Percorrer por autor "Bonassi, Stefano"
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- Association of inflammatory mediators with frailty status in older adults: results from a systematic review and meta-analysisPublication . Marcos-Pérez, Diego; Sánchez-Flores, María; Proietti, Stefania; Bonassi, Stefano; Costa, Solange; Teixeira, Joao Paulo; Fernández-Tajes, Juan; Pásaro, Eduardo; Laffon, Blanca; Valdiglesias, VanessaFrailty is a geriatric syndrome defined as a status of extreme vulnerability to stressors, leading to a higher risk of negative health-related outcomes. "Inflammaging", an age-related state of low-grade chronic inflammation, is characterized by an increased concentration of pro-inflammatory cytokines and acute phase proteins. Inflammaging has been postulated as an underlying mechanism of frailty, and several studies tested the relationship between frailty and concentration of inflammatory mediators. The aim of this systematic review and meta-analysis was to test whether inflammatory mediators are overproduced in frail older adults. Among the 758 articles identified in the literature search, 50 were included in the systematic review, and 39 in the three meta-analyses, i.e., C-reactive protein (CRP), interleukin 6 (IL6), and tumor necrosis factor α. To reduce heterogeneity, meta-analyses were restricted to studies identifying frailty by the Fried et al. [1] [J. Gerontol. A. Biol. Sci. Med. Sci. 56, M146-56] phenotypic criteria. Quantitative analyses measuring the association between frailty and biomarker concentrations showed significant differences when frail subjects were compared to non-frail and pre-frail subjects for CRP and IL6. This work established strong association between inflammatory biomarkers and frailty, confirming the role of age-related chronic inflammation in frailty development.
- DNA damage in circulating leukocytes measured with the comet assay may predict the risk of deathPublication . Bonassi, Stefano; Ceppi, Marcello; Møller, Peter; Azqueta, Amaya; Milić, Mirta; Neri, Monica; Brunborg, Gunnar; Godschalk, Roger; Koppen, Gudrun; Langie, Sabine A.S.; Teixeira, João Paulo; Bruzzone, Marco; Da Silva, Juliana; Benedetti, Danieli; Cavallo, Delia; Ursini, Cinzia Lucia; Giovannelli, Lisa; Moretti, Silvia; Riso, Patrizia; Del Bo’, Cristian; Russo, Patrizia; Dobrzyńska, Malgorzata; Goroshinskaya, Irina A.; Surikova, Ekaterina I.; Staruchova, Marta; Barančokova, Magdalena; Volkovova, Katarina; Kažimirova, Alena; Smolkova, Bozena; Laffon, Blanca; Valdiglesias, Vanessa; Pastor, Susana; Marcos, Ricard; Hernández, Alba; Gajski, Goran; Spremo-Potparević, Biljana; Živković, Lada; Boutet-Robinet, Elisa; Perdry, Hervé; Lebailly, Pierre; Perez, Carlos L.; Basaran, Nursen; Nemeth, Zsuzsanna; Safar, Anna; Dusinska, Maria; Collins, Andrew; Anderson, Diana; Andrade, Vanessa; Pereira, Cristiana Costa; Costa, Solange; Gutzkow, Kristine B.; Ladeira, Carina; Moretti, Massimo; Costa, Carla; Orlow, Irene; Rojas, Emilio; Pourrut, Bertrand; Kruszewski, Marcin; Knasmueller, Siegfried; Shaposhnikov, Sergey; Žegura, Bojana; Stopper, HelgaThe comet assay or single cell gel electrophoresis, is the most common method used to measure strand breaks and a variety of other DNA lesions in human populations. To estimate the risk of overall mortality, mortality by cause, and cancer incidence associated to DNA damage, a cohort of 2,403 healthy individuals (25,978 person-years) screened in 16 laboratories using the comet assay between 1996 and 2016 was followed-up. Kaplan-Meier analysis indicated a worse overall survival in the medium and high tertile of DNA damage (p < 0.001). The effect of DNA damage on survival was modelled according to Cox proportional hazard regression model. The adjusted hazard ratio (HR) was 1.42 (1.06-1.90) for overall mortality, and 1.94 (1.04-3.59) for diseases of the circulatory system in subjects with the highest tertile of DNA damage. The findings of this study provide epidemiological evidence encouraging the implementation of the comet assay in preventive strategies for non-communicable diseases.
