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Article ; Online: Therapeutic effect of two strategies directed at disruption of pathogenic neutrophil extracellular vesicles in a murine emphysema model.

Genschmer, Kristopher R / Madison, Matthew / Viera, Liliana / Margaroli, Camilla / Gaggar, Amit / Blalock, J Edwin / Russell, Derek W

American journal of physiology. Lung cellular and molecular physiology

2023 Volume 324, Issue 5, Page(s) L694–L699

Abstract: Chronic obstructive pulmonary disease (COPD) is characterized by lung extracellular matrix (ECM) remodeling that contributes to obstruction. This is driven, in part by extracellular vesicles (EVs) from activated neutrophils (PMNs), which express on their ...

Abstract	Chronic obstructive pulmonary disease (COPD) is characterized by lung extracellular matrix (ECM) remodeling that contributes to obstruction. This is driven, in part by extracellular vesicles (EVs) from activated neutrophils (PMNs), which express on their surface an α-1 antitrypsin (AAT) insensitive form of neutrophil elastase (NE). These EVs are predicted to bind to collagen fibers via Mac-1 integrins, during which time NE can enzymatically degrade the collagen. Protamine sulfate (PS), a cationic compound used safely for decades in humans, has been shown, in vitro, to dissociate this NE from the EV surface, rendering it AAT-sensitive. In addition, a nonapeptide inhibitor, MP-9, has been shown to prevent EV association with collagen. We sought to test whether PS, MP-9, or a combination of the two could effectively prevent NE+ EV-driven ECM remodeling in an animal COPD model. EVs were preincubated with PBS, protamine sulfate (25 μM), MP-9 (50 μM), or a combination of PS and MP-9. These were delivered intratracheally to anesthetized female 10- to 12-wk-old A/J mice for a 7-day time period. One group of mice was euthanized and lungs sectioned for morphometry, and the other group was used for live pulmonary function testing. The effect of alveolar destruction by activated neutrophil EVs was abrogated by pretreatment with PS or MP-9. However, in pulmonary function tests, only the PS groups (and combined PS/MP-9 groups) returned pulmonary function to near-control levels. These data presented here offer an insight into the effective use of PS in therapeutic setting for EV-derived alveolar damage.
MeSH term(s)	Humans ; Female ; Mice ; Animals ; Leukocyte Elastase/metabolism ; Neutrophils/metabolism ; Pulmonary Emphysema/metabolism ; Pulmonary Disease, Chronic Obstructive/metabolism ; Collagen/metabolism ; Emphysema ; Extracellular Vesicles/metabolism
Chemical Substances	Leukocyte Elastase (EC 3.4.21.37) ; Collagen (9007-34-5)
Language	English
Publishing date	2023-04-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1013184-x
ISSN	1522-1504 ; 1040-0605
ISSN (online)	1522-1504
ISSN	1040-0605
DOI	10.1152/ajplung.00057.2023
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Article ; Online: An in vivo model for extracellular vesicle-induced emphysema.

Margaroli, Camilla / Madison, Matthew C / Viera, Liliana / Russell, Derek W / Gaggar, Amit / Genschmer, Kristopher R / Blalock, J Edwin

JCI insight

2022 Volume 7, Issue 4

Abstract: Chronic obstructive pulmonary disease (COPD) is a debilitating chronic disease and the third-leading cause of mortality worldwide. It is characterized by airway neutrophilia, promoting tissue injury through release of toxic mediators and proteases. ... ...

