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  • Journals
  • Articles  (1,177)
  • Latest Papers from Table of Contents or Articles in Press  (1,177)
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  • Frontiers Media
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  • Journals
  • Articles  (1,177)
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  • Latest Papers from Table of Contents or Articles in Press  (1,177)
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  • Oxford University Press  (1,177)
  • American Chemical Society (ACS)
  • Frontiers Media
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  • 1
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    Association between age and repair of oxidatively damaged DNA in human peripheral blood mononuclear cells (2015)
    Oxford University Press
    Details
    Publication Date: 2015-08-20
    Description: It has been hypothesised that positive associations between age and levels of oxidative stress-generated damage to DNA may be related to an age-dependent decline in DNA repair activity. The objective of this study was to investigate the association between age and repair activity of oxidatively damaged DNA in peripheral blood mononuclear cells (PBMCs). We isolated PBMCs from subjects aged 18–83 years, as part of a health survey of the Danish population that focussed on lifestyle factors. The level of DNA repair activity was measured as incisions on potassium bromate-damaged DNA by the comet assay. There was an inverse association between age and DNA repair activity with a 0.65% decline in activity per year from age 18 to 83 (95% confidence interval: 0.16–1.14% per year). Univariate regression analysis also indicated inverse associations between DNA repair activity and waist-hip ratio ( P 〈 0.05) and plasma concentrations of glycosylated hemoglobin ( P = 0.07). However, multivariate regression analysis only showed an inverse association between age and DNA repair activity ( P 〈 0.05), indicating that the decline in repair activity was not mediated by metabolic risk factors. In summary, the results show an inverse association between age and DNA repair activity of oxidatively damaged DNA.
    Print ISSN: 0267-8357
    Electronic ISSN: 1464-3804
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 2
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    No oxidative stress or DNA damage in peripheral blood mononuclear cells after exposure to particles from urban street air in overweight elderly (2015)
    Oxford University Press
    Details
    Publication Date: 2015-08-20
    Description: Exposure to traffic-related particulate matter (PM) has been associated with increased risk of lung disease, cancer and cardiovascular disease especially in elderly and overweight subjects. The proposed mechanisms involve intracellular production of reactive oxygen species (ROS), inflammation and oxidation-induced DNA damage studied mainly in young normal-weight subjects. We performed a controlled cross-over, randomised, single-blinded, repeated-measure study where 60 healthy subjects (25 males and 35 females) with age 55–83 years and body mass index above 25kg/m 2 were exposed for 5h to either particle-filtered or sham-filtered air from a busy street with number of concentrations and PM 2.5 levels of 1800/cm 3 versus 23 000/cm 3 and 3 µg/m 3 versus 24 µg/m 3 , respectively. Peripheral blood mononuclear cells (PBMCs) were collected and assayed for production of ROS with and without ex vivo exposure to nanosized carbon black as well as expression of genes related to inflammation ( chemokine (C-C motif) ligand 2 , interleukin-8 and tumour necrosis factor ), oxidative stress response ( heme oxygenase (decycling)-1 ) and DNA repair ( oxoguanine DNA glycosylase ). DNA strand breaks and oxidised purines were assayed by the alkaline comet assay. No statistically significant differences were found for any biomarker immediately after exposure to PM from urban street air although strand breaks and oxidised purines combined were significantly associated with the particle number concentration during exposure. In conclusion, 5h of controlled exposure to PM from urban traffic did not change the gene expression related to inflammation, oxidative stress or DNA repair, ROS production or oxidatively damaged DNA in PBMCs from elderly overweight human subjects.
    Print ISSN: 0267-8357
    Electronic ISSN: 1464-3804
    Topics: Biology , Medicine
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  • 3
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    Sesamol attenuates genotoxicity in bone marrow cells of whole-body {gamma}-irradiated mice (2015)
    Oxford University Press
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    Publication Date: 2015-08-20
    Description: Ionising radiation causes free radical–mediated damage in cellular DNA. This damage is manifested as chromosomal aberrations and micronuclei (MN) in proliferating cells. Sesamol, present in sesame seeds, has the potential to scavenge free radicals; therefore, it can reduce radiation-induced cytogenetic damage in cells. The aim of this study was to investigate the radioprotective potential of sesamol in bone marrow cells of mice and related haematopoietic system against radiation-induced genotoxicity. A comparative study with melatonin was designed for assessing the radioprotective potential of sesamol. C57BL/6 mice were administered intraperitoneally with either sesamol or melatonin (10 and 20mg/kg body weight) 30min prior to 2-Gy whole-body irradiation (WBI) and sacrificed after 24h. Total chromosomal aberrations (TCA), MN and cell cycle analyses were performed using bone marrow cells. The comet assay was performed on bone marrow cells, splenocytes and lymphocytes. Blood was drawn to study haematological parameters. Prophylactic doses of sesamol (10 and 20mg/kg) in irradiated mice reduced TCA and micronucleated polychromatic erythrocyte frequency in bone marrow cells by 57% and 50%, respectively, in comparison with radiation-only groups. Sesamol-reduced radiation-induced apoptosis and facilitated cell proliferation. In the comet assay, sesamol (20mg/kg) treatment reduced radiation-induced comets (% DNA in tail) compared with radiation only ( P 〈 0.05). Sesamol also increased granulocyte populations in peripheral blood similar to melatonin. Overall, the radioprotective efficacy of sesamol was found to be similar to that of melatonin. Sesamol treatment also showed recovery of relative spleen weight at 24h of WBI. The results strongly suggest the radioprotective efficacy of sesamol in the haematopoietic system of mice.