- Impact of occupational exposure to wildfire events on systemic inflammatory biomarkers in Portuguese wildland firefightersPublication . Esteves, Filipa; Madureira, Joana; Barros, Bela; Alves, Sara; Pires, Joana; Martins, Sandra; Oliveira, Marta; Vaz, Josiana; Slezakova, Klara; Pereira, Maria do Carmo; Fernandes, Adília; Morais, Simone; Guimarães, João Tiago; Bonassi, Stefano; Teixeira, João Paulo; Costa, SolangeWhile occupational exposure as a firefighter is considered a dangerous occupation, research on the underlying mechanisms remains limited, particularly in wildland firefighters. Inflammation, a key effect of wildfire exposure, plays a significant role in the development of various diseases. The current study aims to investigate the impact of wildland firefighting exposure on the levels of pro-inflammatory systemic biomarkers. A pre-post study design investigated 59 wildland firefighters comparing data collected after participation in a wildfire event (Phase II) with data obtained before wildfire season (Phase I). Data on demographics, lifestyle, health and occupational-related factors were assessed. Exposure factors, such as fire combat (e.g., exposure duration), were also registered. Inflammatory biomarkers (i.e. interleukin-6 [IL-6], interleukin-8 [IL-8], tumor necrosis factor α [TNF-α] and high-sensitivity C-reactive protein [hs-CRP]) and hydroxylated polycyclic aromatic hydrocarbons metabolites (1-OHNaph+1-OHAce, 2-OHFlu, 1-OHPhen, 1-OHPyr) were analysed in blood and urine samples, respectively. Serum IL-8 and IL-6 levels were significantly increased after wildland fire combat. IL-8 levels were 2.62 times higher (95 % CI: 1.96-3.50; p < 0.01), whereas IL-6 levels were 1.25 times higher (95 % CI: 1.00-1.57; p = 0.04). Furthermore, IL-8 levels were significantly correlated with urinary 2-hydroxyfluorene levels and fire combat duration (>12 h). In addition, the mean hs-CRP level, in both phases, was above 3.0 mg/L, indicating a potential risk for cardiovascular events. Given the long-term health implications of firefighting occupational exposure, biomonitoring and early detection of occupational risks are essential for protecting firefighters' health. Protective measures must be urgently implemented to enhance occupational health and strengthen preventive strategies in this sector.
- Lifestyle, environment and other major determinants of frailty in older adults: a population-based study from the UK BiobankPublication . Hemadeh, Ali; Lema-Arranz, Carlota; Bonassi, Stefano; Buscarini, Leonardo; Infarinato, Francesco; Romano, Paola; Finti, Alessia; Marinozzi, Franco; Bini, Fabiano; Fernández-Bertólez, Natalia; Teixeira, João Paulo; Lorenzo-López, Laura; Valdiglesias, Vanessa; Laffon, BlancaFrailty is a geriatric multidimensional syndrome characterized by a loss of physiologic reserves and disproportionate vulnerability to external stressors and associated with increased risk of multiple negative health outcomes. Since frailty can be prevented, controlled, and even reverted in its early stages, identifying the main factors involved in its development is crucial to implement preventive and/or restorative interventions. The aim of this study was to assess the impact of a broad range of parameters, including host factors, lifestyle, diet, and environmental and occupational conditions, on the development of frailty in later life. A cross-sectional study was conducted on 221,896 individuals aged 60 and over classified as non-frail (119,332, 53.8%), pre-frail (93,180, 42.0%), and frail (9384, 4.2%) according to the frailty phenotype. Using principal component analysis and machine learning to streamline the data, significant associations were found between frailty risk and air quality, diet, smoking, working conditions, and heavy alcohol consumption. Early-life factors, including breastfed as a baby and maternal smoking around birth, also emerged as predictors of frailty, which was further characterized by clinical indicators like polypharmacy, levels of C-reactive protein and other biomarkers of inflammageing. This study provided robust and original evidence on the association between a large battery of potential risk factors, from early to later stages of life, and the occurrence of frailty in older age. These results will contribute to the development of effective prevention strategies and facilitate the early detection of individuals at high risk of developing frailty.
