Browsing by Author "Bonassi, Stefano"
Now showing 1 - 9 of 9
Results Per Page
Sort Options
- 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.
- 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.
- 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.
- The cytokinesis-block micronucleus (CBMN) assay in human populations exposed to styrene: a systematic review and meta-analysisPublication . Costa, Solange; Ceppi, Marcello; Costa, Carla; Silva, Susana; Pereira, Cristiana; Laffon, Blanca; Bonassi, Stefano; Teixeira, João PauloStyrene is a building-block of several compounds used in a wide array of materials and products. The most important human exposure to this substance occurs in industrial settings, especially among reinforced-plastics industry workers. The effect of occupational exposure to styrene on cytogenetics biomarkers has been previously reviewed with positive association observed for chromosomal aberrations, and inconclusive data for the micronucleus assay. Some limitations were noted in those studies, including inadequate exposure assessment and poor epidemiological design. Furthermore, in earlier studies micronuclei frequency was measured with protocols not as reliable as cytokinesis-block micronucleus (CBMN) assay. Aim of the present systematic review and meta-analysis is to investigate genomic instability and DNA damage as measured by the CBMN assay in lymphocytes of subjects exposed to styrene. A total of 11 studies published between 2004 and 2012 were included in the meta-analysis encompassing 479 styrene-exposed workers and 510 controls. The quality of each study was estimated by a quality scoring system which ranked studies according to the consideration of major confounders, exposure characterization, and technical parameters. An overall increase of micronuclei frequencies was found in styrene-exposure workers when compared to referents (meta-MR 1.34; 95% CI 1.18–1.52), with significant increases achieved in six individual studies. The consistency of results in individual studies, the independence of this result from major confounding factors and from the quality of the study strengthens the reliability of risk estimates and supports the use of the CBMN assay in monitoring genetic risk in styrene workers.
- The hCOMET project: International database comparison of results with the comet assay in human biomonitoring. Baseline frequency of DNA damage and effect of main confoundersPublication . Milić, Mirta; Ceppi, Marcello; Bruzzone, Marco; Azqueta, Amaya; Brunborg, Gunnar; Godschalk, Roger; Koppen, Gudrun; Langie, Sabine; Møller, Peter; Teixeira, João Paulo; Alija, Avdulla; Anderson, Diana; Andrade, Vanessa; Andreoli, Cristina; Asllani, Fisnik; Bangkoglu, Ezgi Eyluel; Barančoková, Magdalena; Basaran, Nursen; Boutet-Robinet, Elisa; Buschini, Annamaria; Cavallo, Delia; Costa Pereira, Cristiana; Costa, Carla; Costa, Solange; Da Silva, Juliana; Del Boˊ, Cristian; Dimitrijević Srećković, Vesna; Djelić, Ninoslav; Dobrzyńska, Malgorzata; Duračková, Zdenka; Dvořáková, Monika; Gajski, Goran; Galati, Serena; García Lima, Omar; Giovannelli, Lisa; Goroshinskaya, Irina A.; Grindel, Annemarie; Gutzkow, Kristine B.; Hernández, Alba; Hernández, Carlos; Holven, Kirsten B.; Ibero-Baraibar, Idoia; Ottestad, Inger; Kadioglu, Ela; Kažimirová, Alena; Kuznetsova, Elena; Ladeira, Carina; Laffon, Blanca; Lamonaca, Palma; Lebailly, Pierre; Louro, Henriqueta; Mandina Cardoso, Tania; Marcon, Francesca; Marcos, Ricard; Moretti, Massimo; Moretti, Silvia; Najafzadeh, Mojgan; Nemeth, Zsuzsanna; Neri, Monica; Novotna, Bozena; Orlow, Irene; Paduchova, Zuzana; Pastor, Susana; Perdry, Hervé; Spremo-Potparević, Biljana; Ramadhani, Dwi; Riso, Patrizia; Rohr, Paula; Rojas, Emilio; Rossner, Pavel; Safar, Anna; Sardas, Semra; Silva, Maria João; Sirota, Nikolay; Smolkova, Bozena; Staruchova, Marta; Stetina, Rudolf; Stopper, Helga; Surikova, Ekaterina I.; Ulven, Stine M.; Ursini, Cinzia