Abstract	Chronic obstructive pulmonary disease (COPD) is a debilitating chronic disease and the third-leading cause of mortality worldwide. It is characterized by airway neutrophilia, promoting tissue injury through release of toxic mediators and proteases. Recently, it has been shown that neutrophil-derived extracellular vesicles (EVs) from lungs of patients with COPD can cause a neutrophil elastase-dependent (NE-dependent) COPD-like disease upon transfer to mouse airways. However, in vivo preclinical models elucidating the impact of EVs on disease are lacking, delaying opportunities for therapeutic testing. Here, we developed an in vivo preclinical mouse model of lung EV-induced COPD. EVs from in vivo LPS-activated mouse neutrophils induced COPD-like disease in naive recipients through an α-1 antitrypsin-resistant, NE-dependent mechanism. Together, these results show a key pathogenic and mechanistic role for neutrophil-derived EVs in a mouse model of COPD. Broadly, the in vivo model described herein could be leveraged to develop targeted therapies for severe lung disease.
MeSH term(s)	Animals ; Disease Models, Animal ; Extracellular Vesicles/pathology ; Mice ; Pulmonary Disease, Chronic Obstructive/diagnosis ; Pulmonary Disease, Chronic Obstructive/etiology ; Pulmonary Disease, Chronic Obstructive/metabolism ; Pulmonary Emphysema/complications ; Pulmonary Emphysema/metabolism
Language	English
Publishing date	2022-01-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.153560
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Article ; Online: El laboratorio en Química Orgánica: una propuesta para la promoción de competencias científico-tecnológicas

Viera, Liliana I. / Ramírez, Silvia S. / Fleisner, Ana

Universidad Nacional Autónoma de México, Facultad de Química Educación Química. 2017,

2017

Abstract: From different spaces it has been stated that the training in competences would seem to be the challenge of High Education. In this teaching model, not only is the understanding of the conceptual content of the disciplines important, but also the ... ...

Abstract	From different spaces it has been stated that the training in competences would seem to be the challenge of High Education. In this teaching model, not only is the understanding of the conceptual content of the disciplines important, but also the acquisition of the complex skills needed to develop competently.This paper presents a proposal for the experimental part of a university course of Organic Chemistry based on the approach of teaching by competences. We believe that, through its implementation, competencies such as: organization and decision making, manual skills, investigative procedures and attitudes, conceptual understanding, social attitudes and information management, are promoted. Students must design a work plan whose objective is the isolation and purification of a natural product, using all the theoretical tools studied and the materials and reagents available. Subsequently they must present it in oral and written form, execute it and make a final report (written and oral) in which the results are communicated, analyzed and discussed.The experiences showed a greater motivation of the students and an environment of great potentiality to favor the acquisition of scientific-technological competences. These kinds of experiences are transferable to other disciplines that require experimental work.
Keywords	Química Orgánica ; Laboratorio ; Universidad ; Competencias ; Organic Chemistry ; Laboratory ; University ; Competences
Language	English
Publishing place	Elsevier España, S.L.U.
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	2754135-6
ISSN	1870-8404 ; 0187-893X
ISSN (online)	1870-8404
ISSN	0187-893X
DOI	10.1016/j.eq.2017.04.002
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Temas de química cuántica: análisis de su presentación en libros de texto de química general

Ramirez, Silvia / Fleisner, Ana / Viera, Liliana

Universidad Nacional Autónoma de México, Facultad de Química Educación Química. 2017,

2017

Abstract: College students show serious difficulties in learning chemistry. From research in science teaching, this problem is considered to be multicausal. We will focus on one of the possible intrinsically disciplinary causes. Among the first issues addressed in ...

Abstract	College students show serious difficulties in learning chemistry. From research in science teaching, this problem is considered to be multicausal. We will focus on one of the possible intrinsically disciplinary causes. Among the first issues addressed in basic chemistry courses of scientific/technological careers are those corresponding to quantum chemistry. When the student approaches for the first time these subjects only knows classic contents of physics and chemistry. While many of the terms used in both contexts are the same, the 'world' and 'objects' referred to in classical physics not seem to be the same that those that is cited in chemistry. The fact that it would seem that the quantum chemistry depends on physical models available of the world, it adds the complication of using classical physics concepts in a context in which they no longer seem to have the same meaning.In this paper we analyze the way in which general chemistry textbook introduced the contents of quantum chemistry. Four aspects are considered: epistemologic choice, perspective of approach, use of the history and philosophy of science, and contextualisation of relations between quantum and classical concepts. We conclude that the modes of presentation in the texts do not contribute to a better understanding of the concepts of the discipline, nor of the mode in which the scientific knowledge is developed.
Keywords	Química cuántica ; libros de texto ; meta-disciplinas ; ciencia y tecnología Carreras ; Quantum chemistry ; Textbooks ; Meta-disciplines ; Scientific and technological careers
Language	English
Publishing place	Elsevier España, S.L.U.
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	2754135-6
ISSN	1870-8404 ; 0187-893X
ISSN (online)	1870-8404
ISSN	0187-893X
DOI	10.1016/j.eq.2017.03.002
Database	NAL-Catalogue (AGRICOLA)