- Low Vitamin D Levels and Frailty Status in Older Adults: A Systematic Review and Meta-AnalysisPublication . Marcos-Pérez, Diego; Sánchez-Flores, María; Proietti, Stefania; Bonassi, Stefano; Costa, Solange; Teixeira, Joao Paulo; Fernández-Tajes, Juan; Pásaro, Eduardo; Valdiglesias, Vanessa; Laffon, BlancaSerum vitamin D deficiency is widespread among older adults and is a potential modifiable risk factor for frailty. Moreover, frailty has been suggested as an intermediate step in the association between low levels of vitamin D and mortality. Hence, we conducted a systematic review of the literature and meta-analysis to test the possible association of low concentrations of serum 25-hydroxyvitamin D (25(OH)D), a marker of vitamin D status, with frailty in later life. We reviewed cross-sectional or longitudinal studies evaluating populations of older adults and identifying frailty by a currently validated scale. Meta-analyses were restricted to cross-sectional data from studies using Fried’s phenotype to identify frailty. Twenty-six studies were considered in the qualitative synthesis, and thirteen studies were included in the meta-analyses. Quantitative analyses showed significant differences in the comparisons of frail (standardized mean difference (SMD)—1.31, 95% confidence interval (CI) (−2.47, −0.15), p = 0.0271) and pre-frail (SMD—0.79, 95% CI (−1.58, −0.003), p = 0.0491) subjects vs. non-frail subjects. Sensitivity analyses reduced heterogeneity, resulting in a smaller but still highly significant between-groups difference. Results obtained indicate that lower 25(OH)D levels are significantly associated with increasing frailty severity. Future challenges include interventional studies testing the possible benefits of vitamin D supplementation in older adults to prevent/palliate frailty and its associated outcomes.
- Measuring DNA modifications with the comet assay: a compendium of protocolsPublication . Collins, Andrew; Møller, Peter; Gajski, Goran; Vodenková, Soňa; Abdulwahed, Abdulhadi; Anderson, Diana; Bankoglu, Ezgi Eyluel; Bonassi, Stefano; Boutet-Robinet, Elisa; Brunborg, Gunnar; Chao, Christy; Cooke, Marcus S.; Costa, Carla; Costa, Solange; Dhawan, Alok; de Lapuente, Joaquin; Bo’, Cristian Del; Dubus, Julien; Dusinska, Maria; Duthie, Susan J.; Yamani, Naouale El; Engelward, Bevin; Gaivão, Isabel; Giovannelli, Lisa; Godschalk, Roger; Guilherme, Sofia; Gutzkow, Kristine B.; Habas, Khaled; Hernández, Alba; Herrero, Oscar; Isidori, Marina; Jha, Awadhesh N.; Knasmüller, Siegfried; Kooter, Ingeborg M.; Koppen, Gudrun; Kruszewski, Marcin; Ladeira, Carina; Laffon, Blanca; Larramendy, Marcelo; Hégarat, Ludovic Le; Lewies, Angélique; Lewinska, Anna; Liwszyc, Guillermo E.; de Cerain, Adela López; Manjanatha, Mugimane; Marcos, Ricard; Milić, Mirta; de Andrade, Vanessa Moraes; Moretti, Massimo; Muruzabal, Damian; Novak, Matjaž; Oliveira, Rui; Olsen, Ann-Karin; Owiti, Norah; Pacheco, Mário; Pandey, Alok K.; Pfuhler, Stefan; Pourrut, Bertrand; Reisinger, Kerstin; Rojas, Emilio; Rundén-Pran, Elise; Sanz-Serrano, Julen; Shaposhnikov, Sergey; Sipinen, Ville; Smeets, Karen; Stopper, Helga; Teixeira, João