scholarly journals Natural Compounds as Target Biomolecules in Cellular Adhesion and Migration: From Biomolecular Stimulation to Label-Free Discovery and Bioactivity-Based Isolation

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1781
Author(s):  
Beatrix Péter ◽  
Imre Boldizsár ◽  
Gábor M. Kovács ◽  
Anna Erdei ◽  
Zsuzsa Bajtay ◽  
...  

Plants and fungi can be used for medical applications because of their accumulation of special bioactive metabolites. These substances might be beneficial to human health, exerting also anti-inflammatory and anticancer (antiproliferative) effects. We propose that they are mediated by influencing cellular adhesion and migration via various signaling pathways and by directly inactivating key cell adhesion surface receptor sites. The evidence for this proposition is reviewed (by summarizing the natural metabolites and their effects influencing cellular adhesion and migration), along with the classical measuring techniques used to gain such evidence. We systematize existing knowledge concerning the mechanisms of how natural metabolites affect adhesion and movement, and their role in gene expression as well. We conclude by highlighting the possibilities to screen natural compounds faster and more easily by applying new label-free methods, which also enable a far greater degree of quantification than the conventional methods used hitherto. We have systematically classified recent studies regarding the effects of natural compounds on cellular adhesion and movement, characterizing the active substances according to their organismal origin (plants, animals or fungi). Finally, we also summarize the results of recent studies and experiments on SARS-CoV-2 treatments by natural extracts affecting mainly the adhesion and entry of the virus.

2018 ◽  
Vol 9 (4) ◽  
pp. 74 ◽  
Author(s):  
Diana Sequeira ◽  
Catarina Seabra ◽  
Paulo Palma ◽  
Ana Cardoso ◽  
João Peça ◽  
...  

Background: The development of materials with bioregenerative properties is critically important for vital pulp therapies and regenerative endodontic procedures. The aim of this study was to evaluate the cytocompatibility and cytotoxicity of a new endodontic biomaterial, PulpGuard, in comparison with two other biomaterials widely used in endodontic procedures, ProRoot Mineral Trioxide Aggregate (MTA) and Biodentine. Methods: Apical papilla cells (APCs) were isolated from third molars with incomplete rhizogenesis from patients with orthodontic indication for dental extraction. Cultured APCs were incubated for 24, 48, or 72 h with different dilutions of eluates prepared from the three materials. Cellular viability, mobility, and proliferation were assessed in vitro using the Alamar Blue assay and a wound-healing test. The cells were also cultured in direct contact with the surface of each material. These were then analyzed via Scanning Electron Microscopy (SEM), and the surface chemical composition was determined by Energy-Dispersive Spectroscopy (EDS). Results: Cells incubated in the presence of eluates extracted from ProRoot MTA and PulpGuard presented rates of viability comparable to those of control cells; in contrast, undiluted Biodentine eluates induced a significant reduction of cellular viability. The wound-healing assay revealed that eluates from ProRoot MTA and PulpGuard allowed for unhindered cellular migration and proliferation. Cellular adhesion was observed on the surface of all materials tested. Consistent with their disclosed composition, EDS analysis found high relative abundance of calcium in Biodentine and ProRoot MTA and high abundance of silicon in PulpGuard. Significant amounts of zinc and calcium were also present in PulpGuard discs. Concerning solubility, Biodentine and ProRoot MTA presented mild weight loss after eluate extraction, while PulpGuard discs showed significant water uptake. Conclusions: PulpGuard displayed a good in vitro cytocompatibility profile and did not significantly affect the proliferation and migration rates of APCs. Cells cultured in the presence of PulpGuard eluates displayed a similar profile to those cultured with eluates from the widely used endodontic cement ProRoot MTA.


2010 ◽  
Vol 190 (4) ◽  
pp. 675-691 ◽  
Author(s):  
Mark T. Howes ◽  
Matthew Kirkham ◽  
James Riches ◽  
Katia Cortese ◽  
Piers J. Walser ◽  
...  

