Search Results (15)

LC continues to be the leading cause of cancer mortality globally, among both males and females, representing a major public health challenge. The impact of mitochondria on human health and disease is a rapidly growing focus in scientific research, due to their critical roles in cellular survival and death. Mitochondria play an important role in controlling imperative cellular parameters, and alterations in mtDNAcn might be crucial for LC development. MtDNAcn has been studied as a possible marker for LC risk, but its role in prevention is still unclear. This review and meta-analysis aims to summarize the current evidence and provide an overall estimate of the relationship between the mtDNA copy number in human samples like blood and sputum. PubMed, Web of Science, and Scopus databases were used for studies published up to February 2024, following PRISMA and MOOSE guidelines. Studies were combined using a random-effects model, and we assessed the heterogeneity between studies with the chi-square-based Cochran’s Q statistic and the I² statistic. Publication bias was checked using Begg’s and Egger’s tests. Five studies, including a total of 3.748 participants, met the eligibility criteria. The MtDNA copy number was measured in blood or sputum samples and compared across different quantiles. The pooled analysis did not find a significant association between the mtDNA copy number and LC risk (OR = 0.94; 95% CI: 0.49–1.78). Moreover, when looking at different study designs, no significant results were found, due to the small number of studies available. No significant publication bias was detected. Further studies are needed to better understand the connection between the mtDNA copy number and LC risk and to better understand the role of potential confounders. Full article

Background: Lung cancer (LC) is the leading cause of cancer deaths worldwide among both men and women, and represents a major public health challenge. DNA methylation (DNAm) has shown potential in identifying individuals at higher risk of LC, but the overall evidence has not been systematically evaluated. This review and meta-analysis aims to evaluate and summarize existing research on the association between blood DNAm levels and LC risk. Methods: Searches were conducted in PubMed, Web of Science, and Scopus for studies published until February 2024, following PRISMA and MOOSE guidelines. Eleven studies met the eligibility criteria. Results: Using a random effects model, our pooled analysis showed a significant association between increased DNAm levels and LC risk (OR 1.24, 95% CI 1.10–1.39; I² = 93.90%, p = 0.0001). Stratifying the results by study design showed a stronger association in two prospective cohort studies (OR 1.61; 95% CI 1.36–1.90; I² = 14.42%, p = 0.32), while case–control studies showed a weaker association (OR 1.05; 95% CI 0.99–1.11; I² = 70.57%, p = 0.0001). Sensitivity analyses indicated that omitting individual studies did not significantly alter the LC risk estimates. Conclusions: These findings suggest that higher blood DNAm levels are associated with an increased risk of LC, especially in long-term cohort studies. Further research is recommended to explore the potential of DNAm as a screening biomarker for LC and to clarify the role of other influencing factors. Full article

Latinas experience physical and psychological stressors in pregnancy leading to increased morbidity and higher risk for adverse birth outcomes. Epigenetic changes, including DNA methylation (DNAm), have been proposed as markers to create more refined risk stratification, yet few of these studies have examined these changes in Latinas. We conducted a secondary analysis of stored blood leukocytes of Latina women (n = 58) enrolled in a larger National Institutes of Health funded R01 project (2011–2016). We examined DNAm on eight candidate stress genes to compare physically and psychologically stressed participants to healthy (low stress) participants. We found unique CpGs that were differentially methylated in stressed women early- and mid-pregnancy compared to the healthy group, though none remained significant after FDR correction. Both physical and psychological stress were associated with hypomethylation at two consecutive CpG sites on NR3C1 in early pregnancy and one CpG site on NR3C1 in mid-pregnancy before adjustment. Stress was also associated with hypomethylation at two CpG sites on FKBP5 in early and mid-pregnancy but were no longer significant after FDR adjustment. Though we did not find statistically significant differences in DNAm during pregnancy between stressed and healthy women in this sample, signals were consistent with previous findings. Future work in larger samples should further examine the associations between stress and DNAm in pregnancy as this mechanism may explain underlying perinatal health inequities. Full article

