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Article ; Online: Cardiac Repair: The Intricate Crosstalk between the Epicardium and the Myocardium.

Pellegrini, Laura / Foglio, Eleonora / Pontemezzo, Elena / Germani, Antonia / Russo, Matteo Antonio / Limana, Federica

2020 Volume 15, Issue 8, Page(s) 661–673

Abstract: Background: Substantial evidences support the hypothesis that the epicardium has a role in cardiac repair and regeneration in part providing, by epithelial to mesenchymal transition (EMT), progenitor cells that differentiate into cardiac cell types and ... ...

Abstract	Background: Substantial evidences support the hypothesis that the epicardium has a role in cardiac repair and regeneration in part providing, by epithelial to mesenchymal transition (EMT), progenitor cells that differentiate into cardiac cell types and in part releasing paracrine factors that contribute to cardiac repair. Besides cell contribution, a significant paracrine communication occurs between the epicardium and the myocardium that improves the whole regenerative response. Signaling pathways underlying this communication are multiple as well as soluble factors involved in cardiac repair and secreted both by myocardial and epicardial cells. Most recently, extracellular vesicles, i.e. exosomes, that accumulate in the pericardial fluid (PF) and are able to transport bioactive molecules (cytosolic proteins, mRNAs, miRNAs and other non-coding RNAs), have been also identified as potential mediators of epicardial-mediated repair following myocardial injury. Conclusion: This mini-review provides an overview of the epicardial-myocardial signaling in regulating cardiac repair in ischemic heart diseases. Indeed, a detailed understanding of the crosstalk between myocardial and epicardial cells and how paracrine mechanisms are involved in the context of ischemic heart diseases would be of tremendous help in developing novel therapeutic approaches to promote cardiomyocytes survival and heart regeneration following myocardial infarction (MI).
MeSH term(s)	Epithelial-Mesenchymal Transition ; Humans ; Myocardial Infarction ; Myocardium ; Myocytes, Cardiac ; Pericardium/physiology ; Signal Transduction
Language	English
Publishing date	2020-02-17
Publishing country	United Arab Emirates
Document type	Journal Article ; Review
ZDB-ID	2251937-3
ISSN	2212-3946 ; 1574-888X
ISSN (online)	2212-3946
ISSN	1574-888X
DOI	10.2174/1574888X15666200219105448
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Article ; Online: HMGB1-mediated apoptosis and autophagy in ischemic heart diseases.

Foglio, Eleonora / Pellegrini, Laura / Germani, Antonia / Russo, Matteo Antonio / Limana, Federica

Vascular biology (Bristol, England)

2019 Volume 1, Issue 1, Page(s) H89–H96

Abstract: Acute myocardial infarction (MI) and its consequences are the most common and lethal heart syndromes worldwide and represent a significant health problem. Following MI, apoptosis has been generally seen as the major contributor of the cardiomyocyte fate ... ...

Abstract	Acute myocardial infarction (MI) and its consequences are the most common and lethal heart syndromes worldwide and represent a significant health problem. Following MI, apoptosis has been generally seen as the major contributor of the cardiomyocyte fate and of the resultant myocardial remodeling. However, in recent years, it has been discovered that, following MI, cardiomyocytes could activate autophagy in an attempt to protect themselves against ischemic stress and to preserve cardiac function. Although initially seen as two completely separate responses, recent works have highlighted the intertwined crosstalk between apoptosis and autophagy. Numerous researches have tried to unveil the mechanisms and the molecular players involved in this phenomenon and have identified in high-mobility group box 1 (HMGB1), a highly conserved non-histone nuclear protein with important roles in the heart, one of the major regulator. Thus, the aim of this mini review is to discuss how HMGB1 regulates these two responses in ischemic heart diseases. Indeed, a detailed understanding of the crosstalk between apoptosis and autophagy in these pathologies and how HMGB1 regulates them would be of tremendous help in developing novel therapeutic approaches aimed to promote cardiomyocyte survival and to diminish tissue injury following MI.
Language	English
Publishing date	2019-08-12
Publishing country	England
Document type	Journal Article ; Review
ISSN	2516-5658
ISSN (online)	2516-5658
DOI	10.1530/VB-19-0013
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Article ; Online: HMGB1 and repair: focus on the heart.

