, cancer, and systemic lupus erythematosus has received close attention. However, there is a lack of reports that comprehensively and objectively present the current status of NETs-related studies. Therefore, this study aims to visually analyze the current status and trends of NETs-related research by means of bibliometrics and knowledge mapping.
METHODS
NETs-related articles and reviews were retrieved using the Web of Science core collection subject search, and bibliometric analysis was performed in Excel 365, CiteSpace, VOSviewer, and Bibliometrix (R-Tool of R-Studio).
RESULTS
A total of 4866 publications from 2004 to 2022 were included in the bibliometric analysis. The number of publications shows an increasing trend from year to year. Collaborative network analysis shows that the United States and Germany are the most influential countries in this field, with the highest number of publications and citations. The journal with the most publications is Frontiers in Immunology. Brinkmann Volker is an authoritative author in this field, and his publication "Neutrophil extracellular traps kill bacteria" is the most frequently cited. The literature and keyword analysis shows that the relationship between NETs and diseases (hematological diseases, sepsis, cancer, etc.) and cell death (apoptosis, necroptosis, pyroptosis, etc.) is a popular research topic. Currently, NETs and SARS-CoV-2-related studies are at the forefront of the field.
CONCLUSION
This study is the first to visualize the research in NETs-related fields using bibliometric methods, revealing the trends and frontiers of NETs research. This study will provide valuable references for scholars to find research focus questions and partners.
Topics: Humans; United States; Extracellular Traps; SARS-CoV-2; COVID-19; Bibliometrics; Sepsis; Neoplasms
PubMed: 36341351
DOI: 10.3389/fimmu.2022.1025861 -
Nature Communications Feb 2022During decidualization in rodents, uterine stroma undergoes extensive reprograming into distinct cells, forming the discrete regions defined as the primary decidual zone...
During decidualization in rodents, uterine stroma undergoes extensive reprograming into distinct cells, forming the discrete regions defined as the primary decidual zone (PDZ), the secondary decidual zone (SDZ) and the layer of undifferentiated stromal cells respectively. Here we show that uterine deletion of Men1, a member of the histone H3K4 methyltransferase complex, disrupts the terminal differentiation of stroma, resulting in chaotic decidualization and pregnancy failure. Genome-wide epigenetic profile reveals that Men1 binding in chromatin recapitulates H3K4me3 distribution. Further transcriptomic investigation demonstrates that Men1 directly regulates the expression of PTX3, an extra-cellular trap for FGF2 in decidual cells. Decreased Ptx3 upon Men1 ablation leads to aberrant activation of ERK1/2 in the SDZ due to the unrestrained FGF2 signal emanated from undifferentiated stromal cells, which blunt BMP2 induction and decidualization. In brief, our study provides genetic and molecular mechanisms for epigenetic rewiring mediated decidual regionalization by Men1 and sheds new light on pregnancy maintenance.
Topics: C-Reactive Protein; Decidua; Embryo Implantation; Female; Fibroblast Growth Factor 2; Humans; Pregnancy; Serum Amyloid P-Component; Signal Transduction; Stromal Cells; Transcription Factors; Uterus
PubMed: 35194044
DOI: 10.1038/s41467-022-28657-2 -
The Journal of Neuroscience : the... Jun 2018Transporter-mediated glutamate uptake plays an essential role in shaping synaptic neurotransmission. The rapid removal of synaptically released glutamate ensures the...
