Characterisation of the ocular inflammatory response to AAV reveals divergence by sex and age

Molecular Therapy, Journal Year: 2025, Volume and Issue: 33(3), P. 1246 - 1263

Published: Jan. 18, 2025

Language: Английский

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Gene Therapy-Associated Uveitis (GTAU): Understanding and mitigating the adverse immune response in retinal gene therapy

Progress in Retinal and Eye Research, Journal Year: 2025, Volume and Issue: unknown, P. 101354 - 101354

Published: March 1, 2025

Retinal gene therapy using adeno-associated viral (AAV) vectors has been a groundbreaking step-change in the treatment of inherited retinal diseases (IRDs) and could also be used to treat more common such as age-related macular degeneration diabetic retinopathy. The delivery expression therapeutic transgenes eye is limited by innate adaptive immune responses against components vector product, which termed therapy-associated uveitis (GTAU). This clinically important intraocular inflammation lead irreversible loss cells, deterioration visual function reduced durability effect associated with costly one-off treatment. For achieve an improved efficacy safety profile for treating additional IRDs diseases, risk GTAU must minimised. We have collated insights from pre-clinical research, clinical trials, real-world implementation AAV-mediated help understand factors GTAU. draw attention emerging framework, includes patient demographics, construct, dose, route administration, choice immunosuppression regime. Importantly, we consider efforts date potential future strategies mitigate adverse response across each these domains. advocate targeted immunomodulatory approaches prevention based on better understanding underlying response.

Language: Английский

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Centenarians, semi and supercentenarians, COVID-19 and Spanish flu: a serological assessment to gain insight into the resilience of older centenarians to COVID-19

Immunity & Ageing, Journal Year: 2024, Volume and Issue: 21(1)

Published: June 27, 2024

Although it is well known that the older people have been most susceptible to COVID-19, there are conflicting data on susceptibility of centenarians. Two epidemiological study shown centenarians (> 101 years old at time 2020 pandemic peak) more resilient than remaining centenarians, suggesting this resilience might be linked 1918 Spanish Flu pandemic. To gain insight into matter, specifically whether SARS-CoV-2 infection they had affected by, we conducted a retrospective serological study. This examined serum samples from 33 encompassing semi- (aged > 104 < 110 years, N = 7) and supercentenarians 109 4), born between 1905 1922, against both H1N1 pseudotype virus.

Language: Английский

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Mid-life: a critical window for intervention during aging

Published: Jan. 14, 2025

Mid-life represents a pivotal period marked by profound physiological and metabolic transitions, increasing susceptibility to chronic diseases. This review explores the molecular systemic underpinnings of mid-life transition integrating insights from recent studies that elucidate aging-associated changes in plasma proteome, immune system, adipose tissue remodeling, cellular senescence. Nonlinear waves proteomic alterations have been identified as critical transitions inflammatory hormonal pathways. In addition, sex-specific aging trajectories linked adaptive immunity decline innate activation vulnerabilities mid-life. Moreover, tissue’s central role has established its early remodeling cytokine secretion drive stress. Furthermore, Glb1-2A-mCherry reporter introduced monitor aging, identifying crucial phase for cardiac hypertrophy senescence-induced inflammation. Collectively, these findings our understanding underscoring interplay between processes health, with emerging window intervention. also underscores biomarkers therapeutic strategies alleviate challenges mid-life, thereby promoting healthy aging.

Language: Английский

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A researcher's guide to studying sex differences in immune aging

Trends in Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Peripheral and central elevation of IL-8 in patients with Huntington’s disease

Molecular Immunology, Journal Year: 2025, Volume and Issue: 179, P. 84 - 93

Published: Feb. 10, 2025

Huntington's Disease (HD) is a debilitating neurodegenerative condition characterized by motor, cognitive and psychiatric abnormalities. Immune hyperactivity dysregulation are common in HD. In addition to the central nervous system, HD patients exhibit systemic innate immune activation inflammation, which has been shown contribute pathogenic effects of Huntingtin gene mutation. Upregulation inflammatory mediators including interferon gamma (IFN-γ) interleukin (IL)-8 observed animal disease models. However, studies on remain limited. this study, serum samples from 58 59 age- gender-matched healthy control individuals were analysed using bead-based assay, that enabled simultaneous measurement 13 cytokines chemokines. Additionally, publicly available transcriptomic data brain tissues controls examined. Our results confirm IL-8 protein levels significantly higher compared non-HD controls, with highest moderate group. group, we found significant positive correlations between both IL-17A IL-10. these not patients, where notably positively correlated pro-inflammatory markers IFNγ IL-23. Interestingly, demonstrated negative correlation parameters, CAG trinucleotide repeat expansion burden score. Furthermore, chemokines such as monocyte chemoattractant 1 (MCP-1; CCL2) same parameters. In-depth analysis bulk RNAseq, single-nucleus RNA-sequencing (snRNAseq) two key HD-affected regions- prefrontal cortex striatum revealed expression increased controls. Moreover, snRNAseq showed than predominant microglia. Overall, our findings support an upregulation HD, evident degenerating regions, peripheral blood samples. We identified unique immunological signatures associated severity provide potential biomarkers may reflect immune-pathological mechanisms patients.