Pellegrini, Laura / Foglio, Eleonora / Pontemezzo, Elena / Germani, Antonia / Russo, Matteo Antonio / Limana, Federica

Pharmacology & therapeutics

2018 Volume 196, Page(s) 160–182

Abstract: High-mobility group box 1 (HMGB1) is one of the most abundant proteins in eukaryotes and the best characterized damage-associated molecular pattern (DAMP). The biological activities of HMGB1 depend on its subcellular location, context and post- ... ...

Abstract	High-mobility group box 1 (HMGB1) is one of the most abundant proteins in eukaryotes and the best characterized damage-associated molecular pattern (DAMP). The biological activities of HMGB1 depend on its subcellular location, context and post-translational modifications. Inside the nucleus, HMGB1 is engaged in many DNA events such as DNA repair, transcription regulation and genome stability; in the cytoplasm, its main function is to regulate the autophagic flux while in the extracellular environment, it possesses more complicated functions and it is involved in a large variety of different processes such as inflammation, migration, invasion, proliferation, differentiation and tissue regeneration. Due to this pleiotropy, the role of HMGB1 has been vastly investigated in various pathological diseases and a large number of studies have explored its function in cardiovascular pathologies. However, in this contest, the precise mechanism of action of HMGB1 and its therapeutic potential are still very controversial since is debated whether HMGB1 is involved in tissue damage or plays a role in tissue repair and regeneration. The main focus of this review is to provide an overview of the effects of HMGB1 in different ischemic heart diseases and to discuss its functions in these pathological conditions.
MeSH term(s)	Animals ; HMGB1 Protein/metabolism ; Heart Diseases/metabolism ; Heart Diseases/pathology ; Humans ; Myocardium/metabolism ; Myocardium/pathology
Chemical Substances	HMGB1 Protein
Language	English
Publishing date	2018-12-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	194735-7
ISSN	1879-016X ; 0163-7258
ISSN (online)	1879-016X
ISSN	0163-7258
DOI	10.1016/j.pharmthera.2018.12.005
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Zs.A 1183: Show issues

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Article ; Online: Transcriptomic Signatures of MSI-High Metastatic Colorectal Cancer Predict Efficacy of Immune Checkpoint Inhibitors.

Clinical cancer research : an official journal of the American Association for Cancer Research

2023 Volume 29, Issue 18, Page(s) 3771–3778

Abstract: Purpose: Microsatellite instability (MSI) is currently the only predictive biomarker of efficacy of immune checkpoint inhibitors (ICI) in metastatic colorectal cancers (mCRC). However, 10% to 40% of patients with MSI mCRC will experience a primary ... ...

Abstract	Purpose: Microsatellite instability (MSI) is currently the only predictive biomarker of efficacy of immune checkpoint inhibitors (ICI) in metastatic colorectal cancers (mCRC). However, 10% to 40% of patients with MSI mCRC will experience a primary resistance to ICI. Experimental design: In two cohorts of patients with MSI mCRC treated with ICI (exploratory, N = 103; validation, N = 35), 3' RNA sequencing was performed from primary tumors. Previously described single-cell transcriptomic signatures of tumor microenvironment (TME) were analyzed. Results: In the exploratory cohort, the unsupervised clustering allowed the identification of three clusters of tumors with distinct transcriptional profiles: cluster A ("stromalHIGH-proliferationLOW"), cluster B ("stromalHIGH-proliferationMED"), and cluster C ("stromalLOW-proliferationHIGH"), with an enrichment of patients progressing at first disease assessment under ICI in cluster A (30% vs. 12% in cluster B and 8.1% in cluster C; P = 0.074). Progression-free survival (PFS) was also significantly shorter in patients belonging to cluster A, compared with clusters B or C (P < 0.001) with 2-year PFS rates of 33.5%, 80.5%, and 78.3%, respectively. In multivariate analysis, PFS was still significantly longer in patients belonging to cluster B [HR, 0.19; 95% confidence interval (CI), 0.08-0.45; P < 0.001] and cluster C (HR, 0.25; 95% CI, 0.10-0.59; P = 0.02), compared with patients belonging to cluster A. The association of this clustering with PFS under ICI was confirmed in the validation cohort. PFS related to non-ICI-based regimens was not significantly different according to cluster. Conclusions: This unsupervised transcriptomic classification identified three groups of MSI mCRCs with different compositions of TME cells and proliferative capacities of TME/tumor cells. The "stromalHIGH-proliferationLOW" cluster is associated with a poorer prognosis with ICI treatment.
MeSH term(s)	Humans ; Immune Checkpoint Inhibitors/pharmacology ; Immune Checkpoint Inhibitors/therapeutic use ; Transcriptome ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Colonic Neoplasms ; Biomarkers ; Microsatellite Instability ; Tumor Microenvironment/genetics
Chemical Substances	Immune Checkpoint Inhibitors ; Biomarkers
Language	English
Publishing date	2023-07-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-22-3964
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Zs.A 4223: Show issues

