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      Bee Updated: Current Knowledge on Bee Venom and Bee Envenoming Therapy

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          Abstract

          Honey bees can be found all around the world and fulfill key pollination roles within their natural ecosystems, as well as in agriculture. Most species are typically docile, and most interactions between humans and bees are unproblematic, despite their ability to inject a complex venom into their victims as a defensive mechanism. Nevertheless, incidences of bee stings have been on the rise since the accidental release of Africanized bees to Brazil in 1956 and their subsequent spread across the Americas. These bee hybrids are more aggressive and are prone to attack, presenting a significant healthcare burden to the countries they have colonized. To date, treatment of such stings typically focuses on controlling potential allergic reactions, as no specific antivenoms against bee venom currently exist. Researchers have investigated the possibility of developing bee antivenoms, but this has been complicated by the very low immunogenicity of the key bee toxins, which fail to induce a strong antibody response in the immunized animals. However, with current cutting-edge technologies, such as phage display, alongside the rise of monoclonal antibody therapeutics, the development of a recombinant bee antivenom is achievable, and promising results towards this goal have been reported in recent years. Here, current knowledge on the venom biology of Africanized bees and current treatment options against bee envenoming are reviewed. Additionally, recent developments within next-generation bee antivenoms are presented and discussed.

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          Economic valuation of the vulnerability of world agriculture confronted with pollinator decline

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            Melittin: a membrane-active peptide with diverse functions.

            Melittin is the principal toxic component in the venom of the European honey bee Apis mellifera and is a cationic, hemolytic peptide. It is a small linear peptide composed of 26 amino acid residues in which the amino-terminal region is predominantly hydrophobic whereas the carboxy-terminal region is hydrophilic due to the presence of a stretch of positively charged amino acids. This amphiphilic property of melittin has resulted in melittin being used as a suitable model peptide for monitoring lipid-protein interactions in membranes. In this review, the solution and membrane properties of melittin are highlighted, with an emphasis on melittin-membrane interaction using biophysical approaches. The recent applications of melittin in various cellular processes are discussed.
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              The magic glue hyaluronan and its eraser hyaluronidase: a biological overview.

              Hyaluronan (HA) is a multifunctional high molecular weight polysaccharide found throughout the animal kingdom, especially in the extracellular matrix (ECM) of soft connective tissues. HA is thought to participate in many biological processes, and its level is markedly elevated during embryogenesis, cell migration, wound healing, malignant transformation, and tissue turnover. The enzymes that degrade HA, hyaluronidases (HAases) are expressed both in prokaryotes and eukaryotes. These enzymes are known to be involved in physiological and pathological processes ranging from fertilization to aging. Hyaluronidase-mediated degradation of HA increases the permeability of connective tissues and decreases the viscosity of body fluids and is also involved in bacterial pathogenesis, the spread of toxins and venoms, acrosomal reaction/ovum fertilization, and cancer progression. Furthermore, these enzymes may promote direct contact between pathogens and the host cell surfaces. Depolymerization of HA also adversely affects the role of ECM and impairs its activity as a reservoir of growth factors, cytokines and various enzymes involved in signal transduction. Inhibition of HA degradation therefore may be crucial in reducing disease progression and spread of venom/toxins and bacterial pathogens. Hyaluronidase inhibitors are potent, ubiquitous regulating agents that are involved in maintaining the balance between the anabolism and catabolism of HA. Hyaluronidase inhibitors could also serve as contraceptives and anti-tumor agents and possibly have antibacterial and anti-venom/toxin activities. Additionally, these molecules can be used as pharmacological tools to study the physiological and pathophysiological role of HA and hyaluronidases.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                06 September 2019
                2019
                : 10
                : 2090
                Affiliations
                [1] 1Medical School, Federal University of Roraima , Boa Vista, Brazil
                [2] 2Department of Biotechnology and Biomedicine, Technical University of Denmark , Lyngby, Denmark
                [3] 3Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo , Ribeirão Preto, Brazil
                [4] 4Department of Biotechnology and Biosafety, Eskişehir Osmangazi University , Eskişehir, Turkey
                [5] 5Department of Biochemistry and Immunology, Medical School of Ribeirão Preto, University of São Paulo , Ribeirão Preto, Brazil
                Author notes

                Edited by: Sandip D. Kamath, James Cook University, Australia

                Reviewed by: Wayne Robert Thomas, University of Western Australia, Australia; Sarita Patil, Massachusetts General Hospital and Harvard Medical School, United States

                *Correspondence: Manuela B. Pucca manu.pucca@ 123456ufrr.br
                Andreas H. Laustsen ahola@ 123456bio.dtu.dk

                This article was submitted to Vaccines and Molecular Therapeutics, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2019.02090
                6743376
                31552038
                19802b1d-5d63-4145-9803-ccad026bc8df
                Copyright © 2019 Pucca, Cerni, Oliveira, Jenkins, Argemí, Sørensen, Ahmadi, Barbosa and Laustsen.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 16 June 2019
                : 19 August 2019
                Page count
                Figures: 4, Tables: 1, Equations: 0, References: 194, Pages: 15, Words: 12517
                Categories
                Immunology
                Review

                Immunology
                bee antivenom,bee allergy,bee envenoming,bee therapy,bee toxins,bee venom
                Immunology
                bee antivenom, bee allergy, bee envenoming, bee therapy, bee toxins, bee venom

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