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Article: Spatial transcriptomic profiling of coronary endothelial cells in SARS-CoV-2 myocarditis.

Margaroli, Camilla / Benson, Paul / Gastanadui, Maria G / Song, Chunyan / Viera, Liliana / Xing, Dongqi / Wells, J Michael / Patel, Rakesh / Gaggar, Amit / Payne, Gregory A

Frontiers in medicine

2023 Volume 10, Page(s) 1118024

Abstract: Objectives: Our objective was to examine coronary endothelial and myocardial programming in patients with severe COVID-19 utilizing digital spatial transcriptomics.: Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has well- ... ...

Abstract	Objectives: Our objective was to examine coronary endothelial and myocardial programming in patients with severe COVID-19 utilizing digital spatial transcriptomics. Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has well-established links to thrombotic and cardiovascular events. Endothelial cell infection was initially proposed to initiate vascular events; however, this paradigm has sparked growing controversy. The significance of myocardial infection also remains unclear. Methods: Autopsy-derived cardiac tissue from control ( Results: We observed heterogeneous myocardial infection that tended to colocalize with CD31 positive cells within coronary capillaries. Despite these differences, COVID-19 patients displayed a uniform and unique myocardial transcriptional profile independent of local viral burden. Segmentation of tissues directly infected with SARS-CoV-2 showed unique, pro-inflammatory expression profiles including upregulated mediators of viral antigen presentation and immune regulation. Infected cell types appeared to primarily be capillary endothelial cells as differentially expressed genes included endothelial cell markers. However, there was limited differential expression within the endothelium of larger coronary vessels. Conclusion: Our results highlight altered myocardial programming during severe COVID-19 that may in part be associated with capillary endothelial cells. However, similar patterns were not observed in larger vessels, diminishing endotheliitis, and endothelial activation as key drivers of cardiovascular events during COVID-19.
Language	English
Publishing date	2023-03-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2023.1118024
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Article ; Online: A mechanism for matrikine regulation in acute inflammatory lung injury.

Robison, Sarah W / Li, JinDong / Viera, Liliana / Blackburn, Jonathan P / Patel, Rakesh P / Blalock, J Edwin / Gaggar, Amit / Xu, Xin

JCI insight

2021 Volume 6, Issue 7

Abstract: Proline-glycine-proline (PGP) and its acetylated form (Ac-PGP) are neutrophil chemoattractants generated by collagen degradation, and they have been shown to play a role in chronic inflammatory disease. However, the mechanism for matrikine regulation in ... ...