Paulo; Valdiglesias, Vanessa; Valverde, Mahara; van Acker, Frederique; van Schooten, Frederik-Jan; Vasquez, Marie; Wentzel, Johannes F.; Wnuk, Maciej; Wouters, Annelies; Žegura, Bojana; Zikmund, Tomas; Langie, Sabine A.S.; Azqueta, AmayaThe comet assay is a versatile method to detect nuclear DNA damage in individual eukaryotic cells, from yeast to human. The types of damage detected encompass DNA strand breaks and alkali-labile sites (e.g., apurinic/apyrimidinic sites), alkylated and oxidized nucleobases, DNA-DNA crosslinks, UV-induced cyclobutane pyrimidine dimers and some chemically induced DNA adducts. Depending on the specimen type, there are important modifications to the comet assay protocol to avoid the formation of additional DNA damage during the processing of samples and to ensure sufficient sensitivity to detect differences in damage levels between sample groups. Various applications of the comet assay have been validated by research groups in academia, industry and regulatory agencies, and its strengths are highlighted by the adoption of the comet assay as an in vivo test for genotoxicity in animal organs by the Organisation for Economic Co-operation and Development. The present document includes a series of consensus protocols that describe the application of the comet assay to a wide variety of cell types, species and types of DNA damage, thereby demonstrating its versatility.
- Micronucleus assay in buccal and urothelial epithelial cells of wildland firefighters exposed to wildfire smokePublication . Esteves, Filipa; Madureira, Joana; Barros, Bela; Alves, Sara; Vaz, Josiana; Oliveira, Marta; Slezakova, Klara; Fernandes, Adília; do Carmo Pereira, Maria; Morais, Simone; Bonassi, Stefano; Teixeira, João Paulo; Costa, SolangeOccupational exposure as a firefighter is classified as carcinogenic to humans. However, information on the biological effects of wildland firefighting remains limited. This study aimed to assess genotoxicity in a group of wildland firefighters and evaluate the contribution of total concentration of urinary hydroxylated polycyclic aromatic hydrocarbons (ΣOHPAHs) to selected endpoints. A group of 59 northern Portuguese wildland firefighters (mean age: 35.5 ± 9.0 years) was evaluated before and during the wildfire season. Sociodemographic, lifestyle, occupational-related information was collected via questionnaire. The micronucleus (MN) assay in buccal and urothelial cells was applied to paired samples to assess the association with exposure, as indicated by urinary ΣOHPAHs levels. The risk of MN formation in urothelial cells was over twofold higher during the wildfire season [Frequency Ratio (FR): 2.13, 95 % CI: 1.99-2.27, p = 0.01]. A 35 % increase in MN frequency in buccal cells was observed during the wildfire season (FR: 1.35, 95 % CI: 0.76-2.40, p > 0.05). Urinary ΣOHPAHs exhibited a significant positive association with MN‰ in urothelial cells (FR:1.04, 95 % CI: 1.01-1.08, p < 0.05). This study provides the first assessment of MN frequency in urothelial cells of wildland firefighters, offering novel evidence of genotoxic risks and potential long-term health impacts associated with wildland firefighting.