Pregnant individuals are exposed to acetaminophen and caffeine, but it is unknown how these exposures interact with the developing gut microbiome. We aimed to determine whether acetaminophen and/or caffeine relate to the childhood gut microbiome and whether features of the gut microbiome alter the relationship between acetaminophen/caffeine and neurodevelopment. Forty-nine and 85 participants provided meconium and stool samples at 6–7, respectively, for exposure and microbiome assessment. Fecal acetaminophen and caffeine concentrations were quantified, and fecal DNA underwent metagenomic sequencing. Caregivers and study staff assessed the participants’ motor and cognitive development using standardized scales. Prenatal exposures had stronger associations with the childhood microbiome than concurrent exposures. Prenatal acetaminophen exposure was associated with a trend of lower gut bacterial diversity in childhood [β = −0.17 Shannon Index, 95% CI: (−0.31, −0.04)] and was marginally associated with differences in the relative abundances of features of the gut microbiome at the phylum (Firmicutes, Actinobacteria) and gene pathway levels. Among the participants with a higher relative abundance of Proteobacteria, prenatal exposure to acetaminophen and caffeine was associated with lower scores on WISC-IV subscales. Acetaminophen during bacterial colonization of the naïve gut is associated with lasting alterations in childhood microbiome composition. Future studies may inform our understanding of downstream health effects. Full article

Advocating for healthy environments is a matter of justice. Changes in environments have tremendous impacts on the health of communities, and oftentimes, individuals are unable to safeguard themselves through individual actions alone. Efforts frequently require collective action and are often most effective when led by the communities most impacted. In this spirit, we launched “Vibrations”, an African environment photo essay contest. Through funding and publicity, we aimed to support community-led environmental improvement and education initiatives presently taking place on the continent. We received nearly two dozen submissions and selected eight winners. The winners come from five countries (Ghana, Kenya, Mozambique, Nigeria, and South Africa) and have taken on a range of projects aimed at improving environments across a variety of African regions. Projects included efforts to combat pollution, create environmentally conscious school curricula, utilize clean energy sources, and spread awareness about environmental justice concerns in local communities. It is our hope that this report highlights these transformative community-driven efforts, promotes continued conversations on environmental justice in Africa, and encourages meaningful action via policy changes and collaborations throughout the African continent and beyond. Full article

An altered mitochondrial DNA copy number (mtDNAcn) at birth can be a marker of increased disease susceptibility later in life. Gestational exposure to acute stress, such as that derived from the earthquake experienced on 19 September 2017 in Mexico City, could be associated with changes in mtDNAcn at birth. Our study used data from the OBESO (Biochemical and Epigenetic Origins of Overweight and Obesity) perinatal cohort in Mexico City. We compared the mtDNAcn in the umbilical cord blood of 22 infants born before the earthquake, 24 infants whose mothers were pregnant at the time of the earthquake (exposed), and 37 who were conceived after the earthquake (post-earthquake). We quantified mtDNAcn by quantitative real-time polymerase chain reaction normalized with a nuclear gene. We used a linear model adjusted by maternal age, body mass index, socioeconomic status, perceived stress, and pregnancy comorbidities. Compared to non-exposed newborns (mean ± SD mtDNAcn: 0.740 ± 0.161), exposed and post-earthquake newborns (mtDNAcn: 0.899 ± 0.156 and 0.995 ± 0.169, respectively) had increased mtDNAcn, p = 0.001. The findings of this study point at mtDNAcn as a potential biological marker of acute stress and suggest that experiencing an earthquake during pregnancy or before gestation can have programing effects in the unborn child. Long-term follow-up of newborns to women who experience stress prenatally, particularly that derived from a natural disaster, is warranted. Full article

Animal studies have shown that developmental exposures to polybrominated diphenyl ethers (PBDE) permanently affect blood/liver balance of lipids. No human study has evaluated associations between in utero exposures to persistent organic pollutants (POPs) and later life lipid metabolism. In this pilot, maternal plasma levels of PBDEs (BDE-47, BDE-99, BDE-100, and BDE-153) and polychlorinated biphenyls (PCB-138, PCB-153, and PCB-180) were determined at delivery in participants of GESTation and Environment (GESTE) cohort. Total cholesterol (TCh), triglycerides (TG), low- and high-density lipoproteins (LDL-C and HDL-C), total lipids (TL), and PBDEs were determined in serum of 147 children at ages 6–7. General linear regression was used to estimate the relationship between maternal POPs and child lipid levels with adjustment for potential confounders, and adjustment for childhood POPs. In utero BDE-99 was associated with lower childhood levels of TG (p = 0.003), and non-significantly with HDL-C (p = 0.06) and TL (p = 0.07). Maternal PCB-138 was associated with lower childhood levels of TG (p = 0.04), LDL-C (p = 0.04), and TL (p = 0.02). Our data indicate that in utero exposures to POPs may be associated with long lasting decrease in circulating lipids in children, suggesting increased lipid accumulation in the liver, a mechanism involved in NAFLD development, consistent with previously reported animal data. Full article

