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The interplay between ECTO and ENDO exposomes on metabolic diseases through lifespan: exposome loop as a new concept
Abstract
The exposome encompasses the total exposure an individual experiences throughout their life, comprising components influenced by the person's genetic, epigenetic and intrinsic and age-related traits (healthy ENDO-exposome), as well as diet, environmental factors and pollutants, habits, and socio-cultural and socio-economic aspects (ECTO-exposome). These elements interact and impact the organism, potentially leading to diseases (unhealthy ENDO-exposome). Metabolic diseases and cancer are a priority for research due to their rising prevalence. Different life stages create windows of susceptibility to external exposures. The ECTO-exposome that leads to metabolic diseases and cancer can occur from pre-birth in utero to postnatal periods, including infancy, childhood, adolescence, and adulthood. Additionally, we propose the concept of the ‘exposome loop’, which is defined as the response of an unhealthy ENDO-exposome to the ECTO-exposome.
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Recent scientific results indicate that diet is the primary source of exposure to endocrine-disrupting chemicals (EDCs) due to their use in food processing, pesticides, fertilizers, and migration from packaging to food, particularly in plastic or canned foods. Although EDCs are not listed on nutrition labels, their migration from packaging to food could inadvertently lead to food contamination, affecting individuals by inhalation, ingestion, and direct contact. The aim of our narrative review is to investigate the role of phthalates and bisphenol A (BPA) in foods, assessing their risks for precocious puberty (PP) and early-onset obesity, which are two clinical entities that are often associated and that share common pathogenetic mechanisms. The diverse outcomes observed across different studies highlight the complexity of phthalates and BPA effects on the human body, both in terms of early puberty, particularly in girls, and obesity with its metabolic disruptions. Moreover, obesity, which is independently linked to early puberty, might confound the relationship between exposure to these EDCs and pubertal timing. Given the potential public health implications, it is crucial to adopt a precautionary approach, minimizing exposure to these EDCs, especially in vulnerable populations such as children.
Regulatory T cells are fundamental for the induction and maintenance of immune homeostasis, with their dysfunction resulting in uncontrolled immune responses and tissue destruction predisposing to autoimmunity, transplant rejection and several inflammatory and metabolic disorders. Recent discoveries have demonstrated that metabolic processes and mitochondrial function are critical for the appropriate functioning of these cells in health, with their metabolic adaptation, influenced by microenvironmental factors, seen in several pathological processes. Upon activation regulatory T cells rearrange their oxidation-reduction (redox) system, which in turn supports their metabolic reprogramming, adding a layer of complexity to our understanding of cellular metabolism. Here we review the literature surrounding redox homeostasis and metabolism of regulatory T cells to highlight new mechanistic insights of these interlinked pathways in immune regulation.
Cumulative xenobiotic exposure has an environmental and human health impact which is currently assessed under the One Health approach. Bisphenol A (BPA) exposure and its potential link with childhood obesity that has parallelly increased during the last decades deserve special attention. It stands during prenatal or early life and could trigger comorbidities and non-communicable diseases along life. Accumulation in the nature of synthetic chemicals supports the “environmental obesogen” hypothesis, such as BPA. This estrogen-mimicking xenobiotic has shown endocrine disruptive and obesogenic effects accompanied by gut microbiota misbalance that is not yet well elucidated. This study aimed to investigate specific microbiota taxa isolated and selected by direct BPA exposure and reveal its role on the overall children microbiota community and dynamics, driving toward specific obesity dysbiosis. A total of 333 BPA-resistant isolated species obtained through culturing after several exposure conditions were evaluated for their role and interplay with the global microbial community. The selected BPA-cultured taxa biomarkers showed a significant impact on alpha diversity. Specifically, Clostridium and Romboutsia were positively associated promoting the richness of microbiota communities, while Intestinibacter, Escherichia-Shigella, Bifidobacterium, and Lactobacillus were negatively associated. Microbial community dynamics and networks analyses showed differences according to the study groups. The normal-weight children group exhibited a more enriched, structured, and connected taxa network compared to overweight and obese groups, which could represent a more resilient community to xenobiotic substances. In this sense, subnetwork analysis generated with the BPA-cultured genera showed a correlation between taxa connectivity and more diverse potential enzymatic BPA degradation capacities.
IMPORTANCE
Our findings indicate how gut microbiota taxa with the capacity to grow in BPA were differentially represented within differential body mass index children study groups and how these taxa affected the overall dynamics toward patterns of diversity generally recognized in dysbiosis. Community network and subnetwork analyses corroborated the better connectedness and stability profiles for normal-weight group compared to the overweight and obese groups.
The escalating prevalence of metabolic and cardiometabolic disorders, often characterized by oxidative stress and chronic inflammation, poses significant health challenges globally. As the traditional therapeutic approaches may sometimes fall short in managing these health conditions, attention is growing toward nutraceuticals worldwide; with compounds being obtained from natural sources with potential therapeutic beneficial effects being shown to potentially support and, in some cases, replace pharmacological treatments, especially for individuals who do not qualify for conventional pharmacological treatments. This review delves into the burgeoning field of nutraceutical-based pharmacological modulation as a promising strategy for attenuating oxidative stress and inflammation in metabolic and cardiometabolic disorders. Drawing from an extensive body of research, the review showcases various nutraceutical agents, such as polyphenols, omega-3 fatty acids, and antioxidants, which exhibit antioxidative and anti-inflammatory properties. All these can be classified as novel nutraceutical-based drugs that are capable of regulating pathways to mitigate oxidative-stress- and inflammation-associated metabolic diseases. By exploring the mechanisms through which nutraceuticals interact with oxidative stress pathways and immune responses, this review highlights their potential to restore redox balance and temper chronic inflammation. Additionally, the challenges and prospects of nutraceutical-based interventions are discussed, encompassing bioavailability enhancement, personalized treatment approaches, and clinical translation. Through a comprehensive analysis of the latest scientific reports, this article underscores the potential of nutraceutical-based pharmacological treatment modulation as a novel avenue to fight oxidative stress and inflammation in the complex landscape of metabolic disorders, particularly accentuating their impact on cardiovascular health.
Endocrine disruptors (EDCs) are chemicals that interfere with the endocrine system. EDC exposure may contribute to the development of obesity, type 2 diabetes, and cardiovascular diseases by impacting the composition of an infant’s gut microbiota during the first 1000 days of life. To explore the relationship between maternal urinary levels of Bisphenol-A and phthalates (UHPLC-MS/MS), and the composition of the infant gut microbiota (16S rDNA) at age 12 months (T3) and, retrospectively, at birth (T0), 1 month (T1), and 6 months (T2), stool samples from 20 infants breastfed at least once a day were analyzed. Metataxonomic bacteria relative abundances were correlated with EDC values. Based on median Bisphenol-A levels, infants were assigned to the over-exposed group (O, n = 8) and the low-exposed group (B, n = 12). The B-group exhibited higher gut colonization of the Ruminococcus torques group genus and the O-group showed higher abundances of Erysipelatoclostridium and Bifidobacterium breve. Additionally, infants were stratified as high-risk (HR, n = 12) or low-risk (LR, n = 8) exposure to phthalates, based on the presence of at least three phthalates with concentrations exceeding the cohort median values; no differences were observed in gut microbiota composition. A retrospective analysis of gut microbiota (T0–T2) revealed a disparity in β-diversity between the O-group and the B-group. Considering T0–T3, the Linear Discriminant Effect Size indicated differences in certain microbes between the O-group vs. the B-group and the HR-group vs. the LR-group. Our findings support the potential role of microbial communities as biomarkers for high EDC exposure levels. Nevertheless, further investigations are required to deeply investigate this issue.
