1,720,976 research outputs found
Renal transcriptome-wide analyses in association with kidney black carbon load
No full textRationale and objectiveInhaled black carbon (BC) has been previously shown to reach and accumulate in the kidneys. As kidneys filter toxicants, they may be susceptible to adverse effects caused by BC accumulation. We studied gene expressions and pathways related to BC particle load in kidney biopsy tissue.Study designGene expression was measured in 29 kidney biopsies performed at one or two years post-transplantation using Affymetrix microarray. We performed a transcriptome-wide association analysis using linear regression analyses, adjusting for individual characteristics to investigate alterations in gene expression in association with kidney BC. Finally, we performed overrepresentation analyses (ConsensusPathDB) to identify enriched pathways and gene ontology sets.ResultsThe geometric mean (5th, 95th percentile) of BC particle levels was 5.4 x 103 (1.5 x 103, 4.1 x 104) number of BC particles per mm(3) kidney tissue. The BC particle load associated with gene expression in overrepresenting pathways related to ciliopathies, macrophage-derived proteins involved in anti-inflammatory response, DNA damage response, TP53 regulation, and necrosis. We identified BC associated genes involved in GO terms ciliogenesis and ciliary structure, including genes involved in the ciliary plasm and axoneme. Furthermore, we found significantly BC-associated genes involved in RNA-related processes, including e.g., genes in the integrator complex.ConclusionsHere, we identified genes and pathways associated with real-life kidney BC particle load, indicating alterations in gene expression involved in assembly and maintenance of primary cilia, the anti-inflammatory properties of the innate immune system, and DNA damage-related pathways. These findings highlight the need for public health measures to reduce exposure and protect kidney health in at-risk populations.Funding
LR acknowledges funding from the Special Research Fund (Special Research Fund, BOF) for a doctoral fellowship: BOF20DOC15. The BC work is supported by a Methusalem grant from TSN. The Research Foundation Flanders (FWO) funds JC (1196119 N) and MN (1844019 N). Additionally, MN is supported by an ERAcoSysMed H2020 grant (JTC2_29), and a C3 internal grant from the KU Leuven (C32/17/049). None of the funding agencies had a role in the design and conduct of the study, in the collection, analysis and interpretation of the data, or in the preparation, review, or approval of the manuscript.
Acknowledgements
The authors want to express their greatest gratitude to the kidney transplant patients, as well as the staff of the department of Nephrology at the University Hospitals Leuven
Impact on murine neurodevelopment of early-life exposure to airborne ultrafine carbon nanoparticles
No full textThe effects of ultrafine particle (UFP) inhalation on neurodevelopment, especially during critical windows of early life, remain largely unexplored. The specific time windows during which exposure to UFP might be the most detrimental remain poorly understood. Here, we studied early-life exposure to clean ultrafine carbonaceous particles (UFPC) and neurodevelopment and central nervous system function in offspring.Pregnant wild-type C57BL/6J mice were either sham-exposed (HEPA-filtered air) or exposed to clean ultrafine carbonaceous particles at a concentration of 438 ± 72 μg/m³ (mean ± SD) and a count median diameter of 49 ± 2 nm (CMD ± GSD) via whole-body exposure for four hours per day. For prenatal exposure, mice were exposed for two consecutive days in two exposure periods, while the postnatal exposure was conducted for four consecutive days in two exposure periods. The mice were divided into four groups: (i) sham, (ii) only prenatal exposure, (iii) only postnatal exposure, and (iv) both prenatal and postnatal exposure. Neurodevelopmental behaviour was assessed throughout the life of the offspring using a functional observation battery.Early-life UFPC-exposed offspring exhibited altered anxiety-related behaviour in the open field test, with exclusively postnatally exposed offspring (567 ± 120 s) spending significantly more time within the border zone of the arena compared to the sham group (402 ± 73 s), corresponding to an increase of approximately 41% (p < 0.05). The behavioural alterations remained unaffected by olfactory function or maternal behaviour. Mice with both prenatal and postnatal exposure did not show this effect. No discernible impact on developmental behavioural reflexes was evident.Early life exposure to UFPC, particularly during the early postnatal period, may lead to developmental neurotoxicity, potentially resulting in complications for the central nervous system later in life. The current data will support future studies investigating the possible effects and characteristics of nanoparticle-based toxicity.Funding
This work was funded by the Flemish Scientific Research Foundation (FWO; G059219) and supported by the European Union’s Horizon 2020 research and innovation programme under grant agreement No 814978 (TUBE).
