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  1. Article ; Online: Senescent cell-derived extracellular vesicles as potential mediators of innate immunosenescence and inflammaging.

    Hanley, Shaun / Chen, Yung-Yi / Hazeldine, Jon / Lord, Janet M

    Experimental gerontology

    2024  Volume 187, Page(s) 112365

    Abstract: Ageing is accompanied by a decline in immune function (immunosenescence), increased inflammation (inflammaging), and more senescent cells which together contribute to age-related disease and infection susceptibility. The innate immune system is the front- ...

    Abstract Ageing is accompanied by a decline in immune function (immunosenescence), increased inflammation (inflammaging), and more senescent cells which together contribute to age-related disease and infection susceptibility. The innate immune system is the front-line defence against infection and cancer and is also involved in the removal of senescent cells, so preventing innate immunosenescence and inflammaging is vital for health in older age. Extracellular vesicles (EVs) modulate many aspects of innate immune function, including chemotaxis, anti-microbial responses, and immune regulation. Senescent cell derived EVs (SEVs) have different cargo to that of non-senescent cell derived EVs, suggesting alterations in EV cargo across the lifespan may influence innate immune function, possibly contributing to immunosenescence and inflammaging. Here we review current understanding of the potential impact of miRNAs, lipids and proteins, found in higher concentrations in SEVs, on innate immune functions and inflammation to consider whether SEVs are potential influencers of innate immunosenescence and inflammaging. Furthermore, senolytics have demonstrated an ability to return plasma EV content closer to that of non-senescent EVs, therefore the potential use of senotherapeutics (senolytics and senostatics) to ameliorate the effects of SEVs on immunosenescence and inflammaging is also considered as a possible strategy for extending health-span in older adults.
    MeSH term(s) Humans ; Aged ; Senotherapeutics ; Immunosenescence/physiology ; Aging/physiology ; Inflammation/metabolism ; Extracellular Vesicles/metabolism ; Cellular Senescence/physiology
    Chemical Substances Senotherapeutics
    Language English
    Publishing date 2024-01-24
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 390992-x
    ISSN 1873-6815 ; 0531-5565
    ISSN (online) 1873-6815
    ISSN 0531-5565
    DOI 10.1016/j.exger.2024.112365
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    In stock of ZB MED Cologne/Königswinter

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  2. Article ; Online: The immune suppressive properties of damage associated molecular patterns in the setting of sterile traumatic injury.

    Horner, Emily / Lord, Janet M / Hazeldine, Jon

    Frontiers in immunology

    2023  Volume 14, Page(s) 1239683

    Abstract: Associated with the development of hospital-acquired infections, major traumatic injury results in an immediate and persistent state of systemic immunosuppression, yet the underlying mechanisms are poorly understood. Detected in the circulation in the ... ...

    Abstract Associated with the development of hospital-acquired infections, major traumatic injury results in an immediate and persistent state of systemic immunosuppression, yet the underlying mechanisms are poorly understood. Detected in the circulation in the minutes, days and weeks following injury, damage associated molecular patterns (DAMPs) are a heterogeneous collection of proteins, lipids and DNA renowned for initiating the systemic inflammatory response syndrome. Suggesting additional immunomodulatory roles in the post-trauma immune response, data are emerging implicating DAMPs as potential mediators of post-trauma immune suppression. Discussing the results of
    MeSH term(s) Humans ; Immunosuppression Therapy ; Infertility ; Immunomodulation ; Alarmins ; Cross Infection
    Chemical Substances Alarmins
    Language English
    Publishing date 2023-08-15
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1239683
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Neutrophils and COVID-19: Active Participants and Rational Therapeutic Targets.

    Hazeldine, Jon / Lord, Janet M

    Frontiers in immunology

    2021  Volume 12, Page(s) 680134

    Abstract: Whilst the majority of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of COVID-19, experience mild to moderate symptoms, approximately 20% develop severe respiratory complications that may ... ...