Establishing the infant’s gut microbiota has long-term implications on health and immunity. Breastfeeding is recognized as the best practice of infant nutrition in comparison with formula feeding. We evaluated the effects of the primary feeding practices by analyzing the infant growth and the potential association with gut diseases. A cross-sectional and observational study was designed. This study included 55 mothers with infants, who were divided according to their feeding practices in breastfeeding (BF), formula feeding (FF), and combined breast and formula feeding (CF). Anthropometric measurements of the participants were recorded. Additionally, non-invasive fecal samples from the infants were collected to analyze the microbiota by sequencing, immunoglobulin A (IgA) concentration (ELISA), and volatile organic compounds (gas chromatography with an electronic nose). Results showed that the microbiota diversity in the BF group was the highest compared to the other two groups. The IgA levels in the BF group were twice as high as those in the FF group. Moreover, the child´s growth in the BF group showed the best infant development when the data were compared at birth to the recollection time, as noted by the correlation with a decreased concentration of toxic volatile organic compounds. Interestingly, the CF group showed a significant difference in health status when the data were compared with the FF group. We conclude that early health practices influence children’s growth, which is relevant to further research about how those infants’ health evolved.
Simple Summary
Lung cancer (LC) is considered one of the most common cancers globally. Numerous studies have determined the relations between E-cigarette, or vaping, products (EVPs) and many proven environmental toxicants in LC development. Even though tobacco smoke remains the chief cause of LC, there is increasing concern that EVPs use could also increase LC risk. Consumption of EVPs has been dramatically increasing world-wide, particularly among younger people and non-smokers. This review seeks to consolidate the known environmental toxicants and EVPs contributing to LC to ensure that future research endeavors may identify key focus areas. Thus, EVPs are a highly potential risk factor for LC and an area of significant concern for the future. Since these factors have been linked to the development of LC, more research is needed to determine the mechanisms by which they affect lung pathology. Discovering the pathophysiology of EVPs use and environmental toxicant exposure in LC development can facilitate the adoption of exposure reduction strategies.
Abstract
Lung cancer (LC) is the second-most prevalent tumor worldwide. According to the most recent GLOBOCAN data, over 2.2 million LC cases were reported in 2020, with an estimated new death incident of 1,796,144 lung cancer cases. Genetic, lifestyle, and environmental exposure play an important role as risk factors for LC. E-cigarette, or vaping, products (EVPs) use has been dramatically increasing world-wide. There is growing concern that EVPs consumption may increase the risk of LC because EVPs contain several proven carcinogenic compounds. However, the relationship between EVPs and LC is not well established. E-cigarette contains nicotine derivatives (e.g., nitrosnornicotine, nitrosamine ketone), heavy metals (including organometal compounds), polycyclic aromatic hydrocarbons, and flavorings (aldehydes and complex organics). Several environmental toxicants have been proven to contribute to LC. Proven and plausible environmental carcinogens could be physical (ionizing and non-ionizing radiation), chemicals (such as asbestos, formaldehyde, and dioxins), and heavy metals (such as cobalt, arsenic, cadmium, chromium, and nickel). Air pollution, especially particulate matter (PM) emitted from vehicles and industrial exhausts, is linked with LC. Although extensive environmental exposure prevention policies and smoking reduction strategies have been adopted globally, the dangers remain. Combined, both EVPs and toxic environmental exposures may demonstrate significant synergistic oncogenicity. This review aims to analyze the current publications on the importance of the relationship between EVPs consumption and environmental toxicants in the pathogenesis of LC.
Studies have implicated arsenic exposure in various pathological conditions, including metabolic disorders, which have become a global phenomenon, affecting developed, developing, and under-developed nations. Despite the huge risks associated with arsenic exposure, humans remain constantly exposed to it, especially through the consumption of contaminated water and food. This present study provides an in-depth insight into the mechanistic pathways involved in the metabolic derangement by arsenic. Compelling pieces of evidence demonstrate that arsenic induces metabolic disorders via multiple pathways. Apart from the initiation of oxidative stress and inflammation, arsenic prevents the phosphorylation of Akt at Ser473 and Thr308, leading to the inhibition of PDK-1/Akt insulin signaling, thereby reducing GLUT4 translocation through the activation of Nrf2. Also, arsenic downregulates mitochondrial deacetylase Sirt3, decreasing the ability of its associated transcription factor, FOXO3a, to bind to the agents that support the genes for manganese superoxide dismutase and PPARg co-activator (PGC)-1a. In addition, arsenic activates MAPKs, modulates p53/ Bcl-2 signaling, suppresses Mdm-2 and PARP, activates NLRP3 inflammasome and caspase-mediated apoptosis, and induces ER stress, and ox-mtDNA-dependent mitophagy and autophagy. More so, arsenic alters lipid metabolism by decreasing the presence of 3-hydroxy-e-methylglutaryl-CoA synthase 1 and carnitine O-octanoyl transferase (Crot) and increasing the presence of fatty acid-binding protein-3 mRNA. Furthermore, arsenic promotes atherosclerosis by inducing endothelial damage. This cascade of pathophysiological events promotes metabolic derangement. Although the pieces of evidence provided by this study are convincing, future studies evaluating the involvement of other likely mechanisms are important. Also, epidemiological studies might be necessary for the translation of most of the findings in animal models to humans.
Background
A relationship between smoking and interpersonal influences has been well established within the literature. There have been cultural shifts in denormalisation and a reduction in tobacco smoking in many countries. Hence there is a need to understand social influences on adolescents’ smoking across smoking normalisation contexts.
Methods
The search was conducted in July 2019 and updated in March 2022 within 11 databases and secondary sources. Search terms included schools, adolescents, smoking, peers, social norms and qualitative research. Screening was conducted by two researchers independently and in duplicate. Study quality was assessed using the eight-item Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-centre) tool for the appraisal of qualitative studies. Results were synthesised using a meta-narrative lens for meta-ethnography and compared across smoking normalisation contexts.
Results
Forty one studies were included and five themes were developed, mapping onto the socio ecological model. The social processes by which adolescents take up smoking differed according to a mixture of school type, peer group structure and the smoking culture within the school, as well as the wider cultural context. Data available from smoking denormalised contexts, described changes in social interactions around smoking to cope with its stigmatisation. This was manifested through i) direct peer influence, whereby subtle techniques were employed, ii) group belonging whereby smoking was less likely to be seen as a key determinant of group membership and smoking was less commonly reported to be used as a social tool, and iii) popularity and identity construction, whereby smoking was perceived more negatively in a denormalised context, compared with a normalised context.
Conclusions
This meta-ethnography is the first study to demonstrate, drawing on international data, that peer processes in adolescent smoking may undergo changes as smoking norms within society change. Future research should focus on understanding differences across socioeconomic contexts, to inform the adaptation of interventions.
The NHGRI-EBI GWAS Catalog (www.ebi.ac.uk/gwas) is a FAIR knowledgebase providing detailed, structured, standardised and interoperable genome-wide association study (GWAS) data to >200 000 users per year from academic research, healthcare and industry. The Catalog contains variant-trait associations and supporting metadata for >45 000 published GWAS across >5000 human traits, and >40 000 full P-value summary statistics datasets. Content is curated from publications or acquired via author submission of prepublication summary statistics through a new submission portal and validation tool. GWAS data volume has vastly increased in recent years. We have updated our software to meet this scaling challenge and to enable rapid release of submitted summary statistics. The scope of the repository has expanded to include additional data types of high interest to the community, including sequencing-based GWAS, gene-based analyses and copy number variation analyses. Community outreach has increased the number of shared datasets from under-represented traits, e.g. cancer, and we continue to contribute to awareness of the lack of population diversity in GWAS. Interoperability of the Catalog has been enhanced through links to other resources including the Polygenic Score Catalog and the International Mouse Phenotyping Consortium, refinements to GWAS trait annotation, and the development of a standard format for GWAS data.
Background
Mixture risk assessments require reference doses for common health endpoints of all the chemicals to be considered together. In support of a mixture risk assessment for male reproductive health, we conducted a systematic review of the literature on associations between exposures to Polychlorinated Biphenyls (PCBs) and declines in semen quality. PCBs can act as Aryl-hydrocarbon Receptor (AhR)-agonists and Androgen Receptor (AR)-antagonists, both mechanisms which can affect sperm parameters. PCBs and other AR-antagonists can produce additive combination effects. Based on these observations our objective was to systematically gather data from animal and human studies to derive a reference dose for declines in semen quality for individual PCB.