Acknowledgements
We would like to thank the National Institute for Public Health and the Environment (RIVM) technical staff for their significant contributions to this study. We express our special gratitude to Evert Duistermaat, Paul Fokkens,
and John Boere for their dedicated efforts in setting up the exposure experiments to ultrafine particles (UFPC). Their meticulous work in carrying out the exposures and processing the subsequent exposure data was crucial
to this study’s accomplishment. Without their expertise, this study would not have been possible. This work was funded by the Flemish Scientific Research Foundation (FWO; G059219) and supported by the European Union’s Horizon 2020 research and innovation programme under grant agreement No 814978 (TUBE)
Newborn glomerular function and gestational particulate air pollution
No full textBackground Nephron number variability may hold significance in the Developmental Origins of Health and Disease hypothesis. We explore the impact of gestational particulate pollution exposure on cord blood cystatin C, a marker for glomerular function, as an indicator for glomerular health at birth. Methods From February 2010 onwards, the ENVIRONAGE cohort includes over 2200 mothers giving birth at the East-Limburg hospital in Genk, Belgium. Mothers without planned caesarean section who are able to fill out a Dutch questionnaire are eligible. Here, we evaluated cord blood cystatin C levels from 1484 mother-child pairs participating in the ENVIRONAGE cohort. We employed multiple linear regression models and distributed lag models to assess the association between cord blood cystatin C and gestational particulate air pollution exposure. Findings Average +/- SD levels of cord blood cystatin C levels amounted to 2.16 +/- 0.35 mg/L. Adjusting for covariates, every 0.5 mu g/m(3) and 5 mu g/m(3) increment in gestational exposure to black carbon (BC) and fine particulate matter (PM2.5) corresponded to increases of 0.04 mg/L (95% CI 0.01-0.07) and 0.07 mg/L (95% CI 0.03-0.11) in cord blood cystatin C levels (p < 0.01), respectively. Third-trimester exposure showed similar associations, with a 0.04 mg/L (95% CI 0.00-0.08) and 0.06 mg/L (95% CI 0.04-0.09) increase for BC and PM2.5 (p < 0.02). No significant associations were observed when considering only the first and second trimester exposure. Interpretation Our findings indicate that particulate air pollution during the entire pregnancy, with the strongest effect sizes from week 27 onwards, may affect newborn kidney function, with potential long-term implications for later health.Funding
Special Research Fund (Bijzonder Onderzoeksfonds, BOF), Flemish Scientific Research Fund (Fonds Wetenschappelijk Onderzoek, FWO), and Methusalem
Acknowledgements
This ENVIRONAGE birth cohort study is supported Methusalum grant and the Flemish Scientific Research Fund (FWO, N1516112/ G087311N10). LR acknowledges funding from the Special Research Fund (Bijzonder Onderzoeksfonds, BOF) for a doctoral fellowship (BOF20DOC15). The authors want to express their greatest gratitude to the participating parents and children, as well as the staff of the maternity ward, the midwives, and the staff of the clinical laboratory of the East-Limburg Hospital in Genk
Cord Blood Proteomic Profiles, Birth Weight, and Early Life Growth Trajectories
No full textImportance The cord blood proteome, a repository of proteins derived from both mother and fetus, might offer valuable insights into the physiological and pathological state of the fetus. However, its association with birth weight and growth trajectories early in life remains unexplored.
Objective To identify cord blood proteins associated with birth weight and the birth weight ratio (BWR) and to evaluate the associations of these cord blood proteins with early growth trajectories.