    Abstract Whilst the majority of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of COVID-19, experience mild to moderate symptoms, approximately 20% develop severe respiratory complications that may progress to acute respiratory distress syndrome, pulmonary failure and death. To date, single cell and high-throughput systems based analyses of the peripheral and pulmonary immune responses to SARS-CoV-2 suggest that a hyperactive and dysregulated immune response underpins the development of severe disease, with a prominent role assigned to neutrophils. Characterised in part by robust generation of neutrophil extracellular traps (NETs), the presence of immature, immunosuppressive and activated neutrophil subsets in the circulation, and neutrophilic infiltrates in the lung, a granulocytic signature is emerging as a defining feature of severe COVID-19. Furthermore, an assessment of the number, maturity status and/or function of circulating neutrophils at the time of hospital admission has shown promise as a prognostic tool for the early identification of patients at risk of clinical deterioration. Here, by summarising the results of studies that have examined the peripheral and pulmonary immune response to SARS-CoV-2, we provide a comprehensive overview of the changes that occur in the composition, phenotype and function of the neutrophil pool in COVID-19 patients of differing disease severities and discuss potential mediators of SARS-CoV-2-induced neutrophil dysfunction. With few specific treatments currently approved for COVID-19, we conclude the review by discussing whether neutrophils represent a potential therapeutic target for the treatment of patients with severe COVID-19.
    MeSH term(s) COVID-19/immunology ; Extracellular Traps/immunology ; Humans ; Neutrophils/immunology ; SARS-CoV-2/immunology
    Language English
    Publishing date 2021-06-02
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.680134
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Immunesenescence: A Predisposing Risk Factor for the Development of COVID-19?

    Hazeldine, Jon / Lord, Janet M

    Frontiers in immunology

    2020  Volume 11, Page(s) 573662

    Abstract: Bearing a strong resemblance to the phenotypic and functional remodeling of the immune system that occurs during aging (termed immunesenescence), the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of ... ...

    Abstract Bearing a strong resemblance to the phenotypic and functional remodeling of the immune system that occurs during aging (termed immunesenescence), the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), is characterized by an expansion of inflammatory monocytes, functional exhaustion of lymphocytes, dysregulated myeloid responses and the presence of highly activated senescent T cells. Alongside advanced age, male gender and pre-existing co-morbidities [e.g., obesity and type 2 diabetes (T2D)] are emerging as significant risk factors for COVID-19. Interestingly, immunesenescence is more profound in males when compared to females, whilst accelerated aging of the immune system, termed premature immunesenescence, has been described in obese subjects and T2D patients. Thus, as three distinct demographic groups with an increased susceptibility to COVID-19 share a common immune profile,
    MeSH term(s) Aging/immunology ; Betacoronavirus/immunology ; COVID-19 ; Cellular Senescence/immunology ; Coronavirus Infections/immunology ; Coronavirus Infections/pathology ; Diabetes Mellitus, Type 2/immunology ; Female ; Humans ; Male ; Monocytes/immunology ; Neutrophils/immunology ; Obesity/immunology ; Pandemics ; Pneumonia, Viral/immunology ; Pneumonia, Viral/pathology ; Risk Factors ; SARS-CoV-2 ; T-Lymphocytes/immunology
    Keywords covid19
    Language English
    Publishing date 2020-10-06
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.573662
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Circulating myeloid populations have prognostic utility in alcohol-related liver disease.

    Khan, Reenam / Salman, Shees / Harford, Laura / Sheriff, Lozan / Hazeldine, Jon / Rajoriya, Neil / Newsome, Philip N / Lalor, Patricia F

    Frontiers in immunology

    2024  Volume 15, Page(s) 1330536

    Abstract: Introduction: Alcohol-related liver disease (ARLD) accounts for over one third of all deaths from liver conditions, and mortality from alcohol-related liver disease has increased nearly five-fold over the last 30 years. Severe alcohol-related hepatitis ... ...