Abstract	Proline-glycine-proline (PGP) and its acetylated form (Ac-PGP) are neutrophil chemoattractants generated by collagen degradation, and they have been shown to play a role in chronic inflammatory disease. However, the mechanism for matrikine regulation in acute inflammation has not been well established. Here, we show that these peptides are actively transported from the lung by the oligopeptide transporter, PEPT2. Following intratracheal instillation of Ac-PGP in a mouse model, there was a rapid decline in concentration of the labeled peptide in the bronchoalveolar lavage (BAL) over time and redistribution to extrapulmonary sites. In vitro knockdown of the PEPT2 transporter in airway epithelia or use of a competitive inhibitor of PEPT2, cefadroxil, significantly reduced uptake of Ac-PGP. Animals that received intratracheal Ac-PGP plus cefadroxil had higher levels of Ac-PGP in BAL and lung tissue. Utilizing an acute LPS-induced lung injury model, we demonstrate that PEPT2 blockade enhanced pulmonary Ac-PGP levels and lung inflammation. We further validated this effect using clinical samples from patients with acute lung injury in coculture with airway epithelia. This is the first study to our knowledge to determine the in vitro and in vivo significance of active matrikine transport as a mechanism of modulating acute inflammation and to demonstrate that it may serve as a potential therapeutic target.
MeSH term(s)	Acute Lung Injury/immunology ; Animals ; Anti-Bacterial Agents/pharmacology ; Biological Transport, Active/immunology ; COVID-19/immunology ; COVID-19/metabolism ; Cefadroxil/pharmacology ; Cells, Cultured ; Chemotactic Factors/immunology ; Chemotactic Factors/pharmacology ; Chemotaxis, Leukocyte/immunology ; Disease Models, Animal ; Extracellular Matrix ; Extracellular Matrix Proteins/metabolism ; Humans ; Inflammation/metabolism ; Mice ; Oligopeptides/immunology ; Oligopeptides/pharmacology ; Proline/analogs & derivatives ; Proline/immunology ; Proline/pharmacology ; Symporters/antagonists & inhibitors ; Symporters/metabolism
Chemical Substances	Anti-Bacterial Agents ; Chemotactic Factors ; Extracellular Matrix Proteins ; Oligopeptides ; Symporters ; hydrogen-coupled oligopeptide transporter PepT2 ; prolyl-glycyl-proline ; Cefadroxil (280111G160) ; Proline (9DLQ4CIU6V)
Language	English
Publishing date	2021-04-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.140750
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Spatial transcriptomic profiling of coronary endothelial cells in SARS-CoV-2 myocarditis.

Margaroli, Camilla / Benson, Paul / Gastanadui, Maria G / Song, Chunyan / Viera, Liliana / Xing, Dongqi / Wells, J Michael / Patel, Rakesh / Gaggar, Amit / Payne, Gregory A

bioRxiv : the preprint server for biology

2022

Abstract	Objectives: Our objective was to examine coronary endothelial and myocardial programming in patients with severe COVID-19 utilizing digital spatial transcriptomics. Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has well-established links to thrombotic and cardiovascular events. Endothelial cell infection was initially proposed to initiate vascular events; however, this paradigm has sparked growing controversy. The significance of myocardial infection also remains unclear. Methods: Autopsy-derived cardiac tissue from control (n = 4) and COVID-19 (n = 8) patients underwent spatial transcriptomic profiling to assess differential expression patterns in myocardial and coronary vascular tissue. Our approach enabled transcriptional profiling Results: We observed heterogeneous myocardial infection that tended to colocalize with CD31 positive cells within coronary capillaries. Despite these differences, COVID-19 patients displayed a uniform and unique myocardial transcriptional profile independent of local viral burden. Segmentation of tissues directly infected with SARS-CoV-2 showed unique, pro-inflammatory expression profiles including upregulated mediators of viral antigen presentation and immune regulation. Infected cell types appeared to primarily be capillary endothelial cells as differentially expressed genes included endothelial cell markers. However, there was limited differential expression within the endothelium of larger coronary vessels. Conclusions: Our results highlight altered myocardial programming during severe COVID-19 that may in part be associated with capillary endothelial cells. However, similar patterns were not observed in larger vessels, diminishing endotheliitis and endothelial activation as key drivers of cardiovascular events during COVID-19. Condensed abstract: SARS-CoV-2 is linked to thrombotic and cardiovascular events; however, the mechanism remains uncertain. Our objective was to examine coronary endothelial and myocardial programming in patients with severe COVID-19 utilizing digital spatial transcriptomics. Autopsy-derived coronary arterial and cardiac tissues from control and COVID-19 patients underwent spatial transcriptomic profiling. Our approach enabled transcriptional profiling List of highlights: SARS-CoV-2 has variable expression patterns within the myocardium of COVID-19 patientsSARS-CoV-2 infection induces a unique myocardial transcriptional programming independent of local viral burdenSARS-CoV-2 myocarditis is predominantly associated with capillaritis, and tissues directly infected with SARS-CoV-2 have unique, pro-inflammatory expression profilesDiffuse endothelial activation of larger coronary vessels was absent, diminishing large artery endotheliitis as a significant contributor to cardiovascular events during COVID-19 infection.
Language	English
Publishing date	2022-09-26
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.09.25.509426
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Article ; Online: Spatial transcriptomic profiling of coronary endothelial cells in SARS-CoV-2 myocarditis