    Print ISSN: 0267-8357
    Electronic ISSN: 1464-3804
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 4
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    The art of persistence--the secrets to Burkholderia chronic infections (2016)
    Oxford University Press
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    Publication Date: 2016-08-05
    Description: The Gram-negative proteobacteria genus Burkholderia encompasses multiple bacterial species that are pathogenic to humans and other vertebrates. Two pathogenic species of interest within this genus are Burkholderia pseudomallei (Bpm) and the B. cepacia complex (Bcc); the former is the causative agent of melioidosis in humans and other mammals, and the latter is associated with pneumonia in immunocompromised patients. One understudied and shared characteristic of these two pathogenic groups is their ability to persist and establish chronic infection within the host. In this review, we will explore the depth of knowledge about chronic infections caused by persistent Bpm and Bcc. We examine the host risk factors and immune responses associated with more severe chronic infections. We also discuss host adaptation and phenotypes associated with persistent Burkholderia species. Lastly, we survey how other intracellular bacteria associated with chronic infections are combatted and explore possible future applications to target Burkholderia . Our goal is to highlight understudied areas that should be addressed for a more thorough understanding of chronic Burkholderia infections and how to combat them.
    Print ISSN: 0928-8244
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 5
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    Comparative evaluation of in vitro human macrophage models for mycobacterial infection study (2016)
    Oxford University Press
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    Publication Date: 2016-07-13
    Description: Macrophages are phagocytic cells that play a key role maintaining the homeostasis of many tissues. Their function is essential for controlling and eradicating infecting mycobacteria. Human monocytic cell lines such as THP-1 and U937 have provided interesting insights into how mycobacteria subvert the host cell response. However, immortalized cell lines could bring some disadvantages. Here we compare the response of THP-1 and U937 cell lines with human monocyte-derived macrophages (hMDMs) to determine functional differences during infection with different mycobacterial phenotypes (virulent Mycobacterium tuberculosis H37Rv and Mycobacterium bovis , and attenuated M. bovis BCG). The findings of this study indicate that the U937 cell line displays a significantly lower phagocytic capacity than hMDMs and THP-1 macrophages, regardless of the mycobacterial strain. In all cell models, interferon- activation leads to up-regulation of interleukin-12 and nitrite production. However, the phorbol 12-myristate 13-acetate (PMA)-induced differentiation of U937 and THP-1 cell lines induces a significant tumor necrosis factor-α production in resting macrophages. However, this state of activation has no effect on the control of intracellular growth of mycobacteria. Moreover, U937 cells show more discrepancies with hMDM than THP-1. This study demonstrates that THP-1 macrophages exhibit closer functional similarities to hMDMs in response to mycobacterial infection, regardless of the strain.
    Print ISSN: 0928-8244
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 6
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    Protein-based profiling of the immune response to uropathogenic Escherichia coli in adult patients immediately following hospital admission for acute cystitis (2016)
    Oxford University Press
    Details
    Publication Date: 2016-07-13
    Description: Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) are common infections in humans. Despite the substantial healthcare cost represented by these infections, the human immune response associated with the infection immediately following the onset of symptoms in patients remains largely undefined. We performed a prospective study aimed at defining the milieu of urinary cytokines in adult inpatients in the 24–48 h period immediately following hospital admission for acute cystitis due to UPEC. Urine samples, analyzed using 27-target multiplex protein assays, were used to generate immune profiles for patients and compared to age- and gender-matched healthy controls. The levels of multiple pro-inflammatory cytokines were significantly elevated in urine as a result of infection, an observation consistent with prior findings in murine models and clinical literature. We also identified significant responses for several novel factors not previously associated with the human response to UTI, including Interleukin (IL)-4, IL-7, IL-9, IL-17A, eotaxin, Granulocyte-macrophage colony-stimulating factor (GM-CSF) and several growth factors. These data establish crucial parallels between the human immune response to UPEC and murine model UTI studies, and emphasize the complex but poorly defined nature of the human immune response to UPEC, particularly in the immediate period following the onset of symptoms for acute cystitis.