    Abstract Introduction: Alcohol-related liver disease (ARLD) accounts for over one third of all deaths from liver conditions, and mortality from alcohol-related liver disease has increased nearly five-fold over the last 30 years. Severe alcohol-related hepatitis almost always occurs in patients with a background of chronic liver disease with extensive fibrosis or cirrhosis, can precipitate 'acute on chronic' liver failure and has a high short-term mortality. Patients with alcohol-related liver disease have impaired immune responses, and increased susceptibility to infections, thus prompt diagnosis of infection and careful patient management is required. The identification of early and non-invasive diagnostic and prognostic biomarkers in ARLD remains an unresolved challenge. Easily calculated predictors of infection and mortality are required for use in patients who often exhibit variable symptoms and disease severity and may not always present in a specialized gastroenterology unit.
    Methods: We have used a simple haematological analyser to rapidly measure circulating myeloid cell parameters across the ARLD spectrum.
    Results and discussion: We demonstrate for the first time that immature granulocyte (IG) counts correlate with markers of disease severity, and our data suggests that elevated counts are associated with increased short-term mortality and risk of infection. Other myeloid populations such as eosinophils and basophils also show promise. Thus IG count has the potential to serve alongside established markers such as neutrophil: lymphocyte ratio as a simply calculated predictor of mortality and risk of infectious complications in patients with alcohol-related hepatitis. This would allow identification of patients who may require more intensive management.
    MeSH term(s) Humans ; Prognosis ; Liver Diseases/complications ; Liver Cirrhosis/complications ; Hepatitis, Alcoholic ; Leukocyte Count
    Language English
    Publishing date 2024-03-13
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2024.1330536
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  6. Article ; Online: A combination nutritional supplement reduces DNA methylation age only in older adults with a raised epigenetic age.

    McGee, Kirsty C / Sullivan, Jack / Hazeldine, Jon / Schmunk, Lisa J / Martin-Herranz, Daniel E / Jackson, Thomas / Lord, Janet M

    GeroScience

    2024  

    Abstract: An increase in systemic inflammation (inflammaging) is one of the hallmarks of aging. Epigenetic (DNA methylation) clocks can quantify the degree of biological aging and this can be reversed by lifestyle and pharmacological intervention. We aimed to ... ...

    Abstract An increase in systemic inflammation (inflammaging) is one of the hallmarks of aging. Epigenetic (DNA methylation) clocks can quantify the degree of biological aging and this can be reversed by lifestyle and pharmacological intervention. We aimed to investigate whether a multi-component nutritional supplement could reduce systemic inflammation and epigenetic age in healthy older adults.We recruited 80 healthy older participants (mean age ± SD: 71.85 ± 6.23; males = 31, females = 49). Blood and saliva were obtained pre and post a 12-week course of a multi-component supplement, containing: Vitamin B3, Vitamin C, Vitamin D, Omega 3 fish oils, Resveratrol, Olive fruit phenols and Astaxanthin. Plasma GDF-15 and C-reactive protein (CRP) concentrations were quantified as markers of biological aging and inflammation respectively. DNA methylation was assessed in whole blood and saliva and used to derive epigenetic age using various clock algorithms.No difference between the epigenetic and chronological ages of participants was observed pre- and post-treatment by the blood-based Horvath or Hannum clocks, or the saliva-based InflammAge clock. However, in those with epigenetic age acceleration of ≥ 2 years at baseline, a significant reduction in epigenetic age (p = 0.015) and epigenetic age acceleration (p = 0.0058) was observed post-treatment using the saliva-based InflammAge clock. No differences were observed pre- and post-treatment in plasma GDF-15 and CRP, though participants with CRP indicative of an elevated cardiovascular disease risk (hsCRP ≥ 3µg/ml), had a reduction in CRP post-supplementation (p = 0.0195).Our data suggest a possible benefit of combined nutritional supplementation in individuals with an accelerated epigenetic age and inflammaging.
    Language English
    Publishing date 2024-03-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2886586-8
    ISSN 2509-2723 ; 2509-2715
    ISSN (online) 2509-2723
    ISSN 2509-2715
    DOI 10.1007/s11357-024-01138-8
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1502: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  7. Article ; Online: Immunesenescence

    Jon Hazeldine / Janet M. Lord

    Frontiers in Immunology, Vol

    A Predisposing Risk Factor for the Development of COVID-19?

