It is generally agreed that reactive oxygen species (ROS) contribute to skin aging, skin disorders, and skin diseases. Skin possesses an extremely efficient antioxidant system. This antioxidant activity is conferred by two systems: antioxidant enzymes and small molecules that can scavenge ROS by donating electrons. No gene-encoded secreted ROS scavengers have been reported. Amphibian skin is a multifunctional organ acting in defense, respiration, and water regulation, although it seems susceptible. Amphibian skins are easily harmed by biological or nonbiological attacks such as microorganism infection or radiation injury. Among vertebrates, skins of amphibian are exposed to more dangers of radiation injury than others. Radiation toxicity occurs by directly attacking the genetic material and/or by generating ROS. In addition, amphibian skin respiration and inflammatory response also induce ROS generation. It is rational to hypothesize that amphibian skins should have potent free radical scavenging and radioprotective ability for their survival. Rana pleuraden is distributed in Southwest of China; it lives in the subtropical plateau (altitude around 2300 m) where there is strong ultraviolet radiation and long duration of sunshine. By peptidomics and genomics approaches, a large amount of antioxidant peptides belonging to 11 different groups with variable structures were isolated from the skin secretions of R. pleuraden. Their free radical scavenging and anti-inflammatory abilities were studied. All of these peptide share highly homologous preproregions, although mature antioxidant peptides have very divergent primary structures, suggesting the possibility of a common ancestor. Some peptides were also found to have multifunctional properties, such as combined antioxidant, anti-inflammatory, and antimicrobial activities. According to our knowledge, no gene-encoded specific antioxidant peptides have been reported except metallothionein. Our work possibly reveals a new skin antioxidant system. The current work also provides a large amount of peptide candidates with medical-pharmaceutical significance. Molecular & Cellular Proteomics 8: 571-583, 2009.
Objective Acinetobacter baumannii is considered the prototypical example of a multi- or pan- drug-resistant bacterium. It has been increasingly implicated as a major cause of nosocomial and community-associated infections. This study proposed to evaluate the efficacy of immunological approaches to prevent and treat A. baumannii infections.MethodsMice were immunized with outer membrane vesicles (OMVs) prepared from a clinically isolated multidrug-resistant strain of A. baumannii. Pneumonia and sepsis models were used to evaluate the efficacy of active and passive immunization with OMVs. The probable effective mechanisms and the protective potential of clonally distinct clinical isolates were investigated in vitro using an opsonophagocytic assay.ResultsIntramuscular immunization with OMVs rapidly produced high levels of OMV-specific IgG antibodies, and subsequent intranasal challenge with A. baumannii elicited mucosal IgA and IgG responses. Both active and passive immunization protected the mice from challenges with homologue bacteria in a sepsis model. Bacterial burden in bronchoalveolar lavage fluids (BALF), lung, and spleen, inflammatory cell infiltration in BALF and lung, and inflammatory cytokine accumulation in BALF was significantly suppressed in the pneumonia model by both active and passive immunization strategies. The antisera from immunized mice presented with significant opsonophagocytic activities in a dose-dependent manner against not only homologous strains but also five of the other six clonally distinct clinical isolates.ConclusionsUtilizing immunological characteristics of outer membrane proteins to elevate protective immunity and circumvent complex multidrug-resistance mechanisms might be a viable approach to effectively control A. baumannii infections.
Since its emergence in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has developed into a global pandemic within a matter of months. While subunit vaccines are one of the prominent options for combating coronavirus disease 2019 (COVID‐19), the immunogenicity of spike protein‐based antigens remains unknown. When immunized in mice, the S1 domain induced much higher IgG and IgA antibody levels than the RBD and more efficiently neutralized SARS‐CoV‐2 when adjuvanted with alum. It is inferred that a large proportion of these neutralization epitopes are located in the S1 domain but outside the RBD and that some of these are spatial epitopes. This finding indicates that expression systems with posttranslational modification abilities are important to maintain the natural configurations of recombinant spike protein antigens and are critical for effective COVID‐19 vaccines. Further, adjuvants prone to a Th1 response should be considered for S1‐based subunit COVID‐19 vaccines to reduce the potential risk of antibody‐dependent enhancement (ADE) of infection. This article is protected by copyright. All rights reserved.
A. baumannii infections are becoming more and more serious health issues with rapid emerging of multidrug and extremely drug resistant strains, and therefore, there is an urgent need for the development of nonantibiotic-based intervention strategies. This study aimed at identifying whether an outer membrane protein with molecular weight of about 22 kDa (Omp22) holds the potentials to be an efficient vaccine candidate and combat A. baumannii infection. Omp22 which has a molecule length of 217 amino acids kept more than 95% conservation in totally 851 reported A. baumannii strains. Recombinant Omp22 efficiently elicited high titers of specific IgG in mice. Both active and passive immunizations of Omp22 increased the survival rates of mice, suppressed the bacterial burdens in the organs and peripheral blood, and reduced the levels of serum inflammatory cytokines and chemokines. Opsonophagocytosis assays showed in vitro that Omp22 antiserum had highly efficient bactericidal activities on clonally distinct clinical A. baumannii isolates, which were partly complements-dependent and opsonophagocytic killing effects. Additionally, administration with as high as 500 μg of Omp22 didn’t cause obvious pathological changes in mice. In conclusion, Omp22 is a novel conserved and probably safe antigen for developing effective vaccines or antisera to control A. baumannii infections.
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