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Article ; Online: Comment on: Biscetti et al. (2010) High-mobility group box-1 protein promotes angiogenesis after peripheral ischemia in diabetic mice through a VEGF-dependent mechanism. Diabetes;59:1496-1505.

Germani, Antonia / Capogrossi, Maurizio C

Diabetes

2010 Volume 59, Issue 7, Page(s) e7; author reply e8

MeSH term(s)	Animals ; Diabetes Mellitus, Experimental/metabolism ; HMGB1 Protein/metabolism ; Ischemia/physiopathology ; Mice ; Neovascularization, Physiologic/physiology ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	HMGB1 Protein ; Vascular Endothelial Growth Factor A
Language	English
Publishing date	2010-07
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	80085-5
ISSN	1939-327X ; 0012-1797
ISSN (online)	1939-327X
ISSN	0012-1797
DOI	10.2337/db10-0445
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Article ; Online: miR-200c-3p Regulates Epitelial-to-Mesenchymal Transition in Epicardial Mesothelial Cells by Targeting Epicardial Follistatin-Related Protein 1.

Pontemezzo, Elena / Foglio, Eleonora / Vernucci, Enza / Magenta, Alessandra / D'Agostino, Marco / Sileno, Sara / Astanina, Elena / Bussolino, Federico / Pellegrini, Laura / Germani, Antonia / Russo, Matteo Antonio / Limana, Federica

International journal of molecular sciences

2021 Volume 22, Issue 9

Abstract: Recent findings suggest that epithelial to mesenchymal transition (EMT), a key step during heart development, is involved in cardiac tissue repair following myocardial infarction (MI). MicroRNAs (miRNAs) act as key regulators in EMT processes; however, ... ...

Abstract	Recent findings suggest that epithelial to mesenchymal transition (EMT), a key step during heart development, is involved in cardiac tissue repair following myocardial infarction (MI). MicroRNAs (miRNAs) act as key regulators in EMT processes; however, the mechanisms by which miRNAs target epicardial EMT remain largely unknown. Here, by using an
MeSH term(s)	Animals ; Biomarkers/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Epithelium/metabolism ; Female ; Follistatin-Related Proteins/metabolism ; Mesoderm/pathology ; Mice, Inbred C57BL ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Pericardium/pathology ; Transforming Growth Factor beta1/pharmacology ; Mice
Chemical Substances	Biomarkers ; Follistatin-Related Proteins ; Fstl1 protein, mouse ; MicroRNAs ; Mirn200 microRNA, mouse ; Transforming Growth Factor beta1
Language	English
Publishing date	2021-05-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22094971
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Article ; Online: The Nucleolar Protein Nucleophosmin Is Physiologically Secreted by Endothelial Cells in Response to Stress Exerting Proangiogenic Activity Both In Vitro and In Vivo.

Di Carlo, Anna / Beji, Sara / Palmerio, Silvia / Picozza, Mario / D'Agostino, Marco / Petrozza, Vincenzo / Melchionna, Roberta / Germani, Antonia / Magenta, Alessandra / De Falco, Elena / Avitabile, Daniele

International journal of molecular sciences

2021 Volume 22, Issue 7

Abstract: Nucleophosmin (NPM), a nucleolar multifunctional phosphoprotein, acts as a stress sensor in different cell types. NPM can be actively secreted by inflammatory cells, however its biology on endothelium remains unexplored. In this study, we show for the ... ...