Methods
We systematically reviewed and evaluated the evidence in human epidemiological and experimental animal studies on associations between PCBs and deteriorations in semen quality. Human data and findings from animal studies with PCB mixtures were considered as supporting evidence. Information for individual congeners from animal studies was required for inclusion in mixture risk assessment. Using a robust confidence rating approach, we identified suitable studies to derive reference doses for individual PCB congeners.
Results
Evaluation of human epidemiological studies revealed several reports of adverse effects on sperm parameters linked to PCB exposures, although some studies reported improved semen quality. Our review of experimental animal studies found that treatments with PCBs affected semen quality, in most cases adversely. We found robust evidence that PCB-118 and -169 were linked to declines in semen quality. Evidence for adverse effects of PCB-126, -132, -149, and -153 was moderate, whereas for PCB-77 it was slight and for PCB-180 indeterminate. Using widely accepted risk assessment procedures, we estimated reference dose values of 0.0029 µg/kg/day for PCB-118 and 0.00533 µg/kg/day for PCB-169. In addition, we derived values for PCB-126: 0.000073 µg/kg/day, PCB-132: 0.0228 µg/kg/day, PCB-149: 0.656 µg/kg/day, and PCB-153: 0.0058 µg/kg/day.
Conclusions
We found robust evidence for links between PCB exposure and deteriorations in semen quality, and derived reference doses for a set of congeners. We intend to use these values in combination with congener-specific exposure data in a mixture risk assessment for declines in semen quality, involving several other antiandrogenic chemicals.
BPA is one of the most common endocrine disruptors that is widely being manufactured daily nationwide. Although scientific evidence supports claims of negative effects of BPA on humans, there is also evidence suggesting that a low level of BPA is safe. However, numerous in vivo trials contraindicate with this claim and there is a high possibility of BPA exposure could lead to obesity. It has been speculated that this does not stop with the exposed subjects only, but may also cause transgenerational effects. Direct disruption of endocrine regulation, neuroimmune and signaling pathways, as well as gut microbiata, has been identified to be interrupted by BPA exposure, leading to overweight or obesity. In these instances, cardiovascular complications are one of the primary notable clinical signs. In regard to this claim, this review paper discusses the role of BPA on obesity in the perspective of endocrine disruptions and possible cardiovascular complications that may arise due to BPA. Thus, the aim of this review is to outline the changes in gut microbiota and neuroimmune or signaling mechanisms involved in obesity in relation to BPA. To identify potentially relevant articles, a depth search was done on the databases Nature, PubMed, Wiley Online Library, and Medline & Ovid from the past 5 years. According to Boolean operator guideline, selected keywords such as (1) BPA OR environmental chemical AND fat OR LDL OR obese AND transgenerational effects or phenocopy (2) Endocrine disruptors OR chemical AND lipodystrophy AND phenocopy (3) Lipid profile OR weight changes AND cardiovascular effect (4) BPA AND neuroimmune OR gene signaling, were used as search terms. Upon screening, 11 articles were finalized to be further reviewed and data extraction tables containing information on (1) the type of animal model (2) duration and dosage of BPA exposure (3) changes in the lipid profile or weight (4) genes, signaling mechanism, or any neuroimmune signal involved, and (5) transgenerational effects were created. In toto, the study indicates there are high chances of BPA exposure affecting lipid profile and gene associated with lipolysis, leading to obesity. Therefore, this scoping review recapitulates the possible effects of BPA that may lead to obesity with the evidence of current in vivo trials. The biomarkers, safety concerns, recommended dosage, and the impact of COVID-19 on BPA are also briefly described.
Increasing prevalence of metabolic syndrome (MetS) is causing a significant health burden among the European population. Current knowledge supports the notion that endocrine-disrupting chemicals (EDCs) interfere with human metabolism and hormonal balance, contributing to the conventionally recognized lifestyle-related MetS risk factors. This review aims to identify epidemiological studies focusing on the association between MetS or its individual components (e.g., obesity, insulin resistance, diabetes, dyslipidemia and hypertension) and eight HBM4EU priority substances (bisphenol A (BPA), per- and polyfluoroalkyl substances (PFASs), phthalates, polycyclic aromatic hydrocarbons (PAHs), pesticides and heavy metals (cadmium, arsenic and mercury)). Thus far, human biomonitoring (HBM) studies have presented evidence supporting the role of EDC exposures on the development of individual MetS components. The strength of the association varies between the components and EDCs. Current evidence on metabolic disturbances and EDCs is still limited and heterogeneous, and mainly represent studies from North America and Asia, highlighting the need for well-conducted and harmonized HBM programmes among the European population. Rigorous and ongoing HBM in combination with health monitoring can help to identify the most concerning EDC exposures, to guide future risk assessment and policy actions.
Resumen
El desarrollo de la medicina del sueño ha experimentado notables avances por contribuciones provenientes tanto de las ciencias básicas como de los estudios clínicos, destacando una relación positiva entre la preservación de un sueño normal y un amplio espectro de beneficios en diferentes indicadores de salud individual y de la población.
Un adecuado conocimiento de los postulados y mecanismos fisiológicos del sueño actualmente más aceptados a escala molecular, celular y sistémica, permiten desarrollar conceptos objetivos que otorgan mayor solidez a la evaluación del sueño. La etapificación del sueño, su arquitectura, variables de continuidad del mismo, asícomo el índice de microdespertares, entre otros, tienen una aplicación clínica directa: se pueden describir y utilizar rangos normales de parámetros polisomnográficos con sus características a lo largo de la edad, y variantes cronotípicas individuales. De este modo, se espera seguir avanzando tanto en el temprano y correcto diagnóstico como en una mejor toma de decisiones médicas.
Muy probablemente, debido a la función integradora del sueño, es que este juega un rol tan crucial en la salud, avalado por un cuerpo de evidencia que muestra un importante impacto beneficioso de un sueño sano en la calidad de vida, morbilidad y la prevención primaria de enfermedades muy variadas.
Infant ' s feeding patterns are important for development and growth; therefore babies are very sensitive to toxic elements, mainly through their food, so in the present study, the concentrations and daily intake of some Toxic Elements (TEs); Lead (Pb), Arsenic (As), Cadmium (Cd), Mercury (Hg) and Aluminum (Al) were measured in different and random 60 dried infant foods {30 infant formula (0-6 months) and 30 milk-cereal based infant formula (6 months)} which obtained from various supermarkets and pharmacies. The analysis was done using Inductive Coupled Plasma-Mass Spectrometer (ICP-MS). It could be determined the lead, arsenic, cadmium, mercury and aluminum by mean values of 0.424±0.006, 0.205±0.003, 0.014±0.0001, 0.298±0.007 and 0.464±0.029 mg/kg in the examined infant milk formula samples and a ranged minimum to maximum concentrations of 0.114-0.177, 0.155-0.293, 0.014-0.015, 0.282-0.310 and 0.287-0.437mg/kg, respectively in the examined milk-cereal based infant formula. Present study indicates that, the greater level of contamination of examined infant formula samples with toxic elements (lead and mercury) surpasses the maximum limit and Provisional Tolerable Daily Intake (PTDI) of these elements. Mercury is over PTDI (0.0005 mg/kg bwt/day) in all milk-cereal based infant formula samples, also arsenic in all examined samples of this type of formula was exceed the maximum limit (0.05 mg/kg) of Indian standard. This investigation shows such types of infant formula need more amendment to set limit of more toxic metals for this sensitive group of population.
Background
Microglial activation-mediated neuroinflammation plays an important role in the progression of neurodegenerative diseases. Inflammatory activation of microglial cells is often accompanied by a metabolic switch from oxidative phosphorylation to aerobic glycolysis. However, the roles and molecular mechanisms of glycolysis in microglial activation and neuroinflammation are not yet fully understood.
Methods
The anti-inflammatory effects and its underlying mechanisms of glycolytic inhibition in vitro were examined in lipopolysaccharide (LPS) activated BV-2 microglial cells or primary microglial cells by enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot, immunoprecipitation, flow cytometry, and nuclear factor kappa B (NF-κB) luciferase reporter assays. The anti-inflammatory and neuroprotective effects of glycolytic inhibitor, 2-deoxoy- d -glucose (2-DG) in vivo were measured in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-or LPS-induced Parkinson’s disease (PD) models by immunofluorescence staining, behavior tests, and Western blot analysis.