Design, Setting, and Participants This cohort study included 288 mother-child pairs from the ongoing prospective Environmental Influence on Early Aging birth cohort study. Newborns were recruited from East-Limburg Hospital in Genk, Belgium, between February 2010 and November 2017 and followed up until ages 4 to 6 years. Data were analyzed from February 2022 to September 2023.
Main Outcomes and Measures The outcome of interest was the associations of 368 inflammatory-related cord blood proteins with birth weight or BWR and with early life growth trajectories (ie, rapid growth at age 12 months and weight, body mass index [BMI] z score, waist circumference, and overweight at age 4-6 years) using multiple linear regression models. The BWR was calculated by dividing the birth weight by the median birth weight of the population-specific reference growth curve, considering parity, sex, and gestational age. Results are presented as estimates or odds ratios (ORs) for each doubling in proteins.
Results The sample included 288 infants (125 [43.4%] male; mean [SD] gestation age, 277.2 [11.6] days). The mean (SD) age of the child at the follow-up examination was 4.6 (0.4) years old. After multiple testing correction, there were significant associations of birth weight and BWR with 7 proteins: 2 positive associations: afamin (birth weight: coefficient, 341.16 [95% CI, 192.76 to 489.50]) and secreted frizzled-related protein 4 (SFRP4; birth weight: coefficient, 242.60 [95% CI, 142.77 to 342.43]; BWR: coefficient, 0.07 [95% CI, 0.04 to 0.10]) and 5 negative associations: cadherin EGF LAG 7-pass G-type receptor 2 (CELSR2; birth weight: coefficient, −237.52 [95% CI, −343.15 to −131.89]), ephrin type-A receptor 4 (EPHA4; birth weight: coefficient, −342.78 [95% CI, −463.10 to −222.47]; BWR: coefficient, −0.11 [95% CI, −0.14 to −0.07]), SLIT and NTRK-like protein 1 (SLITRK1; birth weight: coefficient, −366.32 [95% CI, −476.66 to −255.97]; BWR: coefficient, −0.11 [95% CI, −0.15 to −0.08]), transcobalamin-1 (TCN1; birth weight: coefficient, −208.75 [95% CI, −305.23 to −112.26]), and unc-5 netrin receptor D (UNC5D; birth weight: coefficient, −209.27 [95% CI, −295.14 to −123.40]; BWR: coefficient, −0.07 [95% CI, −0.09 to −0.04]). Further evaluation showed that 2 proteins were still associated with rapid growth at age 12 months (afamin: OR, 0.32 [95% CI, 0.11-0.88]; TCN1: OR, 2.44 [95% CI, 1.26-4.80]). At age 4 to 6 years, CELSR2, EPHA4, SLITRK1, and UNC5D were negatively associated with weight (coefficients, −1.33 to −0.68 kg) and body mass index z score (coefficients, −0.41 to −0.23), and EPHA4, SLITRK1, and UNC5D were negatively associated with waist circumference (coefficients, −1.98 to −0.87 cm). At ages 4 to 6 years, afamin (OR, 0.19 [95% CI, 0.05-0.70]) and SLITRK1 (OR, 0.32 [95% CI, 0.10-0.99]) were associated with lower odds for overweight.