Transporter-mediated glutamate uptake plays an essential role in shaping synaptic neurotransmission. The rapid removal of synaptically released glutamate ensures the high temporal dynamics characteristic of fast excitatory chemical neurotransmission and prevents the overexcitation of extrasynaptic NMDA receptors that have been implicated in synaptic plasticity impairments and cell death. Despite clear regional differences in plasticity and excitotoxic thresholds, few studies have compared extracellular glutamate dynamics across different brain regions and in response to a range of neural activity including plasticity-inducing stimuli. Here, we used the rapid extracellular fluorescent glutamate sensor iGluSnFR (intensity-based glutamate-sensing fluorescent reporter) and high-speed imaging (205 frames per second) to quantify relative differences in glutamate clearance rates over a wide range of presynaptic activity in the hippocampus, cortex, and striatum of male C57/BL6NCrl mice. We found that the hippocampus was significantly more efficient than the cortex and striatum at clearing synaptically released glutamate and that this efficiency could be attributed, at least in part, to faster glutamate diffusion away from the release site. In addition, we found that pharmacological inhibition of GLT-1, the brain's most abundant glutamate transporter, slowed clearance rates to only a fraction (∼20-25%) of the effect induced by nonselective transporter blockade, regardless of the brain region and the duration of presynaptic activity. In all, our data reveal clear regional differences in glutamate dynamics after neural activity and suggest that non-GLT-1 transporters can make a large contribution to the rate of glutamate clearance in the hippocampus, cortex, and striatum. Glutamate is the brain's most abundant neurotransmitter, and although essential for rapid cell-cell communication, too much glutamate can negatively impact cellular health. Extracellular glutamate levels are tightly regulated by membrane-bound transporters that rapidly remove the glutamate that is released during neural activity, thereby shaping both the spatial and temporal dynamics of excitatory neurotransmission. Using high-speed imaging of an optical sensor of extracellular glutamate, we show that glutamate dynamics vary widely from one brain region to the next and are highly dependent on the duration of synaptic activity. Our data demonstrate the heterogeneous nature of glutamate regulation in the brain and suggest that such regional differences can dramatically affect both the localization and duration of postsynaptic receptor activation during synaptic neurotransmission.
Topics: Amino Acid Transport System X-AG; Animals; Brain; Glutamic Acid; Male; Mice; Mice, Inbred C57BL; Synaptic Transmission
PubMed: 29760178
DOI: 10.1523/JNEUROSCI.3213-17.2018 -
Clinical and Translational Medicine Feb 2022Vascular calcification is a prominent feature of late-stage diabetes, renal and cardiovascular disease (CVD), and has been linked to adverse events. Recent studies in... (Observational Study)
Observational Study
RATIONALE
Vascular calcification is a prominent feature of late-stage diabetes, renal and cardiovascular disease (CVD), and has been linked to adverse events. Recent studies in patients reported that plasma levels of osteomodulin (OMD), a proteoglycan involved in bone mineralisation, associate with diabetes and CVD. We hypothesised that OMD could be implicated in these diseases via vascular calcification as a common underlying factor and aimed to investigate its role in this context.
METHODS AND RESULTS
In patients with chronic kidney disease, plasma OMD levels correlated with markers of inflammation and bone turnover, with the protein present in calcified arterial media. Plasma OMD also associated with cardiac calcification and the protein was detected in calcified valve leaflets by immunohistochemistry. In patients with carotid atherosclerosis, circulating OMD was increased in association with plaque calcification as assessed by computed tomography. Transcriptomic and proteomic data showed that OMD was upregulated in atherosclerotic compared to control arteries, particularly in calcified plaques, where OMD expression correlated positively with markers of smooth muscle cells (SMCs), osteoblasts and glycoproteins. Immunostaining confirmed that OMD was abundantly present in calcified plaques, localised to extracellular matrix and regions rich in α-SMA cells. In vivo, OMD was enriched in SMCs around calcified nodules in aortic media of nephrectomised rats and in plaques from ApoE mice on warfarin. In vitro experiments revealed that OMD mRNA was upregulated in SMCs stimulated with IFNγ, BMP2, TGFβ1, phosphate and β-glycerophosphate, and by administration of recombinant human OMD protein (rhOMD). Mechanistically, addition of rhOMD repressed the calcification process of SMCs treated with phosphate by maintaining their contractile phenotype along with enriched matrix organisation, thereby attenuating SMC osteoblastic transformation. Mechanistically, the role of OMD is exerted likely through its link with SMAD3 and TGFB1 signalling, and interplay with BMP2 in vascular tissues.
