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https://www.readbyqxmd.com/read/29145017/membrane-interactions-of-microgels-as-carriers-of-antimicrobial-peptides
#1
Randi Nordström, Lina Nyström, Oliver C J Andrén, Michael Malkoch, Anita Umerska, Mina Davoudi, Artur Schmidtchen, Martin Malmsten
Microgels are interesting as potential delivery systems for antimicrobial peptides. In order to elucidate membrane interactions of such systems, we here investigate effects of microgel charge density on antimicrobial peptide loading and release, as well as consequences of this for membrane interactions and antimicrobial effects, using ellipsometry, circular dichroism spectroscopy, nanoparticle tracking analysis, dynamic light scattering and z-potential measurements. Anionic poly(ethyl acrylate-co-methacrylic acid) microgels were found to incorporate considerable amounts of the cationic antimicrobial peptides LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES) and DPK-060 (GKHKNKGKKNGKHNGWKWWW) and to protect incorporated peptides from degradation by infection-related proteases at high microgel charge density...
November 6, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/29142299/the-immunomodulatory-drug-glatiramer-acetate-is-also-an-effective-antimicrobial-agent-that-kills-gram-negative-bacteria
#2
Stig Hill Christiansen, Ronan A Murphy, Kristian Juul-Madsen, Marlene Fredborg, Michael Lykke Hvam, Esben Axelgaard, Sandra M Skovdal, Rikke Louise Meyer, Uffe B Skov Sørensen, Arne Möller, Jens Randel Nyengaard, Niels Nørskov-Lauritsen, Mikala Wang, Mihaela Gadjeva, Kenneth A Howard, Jane C Davies, Eskild Petersen, Thomas Vorup-Jensen
Classic drug development strategies have failed to meet the urgent clinical needs in treating infections with Gram-negative bacteria. Repurposing drugs can lead to timely availability of new antibiotics, accelerated by existing safety profiles. Glatiramer acetate (GA) is a widely used and safe formulation for treatment of multiple sclerosis. It contains a large diversity of essentially isomeric polypeptides with the cationic and amphiphilic character of many antimicrobial peptides (AMP). Here, we report that GA is antibacterial, targeting Gram-negative organisms with higher activity towards Pseudomonas aeruginosa than the naturally-occurring AMP LL-37 in human plasma...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133814/structural-remodeling-and-oligomerization-of-human-cathelicidin-on-membranes-suggest-fibril-like-structures-as-active-species
#3
Enea Sancho-Vaello, Patrice François, Eve-Julie Bonetti, Hauke Lilie, Sebastian Finger, Fernando Gil-Ortiz, David Gil-Carton, Kornelius Zeth
Antimicrobial peptides as part of the mammalian innate immune system target and remove major bacterial pathogens, often through irreversible damage of their cellular membranes. To explore the mechanism by which the important cathelicidin peptide LL-37 of the human innate immune system interacts with membranes, we performed biochemical, biophysical and structural studies. The crystal structure of LL-37 displays dimers of anti-parallel helices and the formation of amphipathic surfaces. Peptide-detergent interactions introduce remodeling of this structure after occupation of defined hydrophobic sites at the dimer interface...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29099325/functional-expression-purification-and-antimicrobial-activity-of-a-novel-antimicrobial-peptide-mlh-in-escherichia-coli
#4
Guo-Li Gong, Yuan Wei, Zhong-Zhong Wang
In this study, a novel heterozygous antimicrobial peptide MLH was synthesized, expressed, purified and characterized. The peptide MLH was selected through bioinformatic analysis using musca domestica antimicrobial peptide (Cec-Med), human antimicrobial peptide LL-37 and helicobacter pylori antimicrobial peptide (Hp) as parent peptides. The target gene was synthesized by overlap extension PCR (SOE-PCR) and connected to the expression vector pET-32a (+), and the recombinant plasmid pET-32a-MLH was transformed to Escherichia coli for constructing pET-32a-MLH/BL21 (DE3)...
November 3, 2017: Preparative Biochemistry & Biotechnology
https://www.readbyqxmd.com/read/29091929/the-cathelicidin-protein-cramp-is-a-potential-atherosclerosis-self-antigen-in-apoe-mice
#5
Peter M Mihailovic, Wai Man Lio, Juliana Yano, Xiaoning Zhao, Jianchang Zhou, Kuang-Yuh Chyu, Prediman K Shah, Bojan Cercek, Paul C Dimayuga
Auto-immunity is believed to contribute to inflammation in atherosclerosis. The antimicrobial peptide LL-37, a fragment of the cathelicidin protein precursor hCAP18, was previously identified as an autoantigen in psoriasis. Given the reported link between psoriasis and coronary artery disease, the biological relevance of the autoantigen to atherosclerosis was tested in vitro using a truncated (t) form of the mouse homolog of hCAP18, CRAMP, on splenocytes from athero-prone ApoE(-/-) mice. Stimulation with tCRAMP resulted in increased CD8+ T cells with Central Memory and Effector Memory phenotypes in ApoE(-/-) mice, differentially activated by feeding with normal chow or high fat diet...
