1,720,963 research outputs found
Mesoglycan connects Syndecan-4 and VEGFR2 through Annexin A1 and formyl peptide receptors to promote angiogenesis in vitro
No full textMesoglycan is a mixture of glycosaminoglycans (GAG) with fibrinolytic effects and the potential to enhance skin wound repair. Here, we have used endothelial cells isolated from wild-type (WT) and Syndecan-4 null (Sdc4-/-) C57BL/6 mice to demonstrate that mesoglycan promotes cell motility and in vitro angiogenesis acting on the co-receptor Syndecan-4 (SDC4). This latter is known to participate in the formation and release of extracellular vesicles (EVs). We characterized EVs released by HUVECs and assessed their effect on angiogenesis. Particularly, we focused on Annexin A1 (ANXA1) containing EVs, since they may contribute to tube formation via interactions with Formyl peptide receptors (FPRs). In our model, the bond ANXA1-FPRs stimulates the release of vascular endothelial growth factor (VEGF-A) that interacts with vascular endothelial receptor-2 (VEGFR2) and activates the pathway enhancing cell motility in an autocrine manner, as shown by wound healing/invasion assays, and the induction of endothelial to mesenchymal transition (EndMT). Thus, we have shown for the first time that mesoglycan exerts its pro-angiogenic effects in the healing process triggering the activation of the three interconnected molecular axis: mesoglycan-SDC4, EVs-ANXA1-FPRs, and VEGF-A-VEGFR2
The pyrazolyl-urea gege3 inhibits the activity of ANXA1 in the angiogenesis induced by the pancreatic cancer derived EVs
No full textThe pyrazolyl-urea Gege3 molecule has shown interesting antiangiogenic effects in the tumor contest. Here, we have studied the role of this compound as interfering with endothelial cells activation in response to the paracrine effects of annexin A1 (ANXA1), known to be involved in promoting tumor progression. ANXA1 has been analyzed in the extracellular environment once secreted through microvesicles (EVs) by pancreatic cancer (PC) cells. Particularly, Gege3 has been able to notably prevent the effects of Ac2-26, the ANXA1 mimetic peptide, and of PC-derived EVs on endothelial cells motility, angiogenesis, and calcium release. Furthermore, this compound also inhibited the translocation of ANXA1 to the plasma membrane, otherwise induced by the same ANXA1-dependent extracellular stimuli. Moreover, these effects have been mediated by the indirect inhibition of protein kinase Cα (PKCα), which generally promotes the phosphorylation of ANXA1 on serine 27. Indeed, by the subtraction of intracellular calcium levels, the pathway triggered by PKCα underwent a strong inhibition leading to the following impediment to the ANXA1 localization at the plasma membrane, as revealed by confocal and cytofluorimetry analysis. Thus, Gege3 appeared an attractive molecule able to prevent the paracrine effects of PC cells deriving ANXA1 in the tumor microenvironment
Annexin A1 Is Involved in the Antitumor Effects of 5-Azacytidine in Human Oral Squamous Carcinoma Cells
No full text: Background: the treatment of squamous cell carcinomas of the oral cavity (OSCCs) is limited by the lack of reliable diagnostic/prognostic, and predictive markers, as well as by intrinsic tumor cell heterogeneity. 5-azacytidine (5-AZA) offers opportunities for cancer cell reprogramming to develop new target-specific treatments. The protein annexin A1 (ANXA1) is downregulated in head and neck squamous cell carcinoma (HNSCC), correlated with pathological differentiation grade. Objectives: this work aimed to further investigate the role of ANXA1 in OSCC progression based on 5-AZA activity. Methods: we used CAL27 and CAL33 cell lines, which differ in drug sensitivity and differentiation status. Results: CAL27 showed a higher expression of the stemness markers compared to CAL33 cells, but this positivity was lost after treatment with 5-AZA. This drug also decreased CAL27 cell motility, promoting a less aggressive phenotype. Moreover, 5-AZA increased ANXA1 expression only in CAL27. After siRNA-mediated downmodulation, we witnessed a significant rise in cell motility and the inversion of E-/N-cadherin expression, which was reverted again by 5-AZA. To investigate the role of exogenous ANXA1 derived from the tumor microenvironment, we treated CAL27 with Ac2-26, an ANXA1 mimetic peptide. Interestingly, we found that this peptide alone showed impacts similar to 5-AZA in reversing the aggressive phenotype. All these effects were not evidenced in CAL33 cells. Finally, to prove the loop of the exogenous protein, we detected increased expression of its receptors, formyl peptide receptors (FPRs), and their activation, leading to oncosuppressor effects. Conclusions: we propose that ANXA1 mediates the effects of 5-AZA only in poorly differentiated stemlike CAL27 cell lines. This suggests the relevance of ANXA1 as a diagnostic/prognostic biomarker in OSCCs, paving the way for personalized therapies to overcome treatment difficulties