Abstract	Nucleophosmin (NPM), a nucleolar multifunctional phosphoprotein, acts as a stress sensor in different cell types. NPM can be actively secreted by inflammatory cells, however its biology on endothelium remains unexplored. In this study, we show for the first time that NPM is secreted by human vein endothelial cells (HUVEC) in the early response to serum deprivation and that NPM acts as a pro-inflammatory and angiogenic molecule both in vitro and in vivo. Accordingly, 24 h of serum starvation condition induced NPM relocalization from the nucleus to cytoplasm. Interestingly, NPM was increasingly excreted in HUVEC-derived conditioned media in a time dependent fashion upon stress conditions up to 24 h. The secretion of NPM was unrelated to cell necrosis within 24 h. The treatment with exogenous and recombinant NPM (rNPM) enhanced migration as well as the Intercellular Adhesion Molecule 1 (ICAM-1) but not Vascular cell adhesion protein 1 (VCAM-1) expression and it did not affect cell proliferation. Notably, in vitro tube formation by Matrigel assay was significantly increased in HUVEC treated with rNPM compared to controls. This result was confirmed by the in vivo injection of Matrigel plug assay upon stimulation with rNPM, displaying significant enhanced number of functional capillaries in the plugs. The stimulation with rNPM in HUVEC was also associated to the increased expression of master genes regulating angiogenesis and migration, including Vascular Endothelial Growth Factor-A (
MeSH term(s)	Endothelial Cells/physiology ; Human Umbilical Vein Endothelial Cells ; Humans ; Neovascularization, Pathologic ; Nuclear Proteins/metabolism ; Stress, Physiological
Chemical Substances	Nuclear Proteins ; nucleophosmin (117896-08-9)
Language	English
Publishing date	2021-04-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22073672
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Article ; Online: PLURALIDADE E MULTIDIMENSIONALIDADEDO SUJEITO E DE SUAS ESPACIALIDADES:DESAFIOS EPISTEMOLÓGICO NA ANÁLISE GEOGRÁFICA

Cicilian Luiza Lowen Sahr / Catia Antonia da Silva / Guiomar Inez Germani

Revista da ANPEGE, Vol 12, Iss 18, Pp 117-

2017 Volume 136

Abstract: O presente artigo analisa o debate empreendido no Grupo de Trabalho “Espaço, Cultura e Diferença: As dimensões étnicas, sociais e ambientais e suas significações” do Enanpege, realizado em 2015 em Presidente Prudente (SP). O desafio a que o grupo se ... ...

Abstract	O presente artigo analisa o debate empreendido no Grupo de Trabalho “Espaço, Cultura e Diferença: As dimensões étnicas, sociais e ambientais e suas significações” do Enanpege, realizado em 2015 em Presidente Prudente (SP). O desafio a que o grupo se propõe refere-se à compreensão de sujeitos definidos a partir de diferenças étnicas e de classe, os quais produzem espacialidades distintas, em geral, em contextos ambientais e sociais diversos. Tal desafio se inscreve no reconhecimento da pluralidade e multidimensionalidade do sujeito, bem como, de seus lugares e territórios. São analisados grupos indígenas, quilombolas, negros, pescadores artesanais, migrantes, camponeses, dentre outros segmentos socialmente discriminados e vulneráveis. Espacialidades diferenciadas e desiguais também refletem, por vezes, formas de segregação, estas produzidas a partir de injustiças e da negação de direitos.
Keywords	Geography (General) ; G1-922
Language	Portuguese
Publishing date	2017-06-01T00:00:00Z
Publisher	Universidade Federal da Grande Dourados
Document type	Article ; Online
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Article ; Online: Naturally Adipose Stromal Cell-Enriched Fat Graft: Comparative Polychromatic Flow Cytometry Study of Fat Harvested by Barbed or Blunt Multihole Cannula.

Caggiati, Alessio / Germani, Antonia / Di Carlo, Anna / Borsellino, Giovanna / Capogrossi, Maurizio C / Picozza, Mario

Aesthetic surgery journal

2017 Volume 37, Issue 5, Page(s) 591–602

Abstract: Background: Fat grafts enriched with cells of the stromal vascular fraction (SVF), especially adipose-derived stromal cells (ASCs), exhibit significantly improved retention over non enriched, plain fat. Different types of liposuction cannulae may yield ... ...