- Minimum Information for Reporting on the Comet Assay (MIRCA): recommendations for describing comet assay procedures and resultsPublication . Møller, Peter; Azqueta, Amaya; Boutet-Robinet, Elisa; Koppen, Gudrun; Bonassi, Stefano; Milić, Mirta; Gajski, Goran; Costa, Solange; Teixeira, João Paulo; Costa Pereira, Cristiana; Dusinska, Maria; Godschalk, Roger; Brunborg, Gunnar; Gutzkow, Kristine B.; Giovannelli, Lisa; Cooke, Marcus S.; Richling, Elke; Laffon, Blanca; Valdiglesias, Vanessa; Basaran, Nursen; Del Bo’, Cristian; Zegura, Bojana; Novak, Matjaz; Stopper, Helga; Vodicka, Pavel; Vodenkova, Sona; de Andrade, Vanessa Moraes; Sramkova, Monika; Gabelova, Alena; Collins, Andrew; Langie, Sabine A.S.The comet assay is a widely used test for the detection of DNA damage and repair activity. However, there are interlaboratory differences in reported levels of baseline and induced damage in the same experimental systems. These differences may be attributed to protocol differences, although it is difficult to identify the relevant conditions because detailed comet assay procedures are not always published. Here, we present a Consensus Statement for the Minimum Information for Reporting Comet Assay (MIRCA) providing recommendations for describing comet assay conditions and results. These recommendations differentiate between 'desirable' and 'essential' information: 'essential' information refers to the precise details that are necessary to assess the quality of the experimental work, whereas 'desirable' information relates to technical issues that might be encountered when repeating the experiments. Adherence to MIRCA recommendations should ensure that comet assay results can be easily interpreted and independently verified by other researchers.
- Occupational exposure to wildland firefighting and its effects on systemic DNA damagePublication . Esteves, Filipa; Madureira, Joana; Costa, Carla; Pires, Joana; Barros, Bela; Alves, Sara; Vaz, Josiana; Oliveira, Marta; Slezakova, Klara; Fernandes, Adília; Pereira, Maria do Carmo; Morais, Simone; Valdiglesias, Vanessa; Bonassi, Stefano; Teixeira, João Paulo; Costa, SolangeBackground: Portugal is among the European Union countries more devastated by forest fires. Wildland firefighters are at the forefront of this battle, facing exposure to a wide range of harmful pollutants. Epidemiological studies have highlighted a potential link between occupational firefighting exposure and several diseases, including cancer. To date, very few studies have explored the biological mechanisms associated with such exposure. The present longitudinal study aims to assess changes in early effect biomarkers following wildland firefighters’ occupational exposure to a real wildfire event. Methods: Paired blood samples from 59 healthy Portuguese wildland firefighters were collected at two different time points: before wildfire season and after a fire event during wildfire season. Sociodemographic variables (e.g., age, sex) and work-related factors (e.g., years of service) were assessed via a self-reported questionnaire. Levels of early effect biomarkers, such as primary DNA damage and oxidative DNA damage (oxidised purines) were assessed via comet assay. DNA double-strand breaks (DSBs) were evaluated by phosphorylated H2AX (γH2AX). Moreover, hydroxylated polycyclic aromatic hydrocarbon metabolites (OHPAHs) and metal(loid)s were quantified in urine samples. The influence of urinary OHPAHs, urinary metal(loid)s, and other exposure-related factors (e.g., firefighting duration) on changes (Δ) in early effect biomarkers (post-vs. baseline levels) was investigated. Results: Firefighting activities led to a significant increase in both primary DNA damage and oxidative DNA damage by 22 % (95 % CI: 1.11–1.35; p < 0.05) and 23 % (95 % CI: 1.04–1.45; p < 0.05), respectively. Results from linear regression revealed that per each unit increase of urinary 2-hydroxyfluorene (2-OHFlu) (μmol/mol creatinine), the risk of ⧍ oxidative DNA damage increased by 20 % [FR: 1.20 (1.09–1.32); p < 0.01]. Additionally, each unit increase in urinary cesium (Cs) (μg/L) resulted in a significant 4 % increase in Δ primary DNA damage [FR: 1.04 (1.01–1.06); p < 0.05] and a 3 % increase in Δ oxidative DNA damage [FR: 1.03 (1.01–1.05); p < 0.05]. Post-exposure levels of γH2AX were significantly correlated with urinary 2-OHFlu levels assessed after firefighting (r = 0.30; p < 0.05). Furthermore, exposure duration and reported breathing difficulties during firefighting were significantly associated with increased levels of primary DNA damage. Conclusion: Results obtained provide insights into the potential human health effects of wildland firefighting occupational exposure at the genetic and molecular levels, offering new and important mechanistic data. These findings are crucial for implementing health and safety measures, recommendations, and best practices to mitigate occupational risks and protect the health of wildland firefighters.