Conclusions and Relevance This cohort study found 7 cord blood proteins associated with birth weight and growth trajectories early in life. Overall, these findings suggest that stressors that could affect the cord blood proteome during pregnancy might have long-lasting associations with weight and body anthropometrics
Air pollution exposure and bone mineral density in young children: results from the ENVIRONAGE birth cohort
No full textPrevious epidemiological studies have suggested that air pollution exposure has an adverse effect on bone health in older individuals. However , no studies on early life exposure to air pollution and childhood bone mineral density have been reported. Therefore, this study aims to investigate whether long-term exposure to air pollution is associated with a change in bone mineral density in young children. Within the ongoing prospective birth cohort ENVIRONAGE (Envi-ronmental Influence on Ageing in Early Life), a total of 478 children aged 4-6 were followed-up. Radial bone mineral density (m/s) was assessed using a quantitative ultrasound method. The residential air pollution exposure (μg/m 3) one year before the follow-up was estimated using a high-resolution spatial-temporal interpolation method. Multiple linear regression models were used after adjusting for relevant covariates and potential confounders. Radial bone mineral density was on average (SD) 3680.84 (112.39) m/s. An interquartile (IQR) increment in long-term exposure to PM 2.5 (2.54 μg/m 3) and PM 10 (3.65 μg/m 3) was associated with a decrease of 24.81 m/s (95% CI:-42.55% to-7.07%, p=0.006) and 26.24 m/s (95% CI:-41.95% to 10.54%, p=0.001) in bone mineral density, respectively. On the other hand, no significant associations were observed for long-term exposure to nitrogen dioxide and black carbon. These findings provide evidence that long-term exposure to particulate matter has a relevant effect on childhood bone mineral density. Moreover, this study reinforces the need for increased public health policies and awareness campaigns on air quality improvement with long-term implications on bone health.Flemish Scientific Fund [G073315N/G048420N/G026222P]; European Unio
Air pollution exposure and bone mineral density in young children: results from the ENVIRONAGE birth cohort
No full textPrevious epidemiological studies have suggested that air pollution exposure has an adverse effect on bone health in older individuals. However , no studies on early life exposure to air pollution and childhood bone mineral density have been reported. Therefore, this study aims to investigate whether long-term exposure to air pollution is associated with a change in bone mineral density in young children. Within the ongoing prospective birth cohort ENVIRONAGE (Envi-ronmental Influence on Ageing in Early Life), a total of 478 children aged 4-6 were followed-up. Radial bone mineral density (m/s) was assessed using a quantitative ultrasound method. The residential air pollution exposure (μg/m 3) one year before the follow-up was estimated using a high-resolution spatial-temporal interpolation method. Multiple linear regression models were used after adjusting for relevant covariates and potential confounders. Radial bone mineral density was on average (SD) 3680.84 (112.39) m/s. An interquartile (IQR) increment in long-term exposure to PM 2.5 (2.54 μg/m 3) and PM 10 (3.65 μg/m 3) was associated with a decrease of 24.81 m/s (95% CI:-42.55% to-7.07%, p=0.006) and 26.24 m/s (95% CI:-41.95% to 10.54%, p=0.001) in bone mineral density, respectively. On the other hand, no significant associations were observed for long-term exposure to nitrogen dioxide and black carbon. These findings provide evidence that long-term exposure to particulate matter has a relevant effect on childhood bone mineral density. Moreover, this study reinforces the need for increased public health policies and awareness campaigns on air quality improvement with long-term implications on bone health.Flemish Scientific Fund [G073315N/G048420N/G026222P]; European Unio
Lupus, DNA Methylation, and Air Pollution: A Malicious Triad
No full textThe pathogenesis of systemic lupus erythematosus (SLE) remains elusive to this day; however, genetic, epigenetic, and environmental factors have been implicated to be involved in disease pathogenesis. Recently, it was demonstrated that in systemic lupus erythematosus (SLE) patients, interferon-regulated genes are hypomethylated in naïve CD4+ T cells, CD19+ B lymphocytes, and CD14+ monocytes. This suggests that interferon-regulated genes may have been epigenetically poised in SLE patients for rapid expression upon stimulation by different environmental factors. Additionally, environmental studies have identified DNA (hypo)methylation changes as a potential mechanism of environmentally induced health effects in utero, during childhood and in adults. Finally, epidemiologic studies have firmly established air pollution as a crucial SLE risk factor, as studies showed an association between fine particulate matter (PM2.5) and traditional SLE biomarkers related to disease flare, hospital admissions, and an increased SLEDAI score. In this review, the relationship between aberrant epigenetic regulation, the environment, and the development of SLE will be discussed