CONCLUSION
We report a consistent association of both circulating and tissue OMD levels with cardiovascular calcification, highlighting the potential of OMD as a clinical biomarker. OMD was localised in medial and intimal α-SMA regions of calcified cardiovascular tissues, induced by pro-inflammatory and pro-osteogenic stimuli, while the presence of OMD in extracellular environment attenuated SMC calcification.
Topics: Analysis of Variance; Cohort Studies; Cross-Sectional Studies; Extracellular Matrix Proteins; Humans; Linear Models; Muscle, Smooth; Netherlands; Osteogenesis; Prospective Studies; Proteoglycans; Statistics, Nonparametric; Sweden; Vascular Calcification
PubMed: 35184400
DOI: 10.1002/ctm2.682 -
Journal of Extracellular Vesicles Feb 2023Extracellular vesicles (EVs) carry diverse bioactive components including nucleic acids, proteins, lipids and metabolites that play versatile roles in intercellular and... (Review)
Review
Extracellular vesicles (EVs) carry diverse bioactive components including nucleic acids, proteins, lipids and metabolites that play versatile roles in intercellular and interorgan communication. The capability to modulate their stability, tissue-specific targeting and cargo render EVs as promising nanotherapeutics for treating heart, lung, blood and sleep (HLBS) diseases. However, current limitations in large-scale manufacturing of therapeutic-grade EVs, and knowledge gaps in EV biogenesis and heterogeneity pose significant challenges in their clinical application as diagnostics or therapeutics for HLBS diseases. To address these challenges, a strategic workshop with multidisciplinary experts in EV biology and U.S. Food and Drug Administration (USFDA) officials was convened by the National Heart, Lung and Blood Institute. The presentations and discussions were focused on summarizing the current state of science and technology for engineering therapeutic EVs for HLBS diseases, identifying critical knowledge gaps and regulatory challenges and suggesting potential solutions to promulgate translation of therapeutic EVs to the clinic. Benchmarks to meet the critical quality attributes set by the USFDA for other cell-based therapeutics were discussed. Development of novel strategies and approaches for scaling-up EV production and the quality control/quality analysis (QC/QA) of EV-based therapeutics were recognized as the necessary milestones for future investigations.
Topics: United States; Extracellular Vesicles; Cell Communication; Nucleic Acids; Lung; Sleep
PubMed: 36775986
DOI: 10.1002/jev2.12305 -
Acta Biomaterialia Sep 2023Decellularized lung scaffolds and hydrogels are increasingly being utilized in ex vivo lung bioengineering. However, the lung is a regionally heterogenous organ with...
Decellularized lung scaffolds and hydrogels are increasingly being utilized in ex vivo lung bioengineering. However, the lung is a regionally heterogenous organ with proximal and distal airway and vascular compartments of different structures and functions that may be altered as part of disease pathogenesis. We previously described decellularized normal whole human lung extracellular matrix (ECM) glycosaminoglycan (GAG) composition and functional ability to bind matrix-associated growth factors. We now determine differential GAG composition and function in airway, vascular, and alveolar-enriched regions of decellularized lungs obtained from normal, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF) patients. Significant differences were observed in heparan sulfate (HS), chondroitin sulfate (CS), and hyaluronic acid (HA) content and CS/HS compositions between both different lung regions and between normal and diseased lungs. Surface plasmon resonance demonstrated that HS and CS from decellularized normal and COPD lungs similarly bound fibroblast growth factor 2, but that binding was decreased in decellularized IPF lungs. Binding of transforming growth factor β to CS was similar in all three groups but binding to HS was decreased in IPF compared to normal and COPD lungs. In addition, cytokines dissociate faster from the IPF GAGs than their counterparts. The differences in cytokine binding features of IPF GAGs may result from different disaccharide compositions. The purified HS from IPF lung is less sulfated than that from other lungs, and the CS from IPF contains more 6-O-sulfated disaccharide. These observations provide further information for understanding functional roles of ECM GAGs in lung function and disease. STATEMENT OF SIGNIFICANCE: Lung transplantation remains limited due to donor organ availability and need for life-long immunosuppressive medication. One solution, the ex vivo bioengineering of lungs via de- and recellularization has not yet led to a fully functional organ. Notably, the role of glycosaminoglycans (GAGs) remaining in decellularized lung scaffolds is poorly understood despite their important effects on cell behaviors. We have previously investigated residual GAG content of native and decellularized lungs and their respective functionality, and role during scaffold recellularization. We now present a detailed characterization of GAG and GAG chain content and function in different anatomical regions of normal diseased human lungs. These are novel and important observations that further expand knowledge about functional GAG roles in lung biology and disease.