Results
We found that LPS rapidly increased glycolysis in microglial cells, and glycolysis inhibitors (2-DG and 3-bromopyruvic acid (3-BPA)), siRNA glucose transporter type 1 (Glut-1), and siRNA hexokinase (HK) 2 abolished LPS-induced microglial cell activation. Mechanistic studies demonstrated that glycolysis inhibitors significantly inhibited LPS-induced phosphorylation of mechanistic target of rapamycin (mTOR), an inhibitor of nuclear factor-kappa B kinase subunit beta (IKKβ), and NF-kappa-B inhibitor alpha (IκB-α), degradation of IκBα, nuclear translocation of p65 subunit of NF-κB, and NF-κB transcriptional activity. In addition, 2-DG significantly inhibited LPS-induced acetylation of p65/RelA on lysine 310, which is mediated by NAD-dependent protein deacetylase sirtuin-1 (SIRT1) and is critical for NF-κB activation. A coculture study revealed that 2-DG reduced the cytotoxicity of activated microglia toward MES23.5 dopaminergic neuron cells with no direct protective effect. In an LPS-induced PD model, 2-DG significantly ameliorated neuroinflammation and subsequent tyrosine hydroxylase (TH)-positive cell loss. Furthermore, 2-DG also reduced dopaminergic cell death and microglial activation in the MPTP-induced PD model.
Conclusions
Collectively, our results suggest that glycolysis is actively involved in microglial activation. Inhibition of glycolysis can ameliorate microglial activation-related neuroinflammatory diseases.
Gestational diabetes mellitus (GDM) shows a deficiency in the metabolism of D‐glucose and other nutrients, thereby negatively affecting the fetoplacental vascular endothelium. Maternal hyperglycaemia and hyperinsulinemia play an important role in the aetiology of GDM. A combination of these and other factors predisposes women to developing GDM with pre‐pregnancy normal weight, viz. classic GDM. However, women with GDM and pre‐pregnancy obesity (gestational diabesity, GDty) or overweight (GDMow) show a different metabolic status than women with classic GDM. GDty and GDMow are associated with altered L‐arginine/nitric oxide and insulin/adenosine axis signalling in the human fetoplacental microvascular and macrovascular endothelium. These alterations differ from those observed in classic GDM. Here, we have reviewed the consequences of GDty and GDMow in the modulation of fetoplacental endothelial cell function, highlighting studies describing the modulation of intracellular pH homeostasis and the potential implications of NO generation and adenosine signalling in GDty‐associated fetal vascular insulin resistance. Moreover, with an increase in the rate of obesity in women of childbearing age worldwide, the prevalence of GDty is expected to increase in the next decades. Therefore, we emphasise that women with GDty and GDMow should be characterized with a different metabolic state from that of women with classic GDM to develop a more specific therapeutic approach for protecting the mother and fetus.
Background
As sleep-related difficulties are a growing public health concern, it is important to gain an overview of the specific difficulty areas of the most vulnerable individuals: children. The current descriptive study presents the prevalence of sleep-related difficulties in two large samples of healthy children and adolescents and outlines the effects of age, gender, and socioeconomic status (SES) on various sleep-related difficulties.
Methods
Participants were 855 4–9 year-old children (child sample) and 1,047 10–17 year-old adolescents (adolescent sample) participating 2011–2015 in the LIFE Child study, a population-based cohort study in Germany. Parents of the child participants completed the Children’s Sleep Habits Questionnaire (CSHQ), whereas adolescents self-administered the Sleep Self Report (SSR). Familial SES was determined by a composite score considering parental education, occupational status, and income. Multiple regression analyses were carried out to address the research question.
Results
Among 4−9 year-old children, the mean bedtime was reported to be 8 p.m., the mean wake-up time 7 a.m., and sleep duration decreased by 14 min/year of age. 22.6 % of the children and 20.0 % of the adolescents showed problematic amounts of sleep-related difficulties. In the child sample, bedtime resistance, sleep onset delay, sleep-related anxiety, night waking, and parasomnia were more frequent in younger than older children. In the adolescent sample, difficulties at bedtime were more frequent among the younger adolescents, whereas daytime sleepiness was more prominent in the older than the younger adolescents. Considering gender differences, sleep-related difficulties were more frequent among boys in the child sample and among girls in the adolescent sample. Lower SES was associated with increased sleep-related difficulties in the adolescent, but not the child sample.
Conclusions
The present results report sleep-related difficulties throughout both childhood and adolescence. Gender differences can already be observed in early childhood, while effects of SES emerge only later in adolescence. The awareness for this circumstance is of great importance for pediatric clinicians who ought to early identify sleep-related difficulties in particularly vulnerable individuals.
Pregnancy represents a time of dramatic physiological adaptation by the mother in which dramatic changes in maternal cardiovascular, metabolic and immune systems occur. These adaptations, initiated from the earliest stages of gestation, are crucial for the implantation and continued development of the embryo, the establishment of the placenta and the growth of the fetus. Impairments in the normal adaptation of the maternal cardiovascular, metabolic and immune systems underlie the aetiology of gestational disorders such as preeclampsia and gestational diabetes. Studies have shown that the development of such gestational complications not only affects the well-being of the mother but also the short- and long-term health of her offspring. While the connection between maternal lifestyle factors and the development of gestational disorders such as preeclampsia and gestational diabetes has been studied in detail, the link between a father’s lifestyle and the well-being of the mother during pregnancy has received less attention. In this review we will explore the evidence that a range of paternal factors, such as age and diet, at the time of conception can not only affect the development of his offspring, but also the well-being of the mother during pregnancy. In addition, we will examine the sperm- and seminal plasma-specific mechanisms that connect the health of the father with that of the mother and his offspring.
Background:
In children and adolescents, chronic low-grade inflammation has been implicated in the pathogenesis of co- and multi-morbid conditions to mental health disorders. Diet quality is a potential mechanism of action that can exacerbate or ameliorate low-grade inflammation; however, the exact way dietary intake can regulate the immune response in children and adolescents is still to be fully understood.
Methods:
Studies that measured dietary intake (patterns of diet, indices, food groups, nutrients) and any inflammatory biomarkers in children and adolescents aged 2 to19 years and published until November 2020 were included in this systematic review, and were selected in line with PRISMA guidelines through the following databases: Academic Search Complete, CINAHL, Global Health, Medline COMPLETE and Web of Science-Core Collection. A total of 53 articles were identified.
Results:
Results show that adequate adherence to healthful dietary patterns such as the Mediterranean diet, or food groups such as vegetables and fruit, or macro/micro nutrients such as fibre or vitamin C and E, are associated with decreased levels of pro-inflammatory biomarkers, mainly c-reactive protein (CRP), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α), whereas adherence to a Western dietary pattern, as well as intake of food groups such as added sugars, macro-nutrients such as saturated fatty acids or ultra-processed foods, is associated with higher levels of the same pro-inflammatory biomarkers.
Conclusions:
This is the first systematic review examining dietary intake and biological markers of inflammation in both children and adolescents. A good quality diet, high in vegetable and fruit intake, wholegrains, fibre and healthy fats ameliorates low-grade inflammation, and therefore represents a promising therapeutic approach, as well as an important element for disease prevention in both children and adolescents.
Purpose: To examine the prospective relevance of dietary sugar intake (based on dietary data as well as urinary excretion data) in adolescent years for insulin sensitivity and biomarkers of inflammation in young adulthood.
Methods: Overall 254 participants of the DONALD study who had at least two 3-day weighed dietary records for calculating intakes of fructose, glucose, sucrose, total, free, added sugars, total sugars from sugar-sweetened beverages (SSB), juice, and sweets/sugar or at least two complete 24 h urine samples (n = 221) for calculating sugar excretion (urinary fructose and urinary fructose + sucrose) in adolescence (females: 9–15 years, males: 10–16 years) and a fasting blood sample in adulthood (18–36 years), were included in multivariable linear regression analyses assessing their prospective associations with adult homeostasis model assessment insulin sensitivity (HOMA2-%S) and a pro-inflammatory score (based on CRP, IL-6, IL-18, leptin, chemerin, adiponectin).
