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Host–Biofilm Interactions at Mucosal Surfaces and Implications in Human Health
Published in Chaminda Jayampath Seneviratne, Microbial Biofilms, 2017
Nityasri Venkiteswaran, Kassapa Ellepola, Chaminda Jayampath Seneviratne, Yuan Kun Lee, Kia Joo Puan, Siew Cheng Wong
In humans, a wide variety of proteins and peptides exhibit antimicrobial activity. Host-derived antimicrobial peptides (AMPs) form an essential part of the innate immune system. Defensins were the first natural antimicrobial peptides to be described in mammalian cells. Originally isolated from epithelial cells and neutrophils, they are small cationic peptides and function by binding to the bacterial plasma membrane. Defensins cause a disruption of the membrane integrity resulting in inhibition of DNA, RNA and protein synthesis. The nature of the interaction allows defensins to target both Gram-positive and Gram-negative bacteria, fungi and enveloped viruses. Two classes of defensins have been described in humans, alpha and beta. Both types consist of six conserved cysteine residues. Alpha-defensins are synthesised by polymorphonuclear leukocytes and Paneth cells. In contrast to alpha-defensins, beta-defensins are secreted by epithelial cells in the respiratory, gastrointestinal and urinary tracts. Defensins are secreted at low levels under normal physiological conditions but can be induced in response to microbial infections. Since their discovery, other functional roles have been ascribed to defensins [139]. For instance, alpha-defensins such as HNP1-3 have been demonstrated to function as chemoattractants for dendritic cells and naïve CD4 and CD8 T cells [140]. Alpha-defensins derived from human neutrophils have been shown to neutralise the anthrax lethal toxin [141], diphtheria toxin and Pseudomonas exotoxin A [141]. Recent investigations on human beta-defensin-3 have revealed its link to oral cancer [142].
Immunoinformatics-guided designing and in silico analysis of epitope-based polyvalent vaccines against multiple strains of human coronavirus (HCoV)
Published in Expert Review of Vaccines, 2022
Bishajit Sarkar, Md. Asad Ullah, Yusha Araf, Nafisa Nawal Islam, Umme Salma Zohora
The best-selected epitopes were conjugated with each other to construct three possible vaccines. From these three vaccines, one best possible vaccine would be selected based on the molecular docking analysis. The CTL, HTL and BCL epitopes were conjugated by GGGGS, GPGPG, and KK linkers. Three vaccine constructs contained three different adjuvant sequences: L7/L12 ribosomal protein and HBHA protein (M.tuberculosis, accession number: AGV15514.1) and beta-defensin-3 (UniProt accession number: Q5U7J2), that were linked to the epitopes by EAAAK linkers. Adjuvants are known to enhance the antigenicity, immunogenicity, stability, and longevity of the constructed vaccines [48,49]. The vaccine constructs also contained the pan HLA-DR epitope (PADRE) sequence, attached with the adjuvant and epitopes. The EAAAK linkers provideeffective separation of domains of the bifunctional fusion proteins [50]. Again, the GPGPG linkers have the capability to prevent the generation of junctional epitopes and facilitate the immune processing and presentation [51]. Furthermore, the bi-lysine (KK) linkers preserve the independent immunological activities of the epitopes of a vaccine [52]. And the GGGGS is a flexible linker which was proved to be effective in conferring resistance to proteases [53].
Application of platelet-rich plasma in traumatic bone infections
Published in Expert Review of Anti-infective Therapy, 2021
Ruohui Tang, Shaochuan Wang, Jing Yang, Tong Wu, Jun Fei
In vitro studies have shown that PRP in the activated state has antibacterial effects on a variety of gram-positive and gram-negative bacteria [47]. The activation of PRP releases a variety of antimicrobial peptides, including platelet factor 4 (PF4), Platelet-activating factor (PAF), Macrophage inflammatory protein (MIP-1 α), and human beta defensin-3 (HBD-3). These biologically active factors exert their natural antibacterial effects in a variety of ways [48]. Specifically, Staphylococcus aureus is the most common pathogenic bacteria in TBIs, and HBD-3, which belongs to a class of natural antimicrobial peptides, has been shown to inhibit the proliferation of S. aureus [49]. In addition, transforming growth factor (TGF)-β and PDGF-BB in PRP also have definite inhibitory effects on the proliferation of S. aureus [50].
Impregnation of polyethylene terephthalate (PET) grafts with BMP-2 loaded functional nanoparticles for reconstruction of anterior cruciate ligament
Published in Journal of Microencapsulation, 2023
Zeynep Karahaliloglu, Batur Ercan, Baki Hazer
Microspheres or nanospheres, which are used into scaffolds as graft material, are accepted as excellent carrier for controlled release of drug content (Kim et al. 2014). Kempen et al. reported that the controlled and sustained release of BMP-2 improved ectopic osteogenic efficiency, and effective in long bone defect repair in situ (Kempen et al. 2009). Based on these informations, BMP-2 released from PLinaS-g-PEG-NPs at predetermined time intervals was detected, and shown in Figure 4(A). BMP-2 loaded nanoparticles, especially 0.1BMP2-PLinaS-g-PEG-NPs showed also a typical burst release within first day followed by sustained release that attributed to the growth factor at near particle surface causing a more rapid BMP-2 release, i.e. the higher BMP-2 concentration near the particle surface can be allow to rapidly pass to the release medium following the drug release rate slowed down (Kilicay et al., 2017). While the cumulative release percent of 0.05BMP2-PLinaS-g-PEG-NPs is 16 ± 0.86% after about 20 days, for 0.1BMP2-PLinaS-g-PEG-NPs is 23 ± 0.98%. Furthermore, by increasing the ratio of BMP-2 in PLinaS-g-PEG-NPs, the more growth factor release is observed. In line with these findings, Zhang et al. prepared recombinant human bone morphogenetic protein-2 (rhBMP-2) loaded Poly(lactic-co-glycolic acid) (PLGA) microspheres with core–shell structures (Zhang et al. 2017). 972.59 ± 5.69, 1618.66 ± 14.59 and 2587.95 ± 32.56 ng/mL was released from PLGA microspheres loaded with different concentrations of rhBMP-2 (12, 24 ve 48 µg/mL) after 21 days. It means that the release rate increased by BMP-2 loading efficiency. If here we compare our results with those of reports, He et al. fabricated scaffolds consisting of bone morphogenetic Protein-2 and human Beta Defensin-3 by 3D printer technology (He et al. 2021). These scaffolds displayed a release rate with 35% during 30 days, while a sustained release of rhBMP-2 loaded in a PLinaS-g-PEG carrier with 23% of cumulative release rate was obtained for 20 days in this study. Therefore, the obtained release values seem satisfactory when it considered that BMP-2 is effective for bone tissue regeneration in ACL injuries.