- Occupational exposure to wildland firefighting and its effects on systemic DNA damagePublication . Esteves, Filipa; Madureira, Joana; Costa, Carla; Pires, Joana; Barros, Bela; Alves, Sara; Vaz, Josiana; Oliveira, Marta; Slezakova, Klara; Fernandes, Adília; Pereira, Maria do Carmo; Morais, Simone; Valdiglesias, Vanessa; Bonassi, Stefano; Teixeira, João Paulo; Costa, SolangeBackground: Portugal is among the European Union countries more devastated by forest fires. Wildland firefighters are at the forefront of this battle, facing exposure to a wide range of harmful pollutants. Epidemiological studies have highlighted a potential link between occupational firefighting exposure and several diseases, including cancer. To date, very few studies have explored the biological mechanisms associated with such exposure. The present longitudinal study aims to assess changes in early effect biomarkers following wildland firefighters' occupational exposure to a real wildfire event. Methods: Paired blood samples from 59 healthy Portuguese wildland firefighters were collected at two different time points: before wildfire season and after a fire event during wildfire season. Sociodemographic variables (e.g., age, sex) and work-related factors (e.g., years of service) were assessed via a self-reported questionnaire. Levels of early effect biomarkers, such as primary DNA damage and oxidative DNA damage (oxidised purines) were assessed via comet assay. DNA double-strand breaks (DSBs) were evaluated by phosphorylated H2AX (γH2AX). Moreover, hydroxylated polycyclic aromatic hydrocarbon metabolites (OHPAHs) and metal(loid)s were quantified in urine samples. The influence of urinary OHPAHs, urinary metal(loid)s, and other exposure-related factors (e.g., firefighting duration) on changes (Δ) in early effect biomarkers (post-vs. baseline levels) was investigated. Results: Firefighting activities led to a significant increase in both primary DNA damage and oxidative DNA damage by 22 % (95 % CI: 1.11-1.35; p < 0.05) and 23 % (95 % CI: 1.04-1.45; p < 0.05), respectively. Results from linear regression revealed that per each unit increase of urinary 2-hydroxyfluorene (2-OHFlu) (μmol/mol creatinine), the risk of ⧍ oxidative DNA damage increased by 20 % [FR: 1.20 (1.09-1.32); p < 0.01]. Additionally, each unit increase in urinary cesium (Cs) (μg/L) resulted in a significant 4 % increase in Δ primary DNA damage [FR: 1.04 (1.01-1.06); p < 0.05] and a 3 % increase in Δ oxidative DNA damage [FR: 1.03 (1.01-1.05); p < 0.05]. Post-exposure levels of γH2AX were significantly correlated with urinary 2-OHFlu levels assessed after firefighting (r = 0.30; p < 0.05). Furthermore, exposure duration and reported breathing difficulties during firefighting were significantly associated with increased levels of primary DNA damage. Conclusion: Results obtained provide insights into the potential human health effects of wildland firefighting occupational exposure at the genetic and molecular levels, offering new and important mechanistic data. These findings are crucial for implementing health and safety measures, recommendations, and best practices to mitigate occupational risks and protect the health of wildland firefighters.