Results: On the dietary intake level, no prospective associations were observed between adolescent fructose, sucrose, glucose, added, free, total sugar, or total sugar from SSB, juice or sweets/sugar intake and adult HOMA2-%S (p > 0.01). On the urinary level, however, higher excreted fructose levels were associated with improved adult HOMA2-%S (p = 0.008) among females only. No associations were observed between dietary or urinary sugars and the adult pro-inflammatory score (p > 0.01).
Conclusion: The present study did not provide support that dietary sugar consumed in adolescence is associated with adult insulin sensitivity. The one potential exception was the moderate dietary consumption of fructose, which showed a beneficial association with adult fasting insulin and insulin sensitivity.
Arsenic is a toxic heavy metal vastly dispersed all over the earth crust. It manifests several major adverse health issues to millions of arsenic exposed populations. Arsenic is associated with different types of cancer, cardiovascular disorders, diabetes, hypertension and many other diseases. On the contrary, arsenic (arsenic trioxide, As2O3) is used as a chemotherapeutic agent in the treatment of acute promyelocytic leukemia. Balance between arsenic induced cellular proliferations and apoptosis finally decide the outcome of its transformation rate. Arsenic propagates signals via cellular and nuclear pathways depending upon the chemical nature, and metabolic-fates of the arsenical compounds. Arsenic toxicity is propagated via ROS induced stress to DNA-repair mechanism and mitochondrial stability in the cell. ROS induced alteration in p53 regulation and some mitogen/ oncogenic functions determine the transformation outcome influencing cyclin-cdk complexes. Growth factor regulator proteins such as c-Jun, c-fos and c-myc are influenced by chronic arsenic exposure. In this review we have delineated arsenic induced ROS regulations of epidermal growth factor receptor (EGFR), NF-ĸβ, MAP kinase, matrix-metalloproteinases (MMPs). The role of these signaling molecules has been discussed in relation to cellular apoptosis, cellular proliferation and neoplastic transformation. The arsenic stimulated pathways which help in proliferation and neoplastic transformation ultimately resulted in cancer manifestation whereas apoptotic pathways inhibited carcinogenesis. Therapeutic strategies against arsenic should be designed taking into account all these factors.
Many additives, some of which have no nutritional value, can be legally used in processed foods. They intensify colour, thicken, increase shelf life and enhance flavour. Regulatory authorities issue approvals as safe within acceptable quantitative limits. Ultra-processed foods (UPFs) contain combinations of all these additives and are particularly attractive to children.
Many publications suggest that artificial colourants, benzoate preservatives, non-caloric sweeteners, emulsifiers and their degradation derivatives have adverse effects by increasing risks of mental health disorders, attention deficit hyperactivity disorder, cardiovascular disease, metabolic syndrome and potential carcinogenic effects.
A systematic review has established that artificial azo dye food colourants (AFCs) and sodium benzoate preservative cause disturbed behaviour in children. AFCs and benzoates in animal models have neurotoxic properties through gut microbial generation of toxic metabolites. Observational studies show associations between high emulsifier intake and cardiovascular disease. Animal models and in vitro studies have highlighted neurotoxic, cytotoxic, genotoxic and carcinogenic effects. High intake of non-caloric sweeteners has been linked to cardiovascular disease and depression in adults and is linked to childhood obesity.
Little research has focused on children who are the largest consumers of UPFs. Potentially, they are a ticking time bomb for adult obesity, metabolic syndrome, cardiovascular diseases, mental health disorders and cancers. Based on risk/benefit analysis, azo dye AFCs should be banned. Benzoates, emulsifiers and sweeteners require assessment of quantitative limits and cumulative effects of combinations. Consumers purchasing UPFs require information through ingredient health warnings and recommendations to use natural unprocessed foods which have well-described health-promoting properties.
Environmental toxicants are chemical substances capable to impair environmental quality and exert adverse effects on humans and other animals. The main routes of exposure to these pollutants are through the respiratory tract, skin, and oral ingestion. When ingested orally, they will encounter trillions of microorganisms that live in a community - the gut microbiota (GM). While pollutants can disrupt the GM balance, GM plays an essential role in the metabolism and bioavailability of these chemical compounds. Under physiological conditions, strategies used by the GM for metabolism and/or excretion of xenobiotics include reductive and hydrolytic transformations, lyase and functional group transfer reactions, and enzyme-mediated functional transformations. Simultaneously, the host performs metabolic processes based mainly on conjugation, oxidation, and hydrolysis reactions. Thus, due to the broad variety of bacterial enzymes present in GM, the repertoire of microbial transformations of chemicals is considered a key component of the machinery involved in the metabolism of pollutants in humans and other mammals. Among pollutants, metals deserve special attention once contamination by metals is a worldwide problem, and their adverse effects can be observed even at very low concentrations due to their toxic properties. In this review, bidirectional interaction between lead, arsenic, cadmium, and mercury and the host organism and its GM will be discussed given the most recent literature, presenting an analysis of the ability of GM to alter the host organism's susceptibility to the toxic effects of heavy metals, as well as evaluating the extent to which interventions targeting the microbiota could be potential initiatives to mitigate the adverse effects resulting from poisoning by heavy metals. This study is the first to highlight the overlap between some of the bacteria found to be altered by metal exposure and the bacteria that also aid the host organism in the metabolism of these metals. This could be a key factor to determine the beneficial species able to minimize the toxicity of metals in future therapeutic approaches.
Bisphenol A (BPA) is an endocrine-disrupting chemical substance responsible for the composition of polycarbonate plastics and epoxy resins. Early life and pregnancy are important windows of susceptibility. This review aimed to conduct a systematic assessment of human studies to comprehensively describe the association between prenatal BPA exposure and neonatal health outcomes. Literature was searched in Cochrane Library, Embase, PubMed, Scopus, and Web of Science published before November 2022, and were selected according to clear inclusion and exclusion criteria. The Newcastle-Ottawa scale (NOS) and Grades of Recommendation, Assessment, Development, and Evaluation guidelines (GRADE) were followed to grade the methodological quality of studies and the certainty of the evidence respectively. As a result, a total of 22259 participants from 45 trials were included. And the potential associations of prenatal exposure to BPA and neonatal health outcomes were mainly shown in four aspects: gestational age/preterm birth, physical health at birth, the incidence of systemic abnormalities or diseases, and other health outcomes. Although the certainty of the evidence was low to very low, the methodological quality of the included studies was high. Prenatal BPA exposure tended to have negative effects on most of the health outcomes in neonates but showed inconsistent results on physical health at birth. This systematic review is the first to comprehensively synthesize the existing evidence on the association between prenatal BPA exposure and neonatal health outcomes. In the future, further studies are still needed to verify these effects and elucidate the underlying mechanisms.
Microbially mediated inorganic-methylated arsenic (As) transformation in paddy soil is crucial to rice safety; however, the linkages between the microbial As methylation process and methylated As species remain elusive. Here, 62 paddy soils were collected from the Mekong River delta of Cambodia to profile As-related functional gene composition involved in the As cycle. The soil As concentration ranged from <1 to 16.6 mg kg-1, with average As contents of approximately 81% as methylated As and 54% as monomethylarsenate (MMAs(V)) in the phosphate- and oxalate-extractable fractions based on As sequential extraction analysis. Quantitative PCR revealed high arsenite-methylating gene (arsM) copy numbers, and metagenomics identified consistently high arsM gene abundance. The abundance of As-related genes was the highest in bacteria, followed by archaea and fungi. Pseudomonas, Bradyrhizobium, Burkholderia, and Anaeromyxobacter were identified as bacteria harboring the most genes related to As biotransformation. Moreover, arsM and arsI (As demethylation) gene-containing operons were identified in the metagenome-assembled genomes (MAGs), implying that arsM and arsI could be transcribed together. The prevalence of methylated As and arsM genes may have been overlooked in tropical paddy fields. The As methylation-demethylation cycle should be considered when manipulating the methylated As pool in paddy fields for rice safety.