    2020  Volume 11

    Abstract: Bearing a strong resemblance to the phenotypic and functional remodeling of the immune system that occurs during aging (termed immunesenescence), the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of ... ...

    Abstract Bearing a strong resemblance to the phenotypic and functional remodeling of the immune system that occurs during aging (termed immunesenescence), the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), is characterized by an expansion of inflammatory monocytes, functional exhaustion of lymphocytes, dysregulated myeloid responses and the presence of highly activated senescent T cells. Alongside advanced age, male gender and pre-existing co-morbidities [e.g., obesity and type 2 diabetes (T2D)] are emerging as significant risk factors for COVID-19. Interestingly, immunesenescence is more profound in males when compared to females, whilst accelerated aging of the immune system, termed premature immunesenescence, has been described in obese subjects and T2D patients. Thus, as three distinct demographic groups with an increased susceptibility to COVID-19 share a common immune profile, could immunesenescence be a generic contributory factor in the development of severe COVID-19? Here, by focussing on three key aspects of an immune response, namely pathogen recognition, elimination and resolution, we address this question by discussing how immunesenescence may weaken or exacerbate the immune response to SARS-CoV-2. We also highlight how aspects of immunesenescence could render potential COVID-19 treatments less effective in older adults and draw attention to certain therapeutic options, which by reversing or circumventing certain features of immunesenescence may prove to be beneficial for the treatment of groups at high risk of severe COVID-19.
    Keywords aging ; COVID-19 ; immunesenescence ; immune dysfunction ; inflammaging ; SARS-Cov_2 ; Immunologic diseases. Allergy ; RC581-607 ; covid19
    Subject code 610
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Immunesenescence

    Hazeldine, Jon / Lord, Janet M.

    Frontiers in Immunology

    A Predisposing Risk Factor for the Development of COVID-19?

    2020  Volume 11

    Keywords covid19
    Publisher Frontiers Media SA
    Publishing country ch
    Document type Article ; Online
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.573662
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Dysfunctional neutrophil response in COVID-19 infection vary by subtype.

    Thein, Onn Shaun / Belchamber, Kylie / Hazeldine, Jon / Faniyi, Aduragbemi / Grudzinska, Frances / Hughes, Michael / Jasper, Alice / Yip, Kay Por / Crowley, Louise / Lugg, Sebastian / Sapey, Elizabeth / Parekh, Dhruv / Thickett, David / Scott, Aaron

    Clinical medicine (London, England)

    2024  Volume 23 Suppl 6, Page(s) 69–70

    MeSH term(s) Humans ; COVID-19 ; Neutrophils
    Language English
    Publishing date 2024-02-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 2048646-7
    ISSN 1473-4893 ; 1470-2118
    ISSN (online) 1473-4893
    ISSN 1470-2118
    DOI 10.7861/clinmed.23-6-s69
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5439: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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  10. Article ; Online: Dysfunctional neutrophil response in COVID-19 infection vary by subtype.

    Thein, Onn Shaun / Belchamber, Kylie / Hazeldine, Jon / Faniyi, Aduragbemi / Grudzinska, Frances / Hughes, Michael / Jasper, Alice / Yip, Kay Por / Crowley, Louise / Lugg, Sebastian / Sapey, Elizabeth / Parekh, Dhruv / Thickett, David / Scott, Aaron

    Clinical medicine (London, England)

    2024  Volume 23, Issue Suppl 6, Page(s) 69–70

    MeSH term(s) Humans ; COVID-19 ; Neutrophils
    Language English
    Publishing date 2024-01-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 2048646-7
    ISSN 1473-4893 ; 1470-2118
    ISSN (online) 1473-4893
    ISSN 1470-2118
    DOI 10.7861/clinmed.23-6-s69
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5439: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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