Although the importance of clathrin- and caveolin-independent endocytic pathways has recently emerged, key aspects of these routes remain unknown. Using quantitative ultrastructural approaches, we show that clathrin-independent carriers (CLICs) account for approximately three times the volume internalized by the clathrin-mediated endocytic pathway, forming the major pathway involved in uptake of fluid and bulk membrane in fibroblasts. Electron tomographic analysis of the 3D morphology of the earliest carriers shows that they are multidomain organelles that form a complex sorting station as they mature. Proteomic analysis provides direct links between CLICs, cellular adhesion turnover, and migration. Consistent with this, CLIC-mediated endocytosis of key cargo proteins, CD44 and Thy-1, is polarized at the leading edge of migrating fibroblasts, while transient ablation of CLICs impairs their ability to migrate. These studies provide the first quantitative ultrastructural analysis and molecular characterization of the major endocytic pathway in fibroblasts, a pathway that provides rapid membrane turnover at the leading edge of migrating cells.


2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Claudia Cerella ◽  
Flavia Radogna ◽  
Mario Dicato ◽  
Marc Diederich

Even though altered metabolism is an “old” physiological mechanism, only recently its targeting became a therapeutically interesting strategy and by now it is considered an emerging hallmark of cancer. Nevertheless, a very poor number of compounds are under investigation as potential modulators of cell metabolism. Candidate agents should display selectivity of action towards cancer cells without side effects. This ideal favorable profile would perfectly overlap the requisites of new anticancer therapies and chemopreventive strategies as well. Nature represents a still largely unexplored source of bioactive molecules with a therapeutic potential. Many of these compounds have already been characterized for their multiple anticancer activities. Many of them are absorbed with the diet and therefore possess a known profile in terms of tolerability and bioavailability compared to newly synthetized chemical compounds. The discovery of important cross-talks between mediators of the most therapeutically targeted aberrancies in cancer (i.e., cell proliferation, survival, and migration) and the metabolic machinery allows to predict the possibility that many anticancer activities ascribed to a number of natural compounds may be due, in part, to their ability of modulating metabolic pathways. In this review, we attempt an overview of what is currently known about the potential of natural compounds as modulators of cancer cell metabolism.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2889-2889 ◽  
Author(s):  
Neeta Shirvaikar ◽  
Jencet Montano ◽  
Andrew R. Turner ◽  
Mariusz Z. Ratajczak ◽  
Anna Janowska-Wieczorek

Abstract Hyaluronic acid (HA), the bone marrow (BM) extracellular matrix microenvironment (ECM) component, not only supports cell adhesion but also promotes migration and homing of hematopoietic stem/progenitor cells (HSPC) by interacting with its cell surface receptor CD44. CD44 has been shown to co-localize with matrix metalloproteinases (MMPs), particularly membrane-type (MT)-1 MMP and MMP-9, at the leading edge of migrating tumor cells, and the cleavage of CD44 by MT1-MMP is critical for tumor cell migration and invasion. MT1-MMP has strong pericellular proteolytic activity and also activates latent forms of MMP-2 and MMP-9. In this study we examined the effect of HA on MT1-MMP expression and migration of BM, peripheral blood and cord blood CD34+ cells. We found that HA upregulates mRNA for MT1-MMP and MMP-9, increases MT1-MMP protein (as evaluated by Western blotting) and stimulates MMP-9 and MMP-2 activity (as determined by zymography) in CD34+ cells. In chemotaxis assays HA alone did not show any chemotactic activity but primed the chemotaxis of CD34+ cells to a low SDF-1 gradient (10 ng/mL) and their trans-Matrigel chemoinvasion to a low SDF-1 gradient. Similarly, SDF-1 besides stimulating MMP-2 and MMP-9 (as we previously described in Exp Hematol2000; 28:1274), also upregulated MT1-MMP in CD34+ cells. In addition, we found that the HA enhanced activation of latent MMP-2 in co-cultures of CD34+ cells with HUVEC. In conclusion, we demonstrate for the first time that (i) HA primes CD34+ cell chemotaxis and chemoinvasion to a low SDF-1 gradient; (ii) that both HA and SDF-1 stimulate MT1-MMP, MMP-2 and MMP-9 in CD34+ cells, and (iii) HA enhances activation of proMMP-2 in the ECM. Hence the interaction of HA and SDF-1 with MT1-MMP could play an important role in HSPC migration and homing and we postulate that pretreatment of HSPC with HA before transplantation could enhance their homing by inducing expression of MMPs that is optimal for stem cell engraftment.