Exposure to metals including lead (Pb), cadmium (Cd), and arsenic (As), may impair kidney function as individual toxicants or in mixtures. However, no single medium is ideal to study multiple metals simultaneously. We hypothesized that multi-media biomarkers (MMBs), integrated indices combining information across biomarkers, are informative of adverse kidney function. Levels of Pb, Cd, and As were quantified in blood and urine in 4–6-year-old Mexican children (n = 300) in the PROGRESS longitudinal cohort study. We estimated the mixture effects of these metals, using weighted quantile sum regression (WQS) applied to urine biomarkers (Umix), blood biomarkers (Bmix), and MMBs, on the cystatin C-based estimated glomerular filtration rate (eGFR) and serum cystatin C assessed at 8–10 years of age, adjusted for covariates. Quartile increases in Umix and the MMB mixture were associated with 2.5% (95%CI: 0.1, 5.0) and 3.0% (95%CI: 0.2, 5.7) increased eGFR and −2.6% (95% CI: −5.1%, −0.1%) and −3.3% (95% CI: −6.5%, −0.1%) decreased cystatin C, respectively. Weights indicate that the strongest contributors to the associations with eGFR and serum cystatin C were Cd and Pb, respectively. MMBs detected mixture effects distinct from associations with individual metals or media-type, highlighting the benefits of incorporating information from multiple exposure media in mixtures analyses. Full article

Pregnancy is a contributor to the obesity epidemic in women, probably through postpartum weight retention (PPWR), weight gain (PPWG), or a combination of both (PPWR + WG). The contribution of these patterns of postpartum weight change to long-term maternal health remains understudied. In a secondary analysis of 361 women from the prospective cohort PROGRESS, we evaluated the associations between patterns of weight change one year after delivery and cardiometabolic risk factors at six years postpartum. Using principal component analysis, we grouped cardiometabolic risk factors into: (1) body mass index (BMI), waist circumference (WC), homeostatic model assessment of insulin resistance (HOMA-IR), high-density lipoprotein cholesterol (HDL-c), triglycerides (TG), and glucose; (2) systolic (SBP) and diastolic blood pressure (DBP); and (3) low-density lipoprotein cholesterol and total cholesterol. Using path analysis, we studied direct (patterns of weight change-outcomes) and indirect associations through BMI at six years postpartum. Around 60% of women returned to their pregestational weight (reference) by one year postpartum, 6.6% experienced PPWR, 13.9% PPWG, and 19.9% PPWR + WG. Women with PPWR + WG, vs. the reference, had higher BMI and WC at six years (2.30 kg/m², 95% CI [1.67, 2.93]; 3.38 cm [1.14, 5.62]). This was also observed in women with PPWR (1.80 kg/m² [0.80, 2.79]; 3.15 cm [−0.35, 6.65]) and PPWG (1.22 kg/m² [0.53, 1.92]; 3.32 cm [0.85, 5.78]). PPWR + WG had a direct association with HOMA-IR (0.21 units [0.04, 0.39]). The three patterns of weight change, vs. the reference, had significant indirect associations with HOMA-IR, glucose, TG, HDL-c, SBP, and DBP through BMI at six years. In conclusion, women with PPWR + WG are at high-risk for obesity and insulin resistance. Interventions targeting women during pregnancy and the first year postpartum may have implications for their long-term risk of obesity and cardiovascular disease. Full article

Essential hypertension is the leading preventable cause of death in the world. Epidemiological studies have shown that physical training can reduce blood pressure (BP), both in hypertensive and healthy individuals. Increasing evidence is emerging that DNA methylation is involved in alteration of the phenotype and of vascular function in response to environmental stimuli. We evaluated repetitive element and gene-specific DNA methylation in peripheral blood leukocytes of 68 volunteers, taken before (T0) and after (T1) a three-month intervention protocol of continuative aerobic physical exercise. DNA methylation was assessed by bisulfite-PCR and pyrosequencing. Comparing T0 and T1 measurements, we found an increase in oxygen consumption at peak of exercise (VO_2peak) and a decrease in diastolic BP at rest. Exercise increased the levels of ALU and Long Interspersed Nuclear Element 1 (LINE-1) repetitive elements methylation, and of Endothelin-1 (EDN1), Inducible Nitric Oxide Synthase (NOS2), and Tumour Necrosis Factor Alpha (TNF) gene-specific methylation. VO_2peak was positively associated with methylation of ALU, EDN1, NOS2, and TNF; systolic BP at rest was inversely associated with LINE-1, EDN1, and NOS2 methylation; diastolic BP was inversely associated with EDN1 and NOS2 methylation. Our findings suggest a possible role of DNA methylation for lowering systemic BP induced by the continuative aerobic physical training program. Full article