The study of the interplay between social factors, environmental hazards and health has garnered much attention in recent years. The term "exposome" was coined to describe the total impact of environmental exposures on an individual's health and wellbeing, serving as a complementary concept to the genome. Studies have shown a strong correlation between the exposome and cardiovascular health, with various components of the exposome having been implicated in the development and progression of cardiovascular disease (CVD). These components include the natural and built environment, air pollution, diet, physical activity, and psychosocial stress, among others. This review provides an overview of the relationship between the exposome and cardiovascular health, highlighting the epidemiological and mechanistic evidence of environmental exposures on CVD. The interplay between various environmental components is discussed, and potential avenues for mitigation are identified.
The environmental toxicity of bisphenol A (BPA) and its analog like bisphenol S (BPS) have drawn wide attention, but their roles in cancer progression remain controversial. Here, we investigated the effect of BPA/BPS on the development of ovarian cancer. Human internal BPA/BPS exposure levels were analyzed from NHANES 2013-2016 data. We treated human ovarian cancer cells with 0-1000 nM BPA/BPS and found that 100 nM BPA/BPS treatment significantly increased Cancer Stem Cell (CSC) markers expression including OCT4, NANOG and SOX2. Cancer cell stemness evaluation induced by BPA/BPS was notably attenuated by the knockdown of PINK1 or Mdivi-1 treatment. The activation of PINK1 initiated mitophagy by inhibiting p-p53 nuclear translocation in a non-canonical manner. In vivo studies validated that BPA/BPS-exposed mice have higher tumor metastasis incidence compared with the control group, while mitophagy inhibition blocked such a promotion effect. In addition, CSC markers such as SOX2 had been found to be overexpressed in the tumor tissues of BPA/BPS exposure group. Taken together, the findings herein first provide the evidence that environmentally relevant BPA/BPS exposure could enhance ovarian cancer cell stemness through a non-canonical PINK1/p53 mitophagic pathway, raising concerns about the potential population hazards of BPA and other bisphenol analogs.
Since ancient times, breastfeeding has been the fundamental way of nurturing the newborn. The benefits of breast milk are widely known, as it is a source of essential nutrients and provides immunological protection, as well as developmental benefits, among others. However, when breastfeeding is not possible, infant formula is the most appropriate alternative. Its composition meets the nutritional requirements of the infant, and its quality is subject to strict control by the authorities. Nonetheless, the presence of different pollutants has been detected in both matrices. Thus, the aim of the present review is to make a comparison between the findings in both breast milk and infant formula in terms of contaminants in the last decade, in order to choose the most convenient option depending on the environmental conditions. For that, the emerging pollutants including metals, chemical compounds derived from heat treatment, pharmaceutical drugs, mycotoxins, pesticides, packaging materials, and other contaminants were described. While in breast milk the most concerning contaminants found were metals and pesticides, in infant formula pollutants such as metals, mycotoxins, and packaging materials were the most outstanding. In conclusion, the convenience of using a feeding diet based on breast milk or either infant formula depends on the maternal environmental circumstances. However, it is important to take into account the immunological benefits of the breast milk compared to the infant formula, and the possibility of using breast milk in combination with infant formula when the nutritional requirements are not fulfilled only with the intake of breast milk. Therefore, more attention should be paid in terms of analyzing these conditions in each case to be able to make a proper decision, as it will vary depending on the maternal and newborn environment.
Fatty acid (FA) metabolism dysfunction of white adipose tissue (WAT) underlies obesity and insulin resistance in response to high calorie intake and/or endocrine-disrupting chemicals (EDCs), among other factors. Arsenic is an EDC that has been associated with metabolic syndrome and diabetes. However, the combined effect of a high-fat diet (HFD) and arsenic exposure on WAT FA metabolism has been little studied. FA metabolism was evaluated in visceral (epididymal and retroperitoneal) and subcutaneous WAT of C57BL/6 male mice fed control or HFD (12 and 40% kcal fat, respectively) for 16 weeks together with an environmentally relevant chronic arsenic exposure through drinking water (100 μg/l) during the second half of the study. In mice fed HFD, arsenic potentiated the increase of serum markers of selective insulin resistance in WAT and fatty acid re-esterification and the decrease in the lipolysis index. Retroperitoneal was the WAT most affected, where the combination of arsenic and HFD in contrast to HFD, generated higher weight, larger adipocytes, increased triglyceride content, and decreased fasting stimulated lipolysis evidenced by lower phosphorylation of HSL and perilipin. At the transcriptional level, arsenic in mice fed either diet downregulated genes involved in fatty acid uptake (LPL, CD36), oxidation (PPARα, CPT1), lipolysis (ADRß3) and glycerol transport (AQP7 and AQP9). Additionally, arsenic potentiated hyperinsulinemia induced by HFD, despite a slight increase in weight gain and food efficiency. Thus, the second hit of arsenic in sensitized mice by HFD worsens fatty acid metabolism impairment in WAT, mainly retroperitoneal, along with an exacerbated insulin resistance phenotype.
Background:
A significant proportion of premature deaths globally are related to metabolic diseases in young adults. We examined the global trends and mortality of metabolic diseases in individuals aged below 40 years using data from the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019.
Methods:
From 2000 to 2019, global estimates of deaths and disability-adjusted life years (DALYs) were described for metabolic diseases (type 2 diabetes mellitus [T2DM], hyperlipidemia, hypertension, obesity, non-alcoholic fatty liver disease [NAFLD]). Subgroup analyses were performed based on sex, geographical regions and Socio-Demographic Index (SDI). Age-standardised death and DALYs were presented per 100,000 population with 95 % uncertainty intervals (UI). Projections of mortality and DALYs were estimated using regression models based on the GBD 2019 data and combining them with Institute for Health Metrics and Evaluation projection counts for years up to 2050.
Results:
In 2019, the highest age-standardised death rates were observed in hypertension (133·88 [121·25-155·73]), followed by obesity (62·59 [39·92-89·13]), hyperlipidemia (56·51 [41·83-73·62]), T2DM (18·49 [17·18-19·66]) and NAFLD (2·09 [1·61-2·60]). Similarly, obesity (1932·54 [1276·61-2639·74]) had the highest age-standardised DALYs, followed by hypertension (2885·57 [2580·75-3201·05]), hyperlipidemia (1207·15 [975·07-1461·11]), T2DM (801·55 [670·58-954·43]) and NAFLD (53·33 [40·73-68·29]). Mortality rates decreased over time in hyperlipidemia (-0·6 %), hypertension (-0·47 %), NAFLD (-0·31 %) and T2DM (-0·20 %), but not in obesity (1·07 % increase). The highest metabolic-related mortality was observed in Eastern Mediterranean and low SDI countries. By 2050, obesity is projected to contribute to the largest number of deaths (102·8 % increase from 2019), followed by hypertension (61·4 % increase), hyperlipidemia (60·8 % increase), T2DM (158·6 % increase) and NAFLD (158·4 % increase), with males continuing to bear the greatest burden across all metabolic diseases.
Conclusion:
The growing burden of metabolic diseases, increasing obesity-related mortality trends, and the sex-regional-socioeconomic disparities evident in young adulthood, underlie the concerning growing global burden of metabolic diseases now and in future.
Funding Acknowledgements
Type of funding sources: None.
Background
A large proportion of premature deaths are related to metabolic diseases in the young adult population. We examined the global trends and mortality of metabolic diseases using estimates from the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019 in individuals aged below 40 years.
Methods
From 2000-2019, global estimates of prevalence, deaths, and disability-adjusted life years (DALYs) were described for metabolic diseases (type 2 diabetes mellitus [T2DM], hypertension, non-alcoholic fatty liver disease [NAFLD]). Global estimates were limited to mortality and DALYs for risk factors (hyperlipidemia and obesity). Subgroup analyses were performed based on sex, geographical regions and Socio-Demographic Index (SDI). Age-standardized prevalence, death, and DALYs were presented per 100,000 population with 95% uncertainty intervals (UI).