    Print ISSN: 0928-8244
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 7
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    Neutrophil-generated oxidative stress and protein damage in Staphylococcus aureus (2016)
    Oxford University Press
    Details
    Publication Date: 2016-07-13
    Description: Staphylococcus aureus is a ubiquitous, versatile and dangerous pathogen. It colonizes over 30% of the human population, and is one of the leading causes of death by an infectious agent. During S. aureus colonization and invasion, leukocytes are recruited to the site of infection. To combat S. aureus , leukocytes generate an arsenal of reactive species including superoxide, hydrogen peroxide, nitric oxide and hypohalous acids that modify and inactivate cellular macromolecules, resulting in growth defects or death. When S. aureus colonization cannot be cleared by the immune system, antibiotic treatment is necessary and can be effective. Yet, this organism quickly gains resistance to each new antibiotic it encounters. Therefore, it is in the interest of human health to acquire a deeper understanding of how S. aureus evades killing by the immune system. Advances in this field will have implications for the design of future S. aureus treatments that complement and assist the host immune response. In that regard, this review focuses on how S. aureus avoids host-generated oxidative stress, and discusses the mechanisms used by S. aureus to survive oxidative damage including antioxidants, direct repair of damaged proteins, sensing oxidant stress and transcriptional changes. This review will elucidate areas for studies to identify and validate future antimicrobial targets.
    Print ISSN: 0928-8244
    Topics: Biology , Medicine
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  • 8
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    Control of autoimmune inflammation by celastrol, a natural triterpenoid (2016)
    Oxford University Press
    Details
    Publication Date: 2016-07-27
    Description: Celastrol is a bioactive compound derived from traditional Chinese medicinal herbs of the Celastraceae family. Celastrol is known to possess anti-inflammatory and anti-oxidant activities. Our studies have highlighted the immunomodulatory attributes of celastrol in adjuvant-induced arthritis (AA), an experimental model of human rheumatoid arthritis (RA). RA is an autoimmune disease characterized by chronic inflammation of the synovial lining of the joints, leading eventually to tissue damage and deformities. Identification of the molecular targets of celastrol such as the NF-B pathway, MAPK pathway, JAK/STAT pathway and RANKL/OPG pathway has unraveled its strategic checkpoints in controlling arthritic inflammation and tissue damage in AA. The pathological events that are targeted and rectified by celastrol include increased production of pro-inflammatory cytokines; an imbalance between pathogenic T helper 17 and regulatory T cells; enhanced production of chemokines coupled with increased migration of immune cells into the joints; and increased release of mediators of osteoclastic bone damage. Accordingly, celastrol is a promising candidate for further testing in the clinic for RA therapy. Furthermore, the results of other preclinical studies suggest that celastrol might also be beneficial for the treatment of a few other autoimmune diseases besides arthritis.
    Print ISSN: 0928-8244
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 9
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    Identification of a virulence determinant that is conserved in the Jawetz and Heyl biotypes of [Pasteurella] pneumotropica (2016)
    Oxford University Press
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    Publication Date: 2016-08-05
    Description: [ Pasteurella ] pneumotropica is a ubiquitous bacterium frequently isolated from laboratory rodents. Although this bacterium causes various diseases in immunosuppressed animals, little is known about major virulence factors and their roles in pathogenicity. To identify virulence factors, we sequenced the genome of [ P. ] pneumotropica biotype Heyl strain ATCC 12555, and compared the resulting non-contiguous draft genome sequence with the genome of biotype Jawetz strain ATCC 35149. Among a large number of genes encoding virulence-associated factors in both strains, four genes encoding for YadA-like proteins, which are known virulence factors that function in host cell adherence and invasion in many pathogens. In this study, we assessed YadA distribution and biological activity as an example of one of virulence–associated factor shared, with biotype Jawetz and Heyl. More than half of mouse isolates were found to have at least one of these genes; whereas, the majority of rat isolates did not. Autoagglutination activity, and ability to bind to mouse collagen type IV and mouse fibroblast cells, was significantly higher in YadA-positive than YadA-negative strains. To conclude, we identified a large number of candidate genes predicted to influence [ P. ] pneumotropica pathogenesis.
    Print ISSN: 0928-8244
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 10
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    Synergistic activity between an antimicrobial polyacrylamide and daptomycin versus Staphylococcus aureus biofilm (2016)
    Oxford University Press
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    Publication Date: 2016-07-08
    Description: Antibiotic resistance of bacteria growing in biofilms compared to their planktonic counterparts enhances the difficulty to eradicate biofilm-associated infections. In the last decade, combination antibiotic therapy has emerged as an attractive strategy for treating biofilm infections, even if in most of tolerant biofilms the optimal combinations are still unknown. In this study, an antimicrobial cationic polyacrylamide was used in combination with daptomycin or moxifloxacin against mature biofilms of Staphylococcus aureus clinical isolates to examine a possible improvement of the antibiofilm activity of the two antibiotics. The polymer did not have an effect on moxifloxacin but significantly increased the antibiofilm efficacy of daptomycin. These findings are presumably related to the different mechanism of action of the two drugs. In summary, our data highlighted the ability of polycations to increase daptomycin antibiofilm activity providing a potential strategy to eradicate biofilms in industrial or medical settings.
    Print ISSN: 0928-8244
    Topics: Biology , Medicine
    Published by Oxford University Press
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