Margaroli, Camilla / Benson, Paul / Gastanadui, Maria G / Song, Chunyan / Viera, Liliana / Xing, Dongqi / Wells, J Michael / Patel, Rakesh / Gaggar, Amit / Payne, Gregory A

bioRxiv

Abstract: Objectives: Our objective was to examine coronary endothelial and myocardial programming in patients with severe COVID-19 utilizing digital spatial transcriptomics. Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has well- ... ...

Abstract	Objectives: Our objective was to examine coronary endothelial and myocardial programming in patients with severe COVID-19 utilizing digital spatial transcriptomics. Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has well-established links to thrombotic and cardiovascular events. Endothelial cell infection was initially proposed to initiate vascular events; however, this paradigm has sparked growing controversy. The significance of myocardial infection also remains unclear. Methods: Autopsy-derived cardiac tissue from control (n = 4) and COVID-19 (n = 8) patients underwent spatial transcriptomic profiling to assess differential expression patterns in myocardial and coronary vascular tissue. Our approach enabled transcriptional profiling in situ with preserved anatomy and unaltered local SARS-CoV-2 expression. In so doing, we examined the paracrine effect of SARS-CoV-2 infection in cardiac tissue. Results: We observed heterogeneous myocardial infection that tended to colocalize with CD31 positive cells within coronary capillaries. Despite these differences, COVID-19 patients displayed a uniform and unique myocardial transcriptional profile independent of local viral burden. Segmentation of tissues directly infected with SARS-CoV-2 showed unique, pro-inflammatory expression profiles including upregulated mediators of viral antigen presentation and immune regulation. Infected cell types appeared to primarily be capillary endothelial cells as differentially expressed genes included endothelial cell markers. However, there was limited differential expression within the endothelium of larger coronary vessels. Conclusions: Our results highlight altered myocardial programming during severe COVID-19 that may in part be associated with capillary endothelial cells. However, similar patterns were not observed in larger vessels, diminishing endotheliitis and endothelial activation as key drivers of cardiovascular events during COVID-19.
Keywords	covid19
Language	English
Publishing date	2022-09-26
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2022.09.25.509426
Database	COVID19

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Article ; Online: Prolyl endopeptidase contributes to early neutrophilic inflammation in acute myocardial transplant rejection.

Payne, Gregory A / Sharma, Nirmal S / Lal, Charitharth V / Song, Chunyan / Guo, Lingling / Margaroli, Camilla / Viera, Liliana / Kumar, Siva / Li, Jindong / Xing, Dongqi / Bosley, Melanie / Xu, Xin / Wells, J Michael / George, James F / Tallaj, Jose / Leesar, Massoud / Blalock, J Edwin / Gaggar, Amit

JCI insight

2021 Volume 6, Issue 6

Abstract: Altered inflammation and tissue remodeling are cardinal features of cardiovascular disease and cardiac transplant rejection. Neutrophils have increasingly been understood to play a critical role in acute rejection and early allograft failure; however, ... ...