Findings
The prevalence for all metabolic diseases increased from 2000-2019, with the most pronounced increase in males and high SDI countries. In 2019, the highest age-standardised death rates were observed in hypertension (133·88 [121·25-155·73]; males, 160·13 [138·91-180·79]; females, 119·66 [102·33-136·86]), followed by obesity (62·59 [39·92-89·13]; males, 66·55 [39·76-97·21]; females, 58·14 [38·53-81·39]), hyperlipidemia (56·51 [41·83-73·62]; males, 67·33 [50·78-86·43]; females, 46·50 [32·70-62·38]), T2DM (18·49 [17·18-19·66]; males, 19·94 [18·50-21·32]; females, 17·30 [15·62-18·70]) and NAFLD (2·09 [1·61-2·60]; males, 2·38 [1·82-3·02]; females, 1·82 [1·41-2·27]). Similarly, obesity (1932·54 [1276·61-2639·74]) had the highest age-standardised DALYs, followed by hypertension (2885·57 [2580·75-3201·05]), hyperlipidemia (1207·15 [975·07-1461·11]), T2DM (801·55 [670·58-954·43]) and NAFLD (53·33 [40·73-68·29]). Mortality rates decreased over time in hyperlipidemia (-60%), hypertension (-47%), NAFLD (-31%) and T2DM (-20%), but not in obesity (107% increase). The highest metabolic-related mortality was observed in the Eastern Mediterranean and low SDI countries.
Conclusion
The growing prevalence of metabolic diseases, increasing obesity-related mortality trends, and the sex-regional-socioeconomic disparities evident in young adulthood, present the concerning global burden of metabolic diseases now and in the years ahead.
A cohort case–control study was conducted in XiangYa Hospital, Changsha, China, which involved 305 patients and 399 healthy women, from June 2010 to December 2018, to evaluate the association between Chinese women’s short- and long-term exposure to industrial air pollutant, SO 2 and gynaecological cancer (GC). We obtained personal and family information from the XiangYa Hospital electronic computer medical records. Using data obtained from the air quality monitoring stations in Changsha, we estimated each woman’s exposure to the industrial air pollutant, sulphur dioxide (SO 2 ), for different time windows, including the past 1, 5, 10 and 15 years before diagnosis of the disease. A multiple logistic regression model was used to assess the association between GC and SO 2 exposure. GC was significantly associated with long-term SO 2 exposure, with adjusted odds ratio (95% confidence interval) = 1.56 (1.10–2.21) and 1.81 (1.07–3.06) for a per interquartile range increase in the past 10 and 15 years, respectively. Sensitivity analysis showed that different groups reacted in different ways to long-term SO 2 exposure. We concluded that long-term exposure to high concentration of industrial pollutant, SO 2 is associated with the development of GC. This finding has implications for the prevention and reduction of GC.
Pregnant women may develop gestational diabetes mellitus (GDM), a disease of pregnancy characterised by maternal and fetal hyperglycaemia with hazardous consequences to the mother, the fetus, and the newborn. Maternal hyperglycaemia in GDM results in fetoplacental endothelial dysfunction. GDM-harmful effects result from chronic and short periods of hyperglycaemia. Thus, it is determinant to keep glycaemia within physiological ranges avoiding short but repetitive periods of hyper or hypoglycaemia. The variation of glycaemia over time is defined as ‘glycaemia dynamics’. The latter concept regards with a variety of mechanisms and environmental conditions leading to blood glucose handling. In this review we summarized the different metrics for glycaemia dynamics derived from quantitative, plane distribution, amplitude, score values, variability estimation, and time series analysis. The potential application of the derived metrics from self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) in the potential alterations of pregnancy outcome in GDM are discussed.
To support a mixture risk assessment with a focus on male reproductive health, we conducted a systematic review of associations between bisphenol A (BPA) exposures and declines in semen quality, based on animal and epidemiological studies. Contrary to a widely held view that there is “conflicting” evidence of such associations, our review and confidence rating approach reveals that animal studies provide convincing evidence of declines of semen quality after gestational BPA exposures. Many of the reported negative findings can be attributed to deficiencies in study sensitivity, insufficient control of background contamination and probable confounding through hormonal interference due to the use of soy-containing diets. We did not evaluate animal studies of adult BPA exposures. Divergent findings in “medium to high” and “medium” confidence epidemiological studies can be explained in terms of differences in exposure conditions. We attempted the estimation of a BPA reference dose based on animal studies. Due to variations in the no-observed adverse effect levels (NOAELs) in high confidence studies, possible reference doses ranged from 0.0001 to 0.0099 μg/kg/d. In choosing 0.003 μg/kg/d we struck a balance between caution suggested by studies at the lower end of the doses and the weight of evidence from studies with higher NOAELs. This weighting was motivated by the intended use of the value in a mixture risk assessment which meant arriving at a reasonable estimate of BPA exposures likely without effects on semen quality. We realise that our approach does not conform with the standards necessary for deriving tolerable daily intakes (TDIs) for single chemical exposures, which is not our interest here. BPA exposures currently experienced by European populations and beyond are in excess of 0.003 μg/kg/d and even fall in the range where some epidemiological studies observed effects on semen quality as a result of BPA exposures in adulthood.
Aims
Arsenic is a risk factor for type 2 diabetes and cardiovascular disease. However, little is known about arsenic effects over adipocyte endocrine functionality, particularly for leptin and adiponectin, and about its interaction with dietary components, which are the main environmental regulators of adipose tissue functionality. The aim of this work was to evaluate leptin and adiponectin in mature 3T3-L1 adipocytes exposed to palmitate (simulating excess fat intake), arsenic, or both throughout two different stages of adipogenesis.
Material and methods
3T3-L1 adipocytes were exposed starting from the beginning of its differentiation process during 11 d or once adipocytes were mature for 72 h. Adipokines secretion was evaluated by ELISA, intracellular protein levels and secreted adiponectin multimers by Western blot and mRNA abundance by qPCR.
Key findings
Leptin and adiponectin secretion decreased by arsenite alone or in combination with palmitate due to reduced gene and protein expression of both adipokines. However, leptin was impaired more at the transcriptional level, whereas affections to adiponectin were more relevant at the intracellular protein amount level with changes in the multimers proportion. The gene expression of several of their transcription factors was altered. Additionally, the magnitude of the effects depends on the adipocyte cell stage at which exposure began; adiponectin was more affected when exposure started from differentiation and leptin once adipocytes were mature.
Significance
These results in an in vivo model could be translated into less satiety and reduced insulin sensitivity.
Emerging evidence shows that the gut microbiota interacts with environmental pollutants, but the effect of early exposure on the neonatal microbiome remains unknown. We investigated the association between maternal exposure to environmental pollutants and changes in early-life gut microbiome development. We surveyed 16S rRNA gene on meconium and fecal samples (at 1, 3, and 6 months) from the Brazilian birth cohort, and associated with levels of metals, perfluoroalkyl chemicals (PFAS), and pesticides in maternal and umbilical cord blood. The results indicate that the magnitude of the microbiome changes associated with increasing pollutant exposure was bigger in cesarean-section (CS) born and CS-born-preterm babies, in relation to vaginally (VG) delivered infants. Breastfeeding was associated with a stronger pollutant-associated effect on the infant feces, suggesting that the exposure source could be maternal milk. Differences in microbiome effects associated with maternal or cord blood pollutant concentrations suggest that fetal exposure time - intrauterine or perinatal - may matter. Finally, despite the high developmental microbiota variability, specific microbionts were consistently affected across all pollutants, with taxa clusters found in samples from infants exposed to the highest toxicant exposure. The results evidence that perinatal exposure to environmental pollutants is associated with alterations in gut microbiome development which may have health significance.
Arsenic is found in soil, food, water and earth crust. Arsenic exposure is associated with chronic diseases such as cancer, cardiovascular disease as well as diabetes. One of complex effects of arsenic is on weight gain or loss. Involvement of arsenic in both weight loss and gain signaling pathways has previously been reported; however, too little attention has been paid to its weight reducing effect. Animal studies exhibited a role of arsenic in weight loss. In this regard, arsenic interference with endocrine system, leptin and adiponectin hormones as well as thermogenesis is more evidence. Apparently, arsenic-induced weight lossis generally meditated by its interaction with thermogenesis. In this review we have discussed the irregularities in metabolic pathways induced by arsenic that can lead to weight loss.