Abstract	Background: Fat grafts enriched with cells of the stromal vascular fraction (SVF), especially adipose-derived stromal cells (ASCs), exhibit significantly improved retention over non enriched, plain fat. Different types of liposuction cannulae may yield lipoaspirates with different subpopulations of cells. Moreover, preparation of adipose tissue for transplantation typically involves centrifugation, which creates a density gradient of fat. Objectives: The authors sought to determine whether liposuction with a barbed or smooth cannula altered the enrichment of the SVF, and specifically ASCs, in low-density (LD) and high-density (HD) fractions of centrifuged adipose tissue. Methods: Fat was harvested from 2 abdominal sites of 5 healthy women with a barbed or smooth multihole blunt-end cannula. After centrifugation, LD and HD fat fractions were digested with collagenase and analyzed by polychromatic flow cytometry to identify and enumerate distinct populations of cells. Results: Overall cell yield and the number of immune cells were consistently higher in HD fractions than in LD fractions, regardless of the cannula employed. More living cells, and specifically more ASCs, populated the HD fractions of lipoaspirates obtained with a barbed cannula than with a smooth cannula. Conclusions: In this study, lipoaspiration with a barbed cannula and isolation of the HD layer of centrifuged adipose tissue yielded maximal amounts of SVF cells, including ASCs.
MeSH term(s)	Adipose Tissue/cytology ; Adipose Tissue/transplantation ; Adult ; Cannula ; Cell Separation/methods ; Centrifugation ; Female ; Flow Cytometry/methods ; Humans ; Lipectomy/instrumentation ; Lipectomy/methods ; Middle Aged ; Stromal Cells/transplantation ; Tissue and Organ Harvesting/instrumentation ; Tissue and Organ Harvesting/methods ; Transplants/cytology
Language	English
Publishing date	2017--01
Publishing country	England
Document type	Comparative Study ; Journal Article
ZDB-ID	2087022-X
ISSN	1527-330X ; 1090-820X ; 1084-0761
ISSN (online)	1527-330X
ISSN	1090-820X ; 1084-0761
DOI	10.1093/asj/sjw211
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Zs.A 5721: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 570: Show issues

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Article ; Online: The Nucleolar Protein Nucleophosmin Is Physiologically Secreted by Endothelial Cells in Response to Stress Exerting Proangiogenic Activity Both In Vitro and In Vivo

Anna Di Carlo / Sara Beji / Silvia Palmerio / Mario Picozza / Marco D’Agostino / Vincenzo Petrozza / Roberta Melchionna / Antonia Germani / Alessandra Magenta / Elena De Falco / Daniele Avitabile

International Journal of Molecular Sciences, Vol 22, Iss 3672, p

2021 Volume 3672

Abstract	Nucleophosmin (NPM), a nucleolar multifunctional phosphoprotein, acts as a stress sensor in different cell types. NPM can be actively secreted by inflammatory cells, however its biology on endothelium remains unexplored. In this study, we show for the first time that NPM is secreted by human vein endothelial cells (HUVEC) in the early response to serum deprivation and that NPM acts as a pro-inflammatory and angiogenic molecule both in vitro and in vivo. Accordingly, 24 h of serum starvation condition induced NPM relocalization from the nucleus to cytoplasm. Interestingly, NPM was increasingly excreted in HUVEC-derived conditioned media in a time dependent fashion upon stress conditions up to 24 h. The secretion of NPM was unrelated to cell necrosis within 24 h. The treatment with exogenous and recombinant NPM (rNPM) enhanced migration as well as the Intercellular Adhesion Molecule 1 (ICAM-1) but not Vascular cell adhesion protein 1 (VCAM-1) expression and it did not affect cell proliferation. Notably, in vitro tube formation by Matrigel assay was significantly increased in HUVEC treated with rNPM compared to controls. This result was confirmed by the in vivo injection of Matrigel plug assay upon stimulation with rNPM, displaying significant enhanced number of functional capillaries in the plugs. The stimulation with rNPM in HUVEC was also associated to the increased expression of master genes regulating angiogenesis and migration, including Vascular Endothelial Growth Factor-A ( VEGF-A ), Hepatocyte Growth Factor ( HGF ), Stromal derived factor-1 ( SDF-1 ), Fibroblast growth factor-2 ( FGF-2 ), Platelet Derived Growth Factor-B ( PDGF-B ), and Matrix metallopeptidase 9 ( MMP9 ). Our study demonstrates for the first time that NPM is physiologically secreted by somatic cells under stress condition and in the absence of cell necrosis. The analysis of the biological effects induced by NPM mainly related to a pro-angiogenic and inflammatory activity might suggest an important autocrine/paracrine role for NPM in the regulation of both phenomena.
Keywords	nucleophosmin ; HUVEC ; angiogenesis ; VEGF ; inflammation ; alarmin ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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