Abstract	Altered inflammation and tissue remodeling are cardinal features of cardiovascular disease and cardiac transplant rejection. Neutrophils have increasingly been understood to play a critical role in acute rejection and early allograft failure; however, discrete mechanisms that drive this damage remain poorly understood. Herein, we demonstrate that early acute cardiac rejection increases allograft prolyl endopeptidase (PE) in association with de novo production of the neutrophil proinflammatory matrikine proline-glycine-proline (PGP). In a heterotopic murine heart transplant model, PGP production and PE activity were associated with early neutrophil allograft invasion and allograft failure. Pharmacologic inhibition of PE with Z-Pro-prolinal reduced PGP, attenuated early neutrophil graft invasion, and reduced proinflammatory cytokine expression. Importantly, these changes helped preserve allograft rejection-free survival and function. Notably, within 2 independent patient cohorts, both PGP and PE activity were increased among patients with biopsy-proven rejection. The observed induction of PE and matrikine generation provide a link between neutrophilic inflammation and cardiovascular injury, represent a potential target to reduce allogenic immune responses, and uncover a mechanism of cardiovascular disease that has been previously unrecognized to our knowledge.
MeSH term(s)	Adult ; Aged ; Animals ; Critical Pathways ; Female ; Graft Rejection/immunology ; Heart Transplantation ; Humans ; Male ; Mice ; Middle Aged ; Neutrophils/immunology ; Prolyl Oligopeptidases/metabolism
Chemical Substances	Prolyl Oligopeptidases (EC 3.4.21.26)
Language	English
Publishing date	2021-03-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.139687
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Article ; Online: Neutrophil-targeted, protease-activated pulmonary drug delivery blocks airway and systemic inflammation.

Mejías, Joscelyn C / Forrest, Osric A / Margaroli, Camilla / Frey Rubio, David A / Viera, Liliana / Li, Jindong / Xu, Xin / Gaggar, Amit / Tirouvanziam, Rabindra / Roy, Krishnendu

JCI insight

2019 Volume 4, Issue 23

Abstract: Pulmonary drug delivery presents a unique opportunity to target lower airway inflammation, which is often characterized by the massive recruitment of neutrophils from blood. However, specific therapies are lacking modulation of airway neutrophil function, ...

Abstract	Pulmonary drug delivery presents a unique opportunity to target lower airway inflammation, which is often characterized by the massive recruitment of neutrophils from blood. However, specific therapies are lacking modulation of airway neutrophil function, and difficult challenges must be overcome to achieve therapeutic efficacy against pulmonary inflammation, notably drug hydrophobicity, mucociliary and macrophage-dependent clearance, and high extracellular protease burden. Here, we present a multistage, aerodynamically favorable delivery platform that uses extracellular proteolysis to its advantage to deliver nanoparticle-embedded hydrophobic drugs to neutrophils within the lower airways. Our design consists of a self-regulated nanoparticle-in-microgel system, in which microgel activation is triggered by extracellular elastase (degranulated by inflammatory neutrophils), and nanoparticles are loaded with Nexinhib20, a potent neutrophil degranulation inhibitor. Successful in vivo delivery of Nexinhib20 to the airways and into neutrophils promoted resolution of the inflammatory response by dampening neutrophil recruitment and degranulation, proinflammatory cytokine production in both airway and systemic compartments, as well as the presence of neutrophil-derived pathological extracellular vesicles in the lung fluid. Our findings showcase a new platform that overcomes challenges in pulmonary drug delivery and allows customization to match the proteolytic footprint of given diseases.
MeSH term(s)	Animals ; Bronchoalveolar Lavage Fluid ; Cytokines/metabolism ; Disease Models, Animal ; Drug Delivery Systems/methods ; Female ; Inflammation/drug therapy ; Lung/drug effects ; Lung/pathology ; Macrophages ; Mice ; Mice, Inbred C57BL ; Microgels ; Nanoparticles ; Neutrophil Activation/drug effects ; Neutrophil Infiltration ; Neutrophils/metabolism ; Pancreatic Elastase ; Pneumonia/drug therapy ; Pneumonia/pathology
Chemical Substances	Cytokines ; Microgels ; Pancreatic Elastase (EC 3.4.21.36)
Language	English
Publishing date	2019-12-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.131468
Database	MEDical Literature Analysis and Retrieval System OnLINE

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