Associations between urinary paraben concentrations and measures of cardiometabolic risk in pre-school children of the ENVIRONAGE birth cohort
No full textBackground and Aim: Parabens are widely used as antimicrobial preservatives in personal care products. Endocrine-disrupting effects have been described previously, but studies investigating obesogenic or cardiovascular effects have shown discordant results. Cardiometabolic changes associated with paraben exposure and predictive for later life health conditions may already be visible in early life. Methods: Paraben concentrations [methyl (MeP), ethyl (EtP), propyl (PrP), and butyl (BuP)] were measured by ultra-performance liquid chromatography/tandem mass spectrometry in 300 urinary samples from 4-6-year-old children of the ENVIRONAGE birth cohort. Values below the limit of quantification (LOQ) were imputed by censored likelihood multiple imputations. The association with anthropometric and cardiovascular measurements (BMI z-scores, waist circumference, blood pressure and retinal microvasculature) was analyzed in multiple linear regression models with a priori selected covariates. Effect modification by sex was investigated by including interaction terms. Results: The geometric means (geometric SD) of urinary MeP, EtP, and PrP levels above the (LOQ) were 32.60 (6.64), 1.26 (3.50), and 4.82 (4.11) µg/L respectively. For BuP 97% of all measurements were below the LOQ. In adjusted models with log-transformed paraben values MeP was associated with central retinal venular equivalent (β = 1.33, p = 0.029) and inversely associated with BMI z-scores (β =-0.065, p = 0.019). PrP was associated with the retinal tortuosity index (β = 0.0018, p = 0.0034). Additionally, EtP was significantly associated with BMI z-scores in boys (β = 0.12, p = 0.012). Conclusions: The inverse association between MeP and BMI z-scores could illustrate underlying biological mechanisms related to endocrine-disrupting properties of parabens. Associations between parabens and retinal microvasculature in preschool children may indicate adverse effects on cardiometabolic health even at a young age and provide a starting point for further research on paraben-related modes of action
Association of Newborn Telomere Length With Blood Pressure in Childhood
No full textIMPORTANCE: Adult telomere length (TL) is a biological marker of aging associated with vascular health. TL at birth is associated with later life TL and may contain early biological information of later life cardiovascular health and disease. OBJECTIVE: To evaluate whether newborn TL is associated with early life blood pressure differences in childhood. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was part of the ENVIRONAGE (Environmental Influence on Aging in Early Life) study, a birth cohort of Belgian mother-child pairs with recruitment at birth and a median follow-up of 4.5 years conducted between October 2014 and July 2021. Participants included for analysis provided full data for evaluation at follow-up visit. Data analysis was conducted between August and September 2021. MAIN OUTCOMES AND MEASURES: Cord blood and placental average relative TL were measured at birth using quantitative polymerase chain reaction (qPCR). Systolic, diastolic, and mean arterial pressure (MAP) were evaluated at follow-up. High childhood blood pressure (standardized for child age, sex, and height) was defined following the 2017 American Academy of Pediatrics guidelines. Multivariable adjusted linear and logistic regression models were used to associate newborn TL and blood pressure indicators in childhood. RESULTS: This study included 485 newborn children (52.8% girls) with a mean (SD) age of 4.6 (0.4) years at the follow-up visit. Newborn TL was associated with lower blood pressure in childhood. A 1-IQR increase in cord blood TL was associated with a –1.54 mm Hg (95% CI, –2.36 to –0.72 mm Hg) lower diastolic blood pressure and –1.18 mm Hg (95% CI, –1.89 to –0.46 mm Hg) lower MAP. No association was observed with systolic blood pressure. Furthermore, a 1-IQR increase in cord blood TL was associated with lower odds of having high blood pressure at the age of 4 to 6 years (adjusted OR, 0.72; 95% CI, 0.53 to 0.98). In placenta, a 1-IQR increase in TL was associated with a –0.96 mm Hg (95% CI, –1.72 to –0.21 mm Hg) lower diastolic, –0.88 mm Hg (95% CI, –1.54 to –0.22 mm Hg) lower MAP, and a lower adjusted OR of 0.69 (95% CI, 0.52 to 0.92) for having a high blood pressure in childhood. CONCLUSIONS AND RELEVANCE: In this prospective birth cohort study, variation in early life blood pressure at school-age was associated with TL at birth. Cardiovascular health may to some extent be programmed at birth, and these results suggest that TL entails a biological mechanism in this programming
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