Topics: Humans; Glycosaminoglycans; Lung; Chondroitin Sulfates; Pulmonary Disease, Chronic Obstructive; Extracellular Matrix; Disaccharides
PubMed: 37433361
DOI: 10.1016/j.actbio.2023.06.043 -
Plant Signaling & Behavior Dec 2021The global electric circuit and the marine layer in coastal regions result in the presence of atmospheric negative polarity ions within the canopy of plants. This leads...
The global electric circuit and the marine layer in coastal regions result in the presence of atmospheric negative polarity ions within the canopy of plants. This leads to the hypothesis:In the presence of negative polarity atmospheric ions plants activate a plant wide system to absorb and utilize these negative polarity ions.This plant wide system, termed Extracellular Transport System (ETS), is focused on nitrate movement. The object of this paper is to verify the existence of ETS by characterizing 1) how ETS absorbs ion from the atmosphere and 2) within the plant how ETS moves ions from source to destination. Over the past 2-years characteristics of ETS were examined in pecans, pistachios, lemons, wine grapes, cotton, corn, avocados and chili peppers in production agriculture fields in Arizona and California. Nitrate movement was separated into three physical locations: Location I, in the atmosphere outside the plant; Location II, in the interfacial volume between the atmosphere and the plant surface; Location III, in the plant itself. The paper is divided into three parts. Each part is concerned with a particular location of nitrate movement. The major tool of verification is presentation of simultaneous patterns of nitrate ion arrival rate on a simulated plant surface and subsequent movement of nitrate within the extracellular region of the plant. Use of this tool is illustrated in corn, lemons, chili peppers and avocados.A base functionality of ETS has been developed: ETS is a transient, plant wide system wherein 1) nitrate ions are putatively absorbed by a variety of epidermal structures including trichomes and transferred into the extracellular region, 2) hydrated pathways are produced in the extracellular region through which these nitrate ions pass 3) electrical potential gradients are created in the extracellular region which provide a force field to provoke movement of nitrate ions through these pathways. Anthropomorphic climate has three dimensions: light, temperature and moisture. Phytomorphic climate has five dimensions: light, temperature, moisture, earth tides and atmospheric ion presence. ETS is a natural adaptation of plants to the transient nature of atmospheric negative polarity ion presence. It provides a mechanism for plants to utilize this ubiquitous and renewable source of nitrate.
Topics: Atmosphere; Nitrates; Plants
PubMed: 34554051
DOI: 10.1080/15592324.2021.1890431 -
Cell Apr 2020Pioneering research from Mina Bissell established the "Dynamic-Reciprocity" view of biology in which there is a bidirectional interaction between cells and their...
Pioneering research from Mina Bissell established the "Dynamic-Reciprocity" view of biology in which there is a bidirectional interaction between cells and their microenvironment. Her revolutionary work showed that extracellular matrix signaling and microenvironment impact gene expression, taking cancer research beyond genetics. For these contributions, she is the recipient of the 2020 Canada Gairdner International Award. Growing up in a well-educated family in Iran, Mina liked to ask many "why" questions. She spoke with Cell editor Miao-Chih Tsai about how she tackles scientific questions and life challenges. Excerpts from this conversation are presented below, and the full conversation is available with the article online.
Topics: Awards and Prizes; Canada; Communication; Extracellular Matrix; Female; History, 20th Century; History, 21st Century; Humans
PubMed: 32234522
DOI: 10.1016/j.cell.2020.03.028