2017: PloS One
https://www.readbyqxmd.com/read/29091380/real-world-efficacy-of-azelaic-acid-15-gel-for-the-reduction-of-inflammatory-lesions-of-rosacea
#6
P J Wirth, M H Henderson Berg, N Sadick
Approximately 16 million Americans have rosacea, an inflammatory cutaneous disorder with central facial erythema, papules, pustules, telangiectasia, flushing, and swelling being among the more commonly recognized features. Overexpression of cathelicidin peptide LL-37 has been implicated in the pathophysiology of rosacea. Azelaic acid has been found to inhibit the pathologic expression of cathelicidin, as well as the hyperactive protease activity that cleaves cathelicidin into LL-37. Given these findings, a small prospective, open-label, interventional trial was undertaken to assess the effects of azelaic acid 15% gel on inflammatory lesions of papulopustular rosacea in a real-world setting...
November 2017: Skin Therapy Letter
https://www.readbyqxmd.com/read/29077044/inhibition-of-human-kallikrein-5-protease-by-triterpenoids-from-natural-sources
#7
Yosuke Matsubara, Takashi Matsumoto, Junichi Koseki, Atsushi Kaneko, Setsuya Aiba, Kenshi Yamasaki
Stratum corneum tryptic enzyme kallikrein 5 (KLK5) is a serine protease that is involved in the cell renewal and maintenance of the skin barrier function. The excessive activation of KLK5 causes an exacerbation of dermatoses, such as rosacea and atopic dermatitis. Some triterpenoids are reported to suppress the serine proteases. We aimed to investigate whether bioactive triterpenoids modulate the KLK5 protease. Nineteen triterpenoids occurring in medicinal crude drugs were evaluated using an enzymatic assay to measure the anti-KLK5 activity...
October 27, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29065709/direct-effects-of-fermented-cow-s-milk-product-with-lactobacillus-paracasei-cba-l74-on-human-enterocytes
#8
L Paparo, R Aitoro, R Nocerino, C Fierro, C Bruno, R Berni Canani
Cow's milk fermented with Lactobacillus paracasei CBA L74 (FM-CBAL74) exerts a preventive effect against infectious diseases in children. We evaluated if this effect is at least in part related to a direct modulation of non-immune and immune defence mechanisms in human enterocytes. Human enterocytes (Caco-2) were stimulated for 48 h with FM-CBAL74 at different concentrations. Cell growth was assessed by colorimetric assay; cell differentiation (assessed by lactase expression), tight junction proteins (zonula occludens1 and occludin), mucin 2, and toll-like receptor (TRL) pathways were analysed by real-time PCR; innate immunity peptide synthesis, beta-defensin-2 (HBD-2) and cathelicidin (LL-37) were evaluated by ELISA...
October 25, 2017: Beneficial Microbes
https://www.readbyqxmd.com/read/29034266/bladder-pain-in-an-ll-37-interstitial-cystitis-and-painful-bladder-syndrome-model
#9
Wanjian Jia, Austin J Schults, Mark Martin Jensen, Xiangyang Ye, Jeremiah A Alt, Glenn D Prestwich, Siam Oottamasathien
Our goal was to evaluate the pain response in an LL-37 induced murine model for interstitial cystitis/painful bladder syndrome (IC/PBS). In particular, we sought to characterize the dose dependence, time-course, and relationship of LL-37 induced bladder inflammation and pain. The IC/PBS model was induced in C57Bl/6 mice by instilling 50 μL of LL-37, an immunomodulatory human cathelicidin (anti-microbial peptide), in the bladder for 1 hr. Pain responses were measured using von Frey filaments (0.04 gm to 4.0 gm) before and after LL-37 instillation...
2017: American Journal of Clinical and Experimental Urology
https://www.readbyqxmd.com/read/29034104/fibroblasts-the-unknown-sentinels-eliciting-immune-responses-against-microorganisms
#10
REVIEW
Luis Antonio Bautista-Hernández, José Luis Gómez-Olivares, Beatriz Buentello-Volante, Victor Manuel Bautista-de Lucio
Fibroblasts are present in all tissues but predominantly in connective tissues. Some of their functions include contractility, locomotion, collagen and elastin fiber production, and the regulation and degradation of the extracellular matrix. Also, fibroblasts act as sentinels to produce inflammatory mediators in response to several microorganisms. There is evidence that fibroblasts can synthesize toll-like receptors (TLRs), antimicrobial peptides, proinflammatory cytokines, chemokines, and growth factors, which are important molecules involved in innate immune response against microorganisms...