DNA methylation may play a critical role in aging and age-related diseases. DNA methylation phenotypic age (DNAmPhenoAge) is a new aging biomarker and predictor of chronic disease risk. While smoking is a strong risk factor for chronic diseases and influences methylation, its influence on DNAmPhenoAge is unknown. We investigated associations of self-reported and epigenetic smoking indicators with DNAmPhenoAge acceleration in a longitudinal aging study in eastern Massachusetts. DNA methylation was measured in whole blood samples from multiple visits for 692 male participants in the Veterans Affairs Normative Aging Study during 1999–2013. Acceleration was defined using residuals from linear regression of the DNAmPhenoAge on the chronological age. Cumulative smoking (pack-years) was significantly associated with DNAmPhenoAge acceleration, whereas self-reported smoking status was not. We observed significant validated associations between smoking-related loci and DNAmPhenoAge acceleration for 52 CpG sites, where 18 were hypomethylated and 34 were hypermethylated, mapped to 16 genes. The AHRR gene had the most loci (N = 8) among the 16 genes. We generated a smoking aging index based on these 52 loci, which showed positive significant associations with DNAmPhenoAge acceleration. These epigenetic biomarkers may help to predict age-related risks driven by smoking. Full article

Background: Associations between prenatal household air pollution (HAP) exposure or cookstove intervention to reduce HAP and cord blood mononuclear cell (CBMC) mitochondrial deoxyribonucleic acid copy number (mtDNAcn), an oxidative stress biomarker, are unknown. Materials and Methods: Pregnant women were recruited and randomized to one of two cookstove interventions, including a clean-burning liquefied petroleum gas (LPG) stove, or control. Prenatal HAP exposure was determined by serial, personal carbon monoxide (CO) measurements. CBMC mtDNAcn was measured by quantitative polymerase chain reaction. Multivariable linear regression determined associations between prenatal CO and cookstove arm on mtDNAcn. Associations between mtDNAcn and birth outcomes and effect modification by infant sex were explored. Results: LPG users had the lowest CO exposures (p = 0.02 by ANOVA). In boys only, average prenatal CO was inversely associated with mtDNAcn (β = -14.84, SE = 6.41, p = 0.03, per 1ppm increase in CO). When examined by study arm, LPG cookstove had the opposite effect in all children (LPG β = 19.34, SE = 9.72, p = 0.049), but especially boys (β = 30.65, SE = 14.46, p = 0.04), as compared to Control. Increased mtDNAcn was associated with improved birth outcomes. Conclusions: Increased prenatal HAP exposure reduces CBMC mtDNAcn, suggesting cumulative prenatal oxidative stress injury. An LPG stove intervention may reverse this effect. Boys appear most susceptible. Full article

Adequate nutrition is important for neurodevelopment. Although nutrients are ingested in combination, the impact of specific nutrients within the context of a nutrient mixture has not been studied with respect to health, such as neurodevelopment. Therefore, we examined the impact of prenatal and childhood nutrient mixtures on neurodevelopmental outcomes. Participants included mother–child pairs in the Programming Research in Obesity, Growth, Environment, and Social Stress (PROGRESS) prospective birth cohort in Mexico City. We assessed prenatal and child micro- and macronutrient profiles among 65 and 329 children, respectively, via food frequency questionnaires. Neurodevelopmental outcomes of 4–6 year-old children were measured using the McCarthy Scales of Children’s Abilities (MSCA). We conducted weighted quantile sum (WQS) regression analyses to calculate indices reflecting “good” and “poor” prenatal and childhood nutrition. After adjusting for maternal education, socioeconomic status, the Home Observation for Measurement of the Environment (HOME) score, and total caloric intake, the good prenatal and childhood nutrition indices predicted more favorable neurodevelopment, while both poor nutrition indices predicted poorer neurodevelopment. These associations were stronger in prenatal than childhood models. Monounsaturated fats predicted various neurodevelopmental abilities relatively strongly in both models. Prenatal and childhood consumption of combinations of beneficial nutrients may contribute to more favorable neurodevelopment. Full article

The U.S. Environmental Protection Agency (EPA) recently issued a notice of violation against Volkswagen (VW) for installing a defective device in certain models of diesel cars to circumvent emission tests for nitrogen oxides (NO_x). We quantified the health and economic impacts of extra NO_x emissions attributable to non-compliant vehicles in the U.S. using the EPA’s Co-Benefits Risk Assessment model. We estimated that the total extra NO_x emitted over one year of operation would result in 5 to 50 premature deaths, 687 to 17,526 work days with restricted activity, and economic costs of $43,479,189 to $423,268,502, based on various assumptions regarding emission scenarios and risks. This study highlights the potential impacts of VW vehicles’ lack of compliance on the health and well-being of the U.S. population. Full article