Language: Английский

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Sex, Age, and Previous Herpes Zoster Infection Role on Adverse Events Following Immunization with Adjuvanted Recombinant Vaccine

Pathogens, Journal Year: 2025, Volume and Issue: 14(2), P. 195 - 195

Published: Feb. 15, 2025

Adverse events following immunizations (AEFIs) with recombinant zoster vaccine (RZV) are underexplored in fragile populations. This study aims to assess incidence, duration, and characteristics of AEFIs, focusing on the impact sex, age, prior Herpes Zoster (HZ) infection a frail population, including solid organ transplant recipients. We conducted an observational patients receiving RZV, AEFIs were classified as local or systemic analyzed for patterns across groups. showed that females had higher incidence (p = 0.02), both symptoms, such swelling +/- redness at site injection fatigue, after first second doses. Younger adults experienced more reactions, while older reported (e.g., swelling, p 0.01). Moreover, previous HZ exhibited dose (68% vs. 38%, 0.001). In conclusion, clinical history significantly influenced AEFI manifestations. Therefore, it is important personalize vaccination strategies populations, by tailored administration monitoring plans, especially individuals infection, improve safety patient outcomes.

Language: Английский

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Gender-differences in imaging phenotypes of osteoarthritis in the osteoarthritis initiative

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 20, 2025

In osteoarthritis (OA) research it is increasingly recognized that stratification according to disease phenotypes essential for optimizing treatment regimens. Gender-specific differences in clinical OA manifestations have been identified, and this analysis aimed assess whether these extend imaging phenotypes.From the Osteoarthritis Initiative database 2523 participants (1409 women 1114 men) with completed 3T MRI whole-organ magnetic resonance scores (WORMS) of right knee at baseline were included. Imaging assigned based on modified Rapid OsteoArthritis Eligibility Score: inflammatory, meniscus-cartilage, bone phenotype. Logistic regression was performed investigate effect gender phenotype, independent BMI, race, Kellgren & Lawrence (KL) grade level physical activity. Female independently associated lower odds meniscus-cartilage (OR 0.61, 95%CI 0.47-0.80, p < 0.001) but not inflammatory 1.04, 0.89-1.24, = 0.697) or subchondral phenotype 1.13, 0.95-1.36, 0.166). This difference highlights an opportunity future refinements better accommodate gender/sex trajectories while investigating different regimes OA.

Language: Английский

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Zinc deficiency as possible link between immunosenescence and age-related diseases

Immunity & Ageing, Journal Year: 2025, Volume and Issue: 22(1)

Published: May 19, 2025

Abstract As global life expectancy increases, research reveals a critical challenge in aging: the progressive deterioration of immune function, termed immunosenescence. This age-related decline is characterized by complex dysregulation responses, which leaves older adults increasingly vulnerable to infections, chronic inflammatory states, and various degenerative diseases. Without intervention, immunosenescence significantly contributes morbidity mortality among elderly, intensifying healthcare burdens diminishing quality on both individual societal levels. review explores essential role zinc, trace element for health, mitigating impact slowing cascade immunological dysfunctions associated with aging. By modulating activity key cells pathways, zinc supplementation emerges as promising approach strengthen immunity, reduce oxidative stress, counteract "inflammaging," state chronic, low-grade inflammation that accelerates tissue damage drives disease progression. Zinc’s involvement cellular defense repair mechanisms across system highlights its ability enhance cell functionality, resilience, adaptability, strengthening body's resistance infection manage stressors contribute diseases Indeed, has demonstrated potential improve decrease inflammation, mitigate risk conditions including diabetes, depression, cardiovascular disease, vision loss. Given prevalent barriers adequate intake adults, dietary limitations, decreased absorption, interactions medications, this underscores urgent need address deficiency aging populations. Recent findings zinc’s molecular effects health present practical, accessible intervention supporting healthier improving life. integrating into targeted strategies, public efforts may not only sustain immunity elderly but also extend healthy longevity, costs, potentially incidence strain systems worldwide.

Language: Английский

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Retrospective analysis of pembrolizumab-related adverse reactions and death outcomes based on the FAERS database

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: May 22, 2025

This study aimed to analyze the characteristics of adverse reactions in cancer patients treated with Pembrolizumab based on U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) database, assess risk factors fatality reports. The data was sourced from FAERS collecting event reports related 2013 June 2024. main analysis variables included gender, age, type, country, reporter reaction outcomes. Descriptive statistics, univariate analysis, multivariate Logistic regression models were used relationship between each variable fatal outcome. A total 46,883 collected, including 5,483 number events has been increasing since 2013, especially peaking 2022 2023. United States Japan had highest serious reported increased significantly 51-65 66-80 age groups. who died concentrated elderly group (≥ 65 years old), median treatment duration time pembrolizumab 17 days. Analysis showed that gender (OR = 0.75; 95%CI: 0.71-0.80, p < 0.01), 0.89; 0.84-0.96, ingredients count 1.92; 1.84-2.01, 0.01) associated pembrolizumab. are closely patient individual types. It is necessary strengthen monitoring high-risk groups such as clinical reduce

Language: Английский

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