September 2017: European Journal of Microbiology & Immunology
https://www.readbyqxmd.com/read/29033090/the-antimicrobial-peptide-ll-37-as-a-possible-adjunct-for-the-proliferation-and-differentiation-of-dental-pulp-stem-cells
#11
Noala Vicensoto Moreira Milhan, Patricia Pimentel de Barros, Elis Andrade de Lima Zutin, Felipe Eduardo de Oliveira, Carlos Henrique Ribeiro Camargo, Samira Esteves Afonso Camargo
INTRODUCTION: This study evaluated the biocompatibility of 5 and 10 μg/mL LL-37 in vitro and its effect on the differentiation of human dental pulp stem cells (DPSCs) into odontoblast-like cells. METHODS: Cell viability, genotoxicity, nitric oxide production, cell cycle, dentine sialophosphoprotein (DSPP) production, and DSPP gene expression. RESULTS: Concentrations of 5 and 10 μg/mL of LL-37 were not cytotoxic and generally increased cell viability, especially on the third day (P < ...
October 12, 2017: Journal of Endodontics
https://www.readbyqxmd.com/read/29022391/kr-12-a5-is-a-non-cytotoxic-agent-with-potent-antimicrobial-effects-against-oral-pathogens
#12
Karina Sampaio Caiaffa, Loiane Massunari, Marcelle Danelon, Gabriel Flores Abuna, Telma Blanca Lombardo Bedran, Norival Alves Santos-Filho, Denise Madalena Palomari Spolidorio, Natalia Leal Vizoto, Eduardo Maffud Cilli, Cristiane Duque
This study evaluated the cytotoxicity and antimicrobial activity of analogs of cationic peptides against microorganisms associated with endodontic infections. L-929 fibroblasts were exposed to LL-37, KR-12-a5 and hBD-3-1C(V) and chlorhexidine (CHX, control), and cell metabolism was evaluated with MTT. The minimal inhibitory concentration (MIC) and the minimal bactericidal/fungicidal concentration (MBC/MFC) of the peptides and CHX were determined against oral pathogens associated with endodontic infections. Enterococcus faecalis and Streptococcus mutans biofilms were cultivated in bovine dentin blocks, exposed to different concentrations of the most efficient antimicrobial peptide and analyzed by confocal laser scanning microscopy...
October 12, 2017: Biofouling
https://www.readbyqxmd.com/read/28987032/functionalized-pva-silk-blended-nanofibrous-mats-promote-diabetic-wound-healing-via-regulation-of-extracellular-matrix-and-tissue-remodeling
#13
Dimple Chouhan, G Janani, Bijayashree Chakraborty, Samit K Nandi, Biman B Mandal
Chronic cutaneous ulcers, a complex pathophysiological diabetic condition, represent a critical clinical challenge in the current diabetes mellitus pandemic. Consequently, there is a compelling need for bioactive dressings which can trigger healing processes for complete wound repair. Silk fibroin (SF), a natural protein polymer from mulberry and non-mulberry silkworms, has properties that support accelerated wound healing rate. SF from non-mulberry variety possesses additional cell-binding motifs (RGD), offering cell-material interactions...
October 7, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28959904/body-composition-does-not-affect-serum-levels-of-cathelicidin-ll-37-in-elderly-women-with-unipolar-depression
#14
Ewa Szczepocka, Elżbieta Kozłowska, Ewa Brzezińska-Błaszczyk, Adam Wysokiński
OBJECTIVES: Antimicrobial peptides are components of the innate immune system. Cathelicidin LL-37 plays an important role in antimicrobial defense, exerts proinflammatory effect and strongly affects the immune system functioning. Our recent study revealed that serum concentration of LL-37 is increased in elderly women with depression. The aim of this study is to evaluate serum LL-37 levels in elderly women with depression and to compare them with non-depressed elderly women, matched for anthropometric and body composition parameters...
September 29, 2017: Nordic Journal of Psychiatry
https://www.readbyqxmd.com/read/28956425/serum-level-of-cathelicidin-ll-37-in-patients-with-active-tuberculosis-and-other-infectious-diseases
#15
K Majewski, J Agier, E Kozłowska, E Brzezińska-Błaszczyk
A growing body of evidence indicates the role of cathelicidin LL-37, a member of the antimicrobial peptide family, in host innate defense mechanisms. The important role of this peptide in infectious diseases is also suggested, however, to date, data relating to LL-37 expression in the course of bacterial infections are far from complete. Therefore, the aim of the present study was to determine LL-37 serum levels in adult patients with pulmonary tuberculosis (TB). For comparison, circulating LL-37 levels in patients with pneumonia induced by Gram-positive or Gram-negative bacteria species and in healthy subjects were evaluated...