Lucia; Valdiglesias, Vanessa; Valverde, Mahara; Vodicka, Pavel; Volkovova, Katarina; Wagner, Karl-Heinz; Živković, Lada; Dušinská, Maria; Collins, Andrew R.; Bonassi, StefanoThe alkaline comet assay, or single cell gel electrophoresis, is one of the most popular methods for assessing DNA damage in human population. One of the open issues concerning this assay is the identification of those factors that can explain the large inter-individual and inter-laboratory variation. International collaborative initiatives such as the hCOMET project - a COST Action launched in 2016 - represent a valuable tool to meet this challenge. The aims of hCOMET were to establish reference values for the level of DNA damage in humans, to investigate the effect of host factors, lifestyle and exposure to genotoxic agents, and to compare different sources of assay variability. A database of 19,320 subjects was generated, pooling data from 105 studies run by 44 laboratories in 26 countries between 1999 and 2019. A mixed random effect log-linear model, in parallel with a classic meta-analysis, was applied to take into account the extensive heterogeneity of data, due to descriptor, specimen and protocol variability. As a result of this analysis interquartile intervals of DNA strand breaks (which includes alkali-labile sites) were reported for tail intensity, tail length, and tail moment (comet assay descriptors). A small variation by age was reported in some datasets, suggesting higher DNA damage in oldest age-classes, while no effect could be shown for sex or smoking habit, although the lack of data on heavy smokers has still to be considered. Finally, highly significant differences in DNA damage were found for most exposures investigated in specific studies. In conclusion, these data, which confirm that DNA damage measured by the comet assay is an excellent biomarker of exposure in several conditions, may contribute to improving the quality of study design and to the standardization of results of the comet assay in human populations.
- The impact of indoor air quality and contaminants on respiratory health of older people living in long-term care residences in PortoPublication . Mendes, Ana; Papoila, Ana Luísa; Carreiro-Martins, Pedro; Bonassi, Stefano; Caires, Iolanda; Palmeiro, Teresa; Aguiar, Lívia; Pereira, Cristiana; Neves, Paula; Mendes, Diana; Botelho, Maria Amália Silveira; Neuparth, Nuno; Teixeira, João PauloBackground: persons who are 65 years or older often spend an important part of their lives indoors thus adverse indoor climate might influence their health status. Objective: to evaluate the influence of indoor air quality and contaminants on older people’s respiratory health. Design: cross-sectional study. Setting: 21 long-term care residences (LTC) in the city of Porto, Portugal. Subjects: older people living in LTC with ≥65 years old. Methods: the Portuguese version of BOLD questionnaire was administered by an interviewer to older residents able to participate (n = 143). Indoor air contaminants (IAC) were measured twice, during winter and summer in 135 areas. Mixed effects logistic regression models were used to study the association between the health questionnaire results and the monitored IAC, adjusted for age, smoking habits, gender and number of years living in the LTC. Results: cough (23%) and sputum (12%) were the major respiratory symptoms, and allergic rhinitis (18%) the main selfreported illness. Overall particulate matter up to 2.5 micrometres in size median concentration was above the reference levels both in winter and summer seasons. Peak values of particulate matter up to 10 micrometres in size (PM10), total volatile organic compounds, carbon dioxide, bacteria and fungi exceeded the reference levels. Older people exposed to PM10 above the reference levels demonstrated higher odds of allergic rhinitis (OR = 2.9, 95% CI: 1.1–7.2). Conclusion: high levels of PM10 were associated with 3-fold odds of allergic rhinitis. No association was found between indoor air chemical and biological contaminants and respiratory symptoms.