Anxa1 contained in evs regulates macrophage polarization in tumor microenvironment and promotes pancreatic cancer progression and metastasis
No full textThe tumor microenvironment (TME) is a dynamic system where nontumor and cancer cells intercommunicate through soluble factors and extracellular vesicles (EVs). The TME in pancreatic cancer (PC) is critical for its aggressiveness and the annexin A1 (ANXA1) has been identified as one of the oncogenic elements. Previously, we demonstrated that the autocrine/paracrine activities of extracellular ANXA1 depend on its presence in EVs. Here, we show that the complex ANXA1/EVs modulates the macrophage polarization further contributing to cancer progression. The EVs isolated from wild type (WT) and ANXA1 knock-out MIA PaCa-2 cells have been administrated to THP-1 macrophages finding that ANXA1 is crucial for the acquisition of a protumor M2 phenotype. The M2 macrophages activate endothelial cells and fibroblasts to induce angiogenesis and matrix degradation, respectively. We have also found a significantly increased presence of M2 macrophage in mice tumor and liver metastasis sections previously obtained by orthotopic xenografts with WT cells. Taken together, our data interestingly suggest the relevance of ANXA1 as potential diagnostic/prognostic and/or therapeutic PC marker
The promising pro-healing role of the association of mesoglycan and lactoferrin on skin lesions
No full textSkin wound repair represents an important topic for the therapeutic challenges. Many molecules are commonly used as active principles of topical devices to induce the correct tissue regeneration. Among these molecules, mesoglycan, a mixture of glycosaminoglycans, and the lactoferrin have recently aroused interest. Here, for the first time, we used mesoglycan/lactoferrin to treat the cell populations mainly involved in wound healing. We showed that human keratinocytes, fibroblasts and endothelial cells migrate and invade more rapidly when treated with the association. Moreover, we found that mesoglycan/lactoferrin, are able to trigger the differentiation process of keratinocytes, the switch of the fibroblasts into myofibroblasts, the acquisition of a mesenchymal phenotype for the endothelial cells which, in this way, start to form the capillary-like structures. Additionally, we proved that the well known antimicrobial behavior of lactoferrin encourages the inhibition of S. aureus and P. aeruginosa biofilm formation by the whole association, providing an appealing feature for this formulation. Finally, by the in vivo analysis, we showed that the mesoglycan/lactoferrin favors the closure of skin wounds performed on the mice back. Beside the decrease of the lesion diameters, by a confocal analysis of mice biopsies we found that the use of the association strongly promote cell activation underlying the correct tissue regeneration. These results encourage to further investigation aiming the development of a new topical patch that includes this association
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
The procoagulant activity of emoxilane®: A new appealing therapeutic use in epistaxis of the combination of sodium hyaluronate, silver salt, α-tocopherol and d-panthenol
No full textEpistaxis is one of the most frequent hemorrhages resulting from local or systemic factors. Its management without hospitalization has prompted an interest in locally applied hemostatic agents. Generally, the therapy approaches involve sprays or creams acting as a physical barrier, even used as tampons or gauze. In this study, we have investigated the activity of Emoxilane®, a combination of sodium hyaluronate, silver salt, α-tocopherol acetate and D-panthenol, which is known to be able to separately act in a different biological manner. Our in vitro results, obtained on endothelial and nasal epithelial cells, have shown that the association of these molecules presented a notable antioxidant activity mainly due to the α-tocopherol and D-panthenol and a significant antimicrobial role thanks to the silver compound. Moreover, remarkable hemostatic activity was found by evaluating plasmin inhibition attributable to the sodium hyaluronate. Interestingly, on human plasma, we have confirmed that Emoxilane® strongly induced the increase of thrombin levels. These data suggest that the use of this association could represent an appealing pharmacological approach to actively induce hemostasis during epistaxis. Our future perspective will aim to the creation of a formulation for an easy topical application in the nose which is able to contrast the bleeding
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