July 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28955581/levels-of-ll-37-antimicrobial-peptide-in-the-gingival-crevicular-fluid-of-young-and-middle-aged-subjects-with-or-without-gingivitis
#16
Oya Turkoglu, Gulnur Emingul, Gulnihal Eren, Harika Atmaca, Necil Kutukculer, Gul Atilla
PURPOSE: LL-37 is an antimicrobial peptide which plays an important role in the innate immunity. The aim of this study was to investigate the LL-37 levels in the gingival crevicular fluid (GCF) of middle-aged and young adults who have either gingivitis or healthy periodontal tissues. MATERIALS AND METHODS: Forty middle-aged adults (20 healthy controls and 20 with gingivitis) and 41 younger adults (20 healthy controls and 21 with gingivitis) were included in the present study...
2017: J Istanb Univ Fac Dent
https://www.readbyqxmd.com/read/28950944/emerging-roles-for-mas-related-g-protein-coupled-receptor-x2-in-host-defense-peptide-opioid-and-neuropeptide-mediated-inflammatory-reactions
#17
Hydar Ali
Mast cells (MCs) are tissue-resident immune cells that contribute to host defense but are best known for their roles in allergic and inflammatory diseases. In humans, MCs are divided into two subtypes based on the protease content of their secretory granules. Thus, human lung MCs contain only tryptase and are known as MCT, whereas skin MCs contain both tryptase and chymase and are known as MCTC. Patients with severe asthma display elevated MCs in the lung, which undergo phenotypic change from MCT to MCTC. Although the human genome contains four Mas related G protein coupled receptor X (MRGPRX) genes, an important feature of MCTC is that they selectively express MRGPRX2...
2017: Advances in Immunology
https://www.readbyqxmd.com/read/28919413/apolipoprotein-a-i-attenuates-ll-37-induced-endothelial-cell-cytotoxicity
#18
Daniel Svensson, Jens O Lagerstedt, Bengt-Olof Nilsson, Rita Del Giudice
The human cathelicidin peptide LL-37 has antimicrobial and anti-biofilm functions, but LL-37 may also damage the host by triggering inflammation and exerting a cytotoxic effect, thereby reducing host cell viability. Human plasma mitigates LL-37-induced host cell cytotoxicity but the underlying mechanisms are not completely understood. Apolipoprotein A-I (ApoA-I) is a plasma protein endowed with atheroprotective effects. Here, we investigate the interaction between ApoA-I and LL-37 by biochemical techniques, and furthermore assess if ApoA-I protects against LL-37-evoked cytotoxicity in human umbilical vein endothelial cells (HUVEC)...
November 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28910167/expression-of-antimicrobial-peptides-by-uveal-and-cutaneous-melanoma-cells-and-investigation-of-their-role-in-tumor-cell-migration-and-vasculogenic-mimicry
#19
Joseph C Manarang, Deborah C Otteson, Alison M McDermott
AIMS: Antimicrobial peptides (AMPs) have been implicated in the pathogenesis of several cancers, although there is also evidence suggesting potential for novel, AMP-based antitumor therapies. Discerning potential roles of AMPs in tumor pathogenesis may provide valuable insight into the mechanisms of novel AMP-based antitumor therapy. METHODS: mRNA expression of the AMPs α defensin (HNP-1); cathelicidin (LL-37); and β defensins (hBD-1, hBD-2, hBD-3, hBD-4) in human uveal and cutaneous melanoma cell lines, primary human uveal melanocytes, and primary human uveal melanoma cells was determined by reverse transcriptase polymerase chain reaction...
November 2017: Current Eye Research
https://www.readbyqxmd.com/read/28890511/the-antibacterial-effects-of-antimicrobial-peptides-op-145-against-clinically-isolated-multi-resistant-strains
#20
Liu Ming, Jian-An Huang
OP-145 is a synthetic antimicrobial peptide developed from the human cathelicidin LL-37. The purpose of this investigation was to evaluate the effect of the antimicrobial peptide OP-145 against clinically isolated drug resistant strains. Ten Methicillin-resistant Staphylococcus aureus (MRSA) strains were obtained from our hospital's clinical inspection center and the activity of OP-145 on growth and biofilm formation on these strains was evaluated by colony counts and scanning electron microscopy. The antimicrobial peptide OP-145 showed significant antibacterial activity against 9 MRSA strains...
September 11, 2017: Japanese Journal of Infectious Diseases
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