Author(s):  
Amrinder S. Nain ◽  
Eric Miller ◽  
Metin Sitti ◽  
Phil Campbell ◽  
Cristina Amon

For regenerative medicine applications, we need to expand our understanding of the mechanisms by which nature assembles and functionalizes specialized complex tissues to form a complete organism. The first step towards this goal involves understanding the underlying complex mechanisms of highly organized behavior spanning not only diverse scientific fields, but also nano, micro and macro length-scales. For example, an engineered fibrous biomaterial scaffold possessing the hierarchal spatial properties of a native extracellular matrix (ECM) can serve as a building block upon which living cells are seeded for repair or regeneration. The hierarchical nature of ECM along with the inherent topological constraints of fiber diameter, fiber spacing, multi-layer configurations provide different pathways for living cells to adapt and conform to the surrounding environment. Our previously developed Spinneret based Tunable Engineered Parameters (STEP) technique to deposit biomaterial scaffolds in aligned configurations has been used for the first time to deposit single and multi-layer biological scaffolds of fibrinogen. Fibrinogen is a very well established tissue engineering scaffold material, as it improves cellular interactions and allows scaffold remodeling compared to synthetic polymers. Current state-of-the-art fiber deposition techniques lack the ability to fabricate scaffolds of desired fiber dimensions and orientations and in this study we present fabrication and aligned deposition of fibrinogen fiber arrays with diameters ranging from sub-200 nm to sub-microns and several millimeters in length. The fabricated scaffolds are then cultured with pluripotent mouse C2C12 cells for seven days and cells on the scaffolds are observed to elongate resembling myotube morphology along the fiber axis, spread along intersecting layers and fuse into bundles at the macroscale. Additionally, we demonstrate the ability to deposit poly (lactic-co-glycolic acid) (PLGA), Polystyrene (PS) biomaterial scaffolds of different diameters to investigate the effects of topological variations on cellular adhesion, proliferation and migration. Previous studies have indicated cells making right angle transitions upon encountering perpendicular double layer fibers and cellular motion is thwarted in the vicinity of diverging fibers. Current ongoing studies are aimed at determining the effects of fiber diameter and fiber spacing on mouse C2C12 cellular adhesion and migration, which are envisioned to aid in the design of future scaffolds for tissue engineering possessing appropriate material and geometrical properties.


2012 ◽  
Vol 6 (2) ◽  
pp. 78-84 ◽  
Author(s):  
Georgina N. Montagna ◽  
Kai Matuschewski ◽  
Carlos A. Buscaglia

2021 ◽  
Author(s):  
Eden Ross

The cell-surface proteome controls numerous cellular functions and is dynamically controlled by endocytosis and recycling under different cellular conditions. Energy stress is a state in which a cell must engage adaptive responses to ensure survival, including remodelling of the cell-surface proteome. AMP-activated protein kinase (AMPK) is an important metabolic regulator in the cell. Recent studies suggest AMPK activation may alter the endocytosis of a few specific proteins. How increased AMPK activity globally regulates the cell surface proteome is not known. I have developed a method to isolate the cell surface proteome from cultured cells. Coupling this method to quantitative mass spectrometry has allowed systematic identification of changes in the cell-surface proteome upon metabolic regulation. I found that activation of AMPK results in robust changes in the cell surface proteome, including cell adhesion and migration proteins. I confirmed that AMPK activation elicits a decrease in the cell surface abundance of the adhesion and migration protein β1-integrin, and that this is correlated with altered function of the endocytosis protein Dab2. Thus, my research furthers our understanding of how AMPK regulates the cell surface proteome and the specific mechanism by which AMPK regulates cellular adhesion and migration.


Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1095
Author(s):  
Stefania Lamponi

Natural anticoagulant drugs can be obtained from plants, rich in secondary bioactive metabolites which, in addition to being effective antioxidants, also possess anticoagulant and antiplatelet properties and, for this reason, can be excellent candidates for the treatment of thrombotic diseases. This review reports an overview of the hemostatic process and thrombotic disorders together with data on plants, more and less common from around the world, containing bioactive compounds characterized by antiplatelet and anticoagulant activity. The reported literature was obtained from Medline, PubMed, Elsevier, Web of Science, Google Scholar considering only articles in the English language, published in peer-reviewed journals. The number of citations of the articles and the impact factor of the journals were other parameters used to select the scientific papers to be included in the review. The analysis of the literature data selected demonstrates that many plants’ bioactive compounds show antiplatelet and anticoagulant activity that make them potential candidates to be used as new natural compounds able to interfere with both primary and secondary hemostasis. Moreover, they could be used together with anticoagulants currently administered in clinical practice to increase their efficacy and to reduce complications in the treatment of thrombotic disorders.


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