Exposome research aims to comprehensively understand the multiple environmental exposures that influence human health. To date, much of exposome science has focused on environmental chemical exposures and does not take a lifecourse approach. The rising prevalence of obesity, and the limited success in its prevention points to the need for a better understanding of the diverse exposures that associate with, or protect against, this condition, and the mechanisms driving its pathogenesis. The objectives of this review were to 1. evaluate the evidence on the maternal metabolic exposome in the programming of offspring growth/obesity and 2. identify and discuss the mechanisms underlying the programming of obesity. A systematic review was conducted following PRISMA guidelines to capture articles that investigated early life metabolic exposures and offspring weight and/or obesity outcomes. Scientific databases were searched using pre-determined indexed search terms, and risk of bias assessments were conducted to determine study quality. A final total of 76 articles were obtained and extracted data from human and animal studies were visualised using GOfER diagrams. Multiple early life exposures, including maternal obesity, diabetes and adverse nutrition, increase the risk of high weight at birth and postnatally, and excess adipose accumulation in human and animal offspring. The main mechanisms through which the metabolic exposome programmes offspring growth and obesity risk include epigenetic modifications, altered placental function, altered composition of the gut microbiome and breast milk, and metabolic inflammation, with downstream effects on development of the central appetite system, adipose tissues and liver. Understanding early life risks and protectors, and the mechanisms through which the exposome modifies health trajectories, is critical for developing and applying early interventions to prevent offspring obesity later in life.
Breast milk is a unique biological sample that reflects the exposure levels of both lactating mothers and infants. The exposure levels of BPA due to breast milk consumption for infants can be estimated easily, but the method to estimate the total daily intake (TDI) of lactating mothers from breast milk has not yet been established. In this study, BPA concentrations were detected in breast milk samples from 149 lactating mothers from Hunan, China. The median concentration of BPA in breast milk was 0.053 μg/L with a range of 0.001–2.535 μg/L, and a temporal decline trend was found for BPA concentrations in breast milk (p < 0.05). The median intake of BPA via breast milk was 26.8 ng/kg bw/day for 0-3-month-old infants and 7.0 ng/kg bw/day for 4-12-month-old infants. Based on the predicted concentrations of BPA in urine and blood via the conversion coefficients from breast milk, the TDIs of lactating mothers were estimated. The TDIs estimated from the simulated urine concentration were 84.0 ± 175.2 ng/kg bw/day for 0-3-month-old infants' mothers and 36.9 ± 80.8 ng/kg bw/day for 4-12-month-old infants' mothers. The dietary daily intakes estimated from the simulated blood concentration were 579.6 ± 370.8 ng/kg bw/day for 0-3-month-old infants' mothers and 280.1 ± 195.2 ng/kg bw/day for 4-12-month-old infants’ mothers. When assuming the dietary daily intakes in Hunan of the fifth total diet study (TDS) as the “true” total dietary intake of our population, the contribution of diet was estimated to be 63.7%, which suggested that non-dietary BPA exposure may be underestimated.
Background and aim
A large number of chemical compounds with endocrine-disrupting activity have been documented. These chemicals are ubiquitous and widely used in many products of our daily lives. Bisphenol A (BPA) is among the most common Endocrine Disrupting Chemical (EDC) that has been used for many years in the manufacture of polycarbonate plastics and epoxy resins. There is growing evidence that exposure to these EDCs poses a possible health risk. This review focuses on the effect of EDCs, in particular, BPA on female reproduction and Polycystic Ovary Syndrome (PCOS), which is the most prevalent endocrine disorder of reproductively aged women.
Methods
A relevant literature survey was conducted with Google scholar and Pubmed using several appropriate keywords to select the most relevant studies evaluating the role of endocrine disrupting-chemicals in female reproduction.
Results
The female menstrual cycle and fertility are very sensitive to hormonal imbalance and alteration in endocrine function during critical times and different stages of lifecycle owing to EDC exposure results in many abnormalities like menstrual irregularities, impaired fertility, PCOS, and Endometriosis among others. BPA is the most extensively studied EDC worldwide and has been strongly associated with female reproductive health.
Conclusion
EDCs lead to deleterious effects on human health including reproductive health which are of global concern. Exposure to EDCs in early life can elicit disease in adult life and maybe even transgenerational. There is an immediate need to minimize the ill effect of EDCs which can be tackled through the collection of more data to clarify the clinical implications of EDCs.
Objectives
Birth weight is an important public health indicator that reflects fetal health conditions and predicts future health. Identifying the most important factors related to birth weight would help defining preventive health strategies for both mothers and children. The objectives of this study are i. to describe, using a large birth database from a Chilean hospital, the trend of birth weight during 2002–2015, and ii. to determine factors during prenatal care associated with low and high birth weight.
Study design
This study is a secondary analysis of all single birth records at a Chilean Hospital in the southeast district of Santiago, Chile, during 2002–2015 (N = 78,931).
Methods
Sociodemographic information, clinical and obstetric history, lifestyle, and anthropometric variables were evaluated as potential predictors. Birth weight was categorized into five groups as per percentiles of weight as per gestational age. Data were extracted from clinical records. We used classification and regression tree methodology and logistic regression.
Results
The average birth weight for the period was 3316 g (SD 566), with little variation across time. Preterm births increased from 7% in 2002 to 10% in 2015, and births >40 weeks decreased from 10.7% in 2002 to 4.4% in 2015. The percentages of small and large for gestational age changed from 10.9% and 12.7% in 2002 to 9.9% and 13.9% in 2015, respectively. The predictors included in the optimal tree were body mass index, gestational weight gain, pre-eclampsia, and gestational diabetes. We found that women with a pregestational body mass index <28 kg/m², gestational weight gain <17 kg, and preeclampsia had a probability of 41% of having a small for gestational age neonate. Conversely, women with a body mass index ≥28 kg/m², gestational weight gain ≥17 kg, and gestational diabetes had a probability of 44% of having a large for gestational age neonate.
Conclusions
This study showed that the most important variables explaining birth weight are those related to maternal nutritional status. Thus, the strategies to promote a normal birth weight should aim for a normal maternal weight at the beginning of pregnancy, gestational weight gain within the recommendations, and prevention of gestational diabetes and pre-eclampsia.
The aim of CONTAMILK study was to estimate levels of contamination of breast milk (BM) of Moroccan nursing mothers by some xenobiotics including, lead (Pb), to identify associated factors of exposure and to determine the daily intake of newborns. Lead concentrations were determined in 70 samples of colostrum by ICPMS and a structured questionnaire was filled during milk collection to report participants’ data. The median lead concentration was 9,08 µg/L (range 1.38 – 515,39 µg/L) and in 79% of samples, levels were higher than the normal range reported by the World Health Organization (WHO) in BM (2-5 μg/L). Indeed, preterm delivery, frequency of use of cosmetic powders and lipsticks were significantly associated with the level of lead in BM. The estimated daily intake was greater than the tolerable daily intake (TDI) of the European food safety authority (0.5 µg/kg/day) for 39 babies and 6 babies according to the WHO (3.6 µg/kg/day).
A liquid chromatography-tandem mass spectrometry analytical method was developed for the simultaneous determination of five parabens and four bisphenols in human breast milk samples in both free forms and as the total concentration, which included also conjugated compounds. The samples for the determination of free forms were extracted directly using the QuEChERS method, while the determination of the total content included a preliminary enzymatic hydrolysis step. Breast milk was sampled 3-6 weeks and 3 months after delivery. Methylparaben was the most abundant paraben with an average total concentration in the two sampling points 1.02 and 1.52 ng mL⁻¹, respectively. Bisphenol A was the most abundant bisphenol with an average total concentration in the two sampling points 1.91 and 1.41 ng mL⁻¹, respectively. For the first time, the hazard quotients were calculated for these compounds in the breast milk samples demonstrating that bisphenol A contributed the most to the hazard caused by the tested compounds. However, the hazard index calculated for the cumulative impact indicates that the milk samples were safe for the children.