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Mutation Research. Reviews in Mutation... 2020Cleft lip and palate (CL/P) is among the most common congenital malformations and affects 1 in 700 newborns. CL/P is caused by genetic and environmental factors...
UNLABELLED
Cleft lip and palate (CL/P) is among the most common congenital malformations and affects 1 in 700 newborns. CL/P is caused by genetic and environmental factors (maternal smoking, alcohol or drug use and others). Many genes and loci were associated with cleft lip/palate but the amount of heterogeneity justifies identifying new causal genes and variants. AHRR (Aryl-Hydrocarbon Receptor Repressor) gene has recently been related to CL/P however, few functional studies analyze the genotypephenotype interaction of AHRR with CL/P. Several studies associate the molecular pathway of AHRR to CL/P which indicates this gene as a functional candidate in CL/P etiology.
METHODS
Systematic Literature Review was performed using PUBMED database with the keywords cleft lip, cleft palate, orofacial cleft, AHRR and synonyms. SLR resulted in 37 included articles.
RESULTS
AHRR is a positional and functional candidate gene for CL/P. In silico analysis detected interactions with other genes previously associated to CL/P like ARNT and CYP1A1. AHRR protein regulates cellular toxicity through TCDD mediated AHR pathway. Exposure to TCDD in animal embryos is AHR mediated and lead to cleft palate due to palate fusion failure and post fusion rupture. AHRR regulates cellular growth and differentiation, fundamental to lip and palatogenesis. AHRR decreases carcinogenesis and recently a higher tumor risk has been described in CL/P patients and families. AHRR is also a smoking biomarker due to changed methylation sites found in smokers DNA although folate intake may partially revert these methylation alterations. This corroborates the role of maternal smoking and lack of folate supplementation as risk factors for CL/P.
CONCLUSION
This research identified the importance of AHRR in dioxin response and demonstrated an example of genetic and environmental interaction, indispensable in the development of many complex diseases.
Topics: Amino Acid Motifs; Basic Helix-Loop-Helix Transcription Factors; Biomarkers; Cleft Lip; Cleft Palate; DNA Methylation; Dietary Supplements; Female; Folic Acid; Genetic Association Studies; Humans; Infant, Newborn; Male; Models, Molecular; Protein Domains; RNA Isoforms; Repressor Proteins; Risk Factors; Smoking
PubMed: 32800270
DOI: 10.1016/j.mrrev.2020.108319 -
Environmental Research Jun 2019ADHD is a common neurodevelopmental disorder highly attributed to genetics, but the combination of other social and environmental determinants, as well as potential...
ADHD is a common neurodevelopmental disorder highly attributed to genetics, but the combination of other social and environmental determinants, as well as potential gene-environment interactions, can also be responsible. This paper aims to review relevant literature published up to April 2018 for determining whether air pollution caused by ambient gaseous (NO, SO, PCDD/Fs, Benzene) and particulate matters (PM, PM, PM, PAH, BC/EC) as an environmental risk factor is associated with increased risk of ADHD in children. Relevant literature was identified through electronic searches of PubMed, Embase, Web of Science, Scopus database and gray literature. A total of 872 articles were initially identified 28 of which meeting the defined inclusion criteria were included. The methodological quality of the included articles was evaluated using the modified Critical Appraisal Skills Programs (CASP) and confounding variables, exposure and outcome measurement were assessed. The results of this systematic review revealed that there is more evidence on the detrimental effects of EC, BC, and PM on ADHD compared to PAH. Among gaseous air pollutants, association was found between SO and urinary level of t,t-MA (trans, trans-muconic acid) as a proxy-biomarker of NO exposure, not merely benzene. However few studies related to NO (0.46%) found detrimental effects. Overall, the number of studies reporting an association between air pollution and increased risk of ADHD is relatively higher compared to the number of studies reporting no association. However, the findings of the studies provided limited evidence to support the idea that exposure to air pollution may be linked to increased risk of ADHD. Well-designed and harmonized studies considering standard methods for individual exposure assessment, critical windows of susceptibility, and appropriate tools for outcome measurement, can improve the quality of epidemiological studies and strengthen the evidence. Since ADHD with its long-term consequences can impose large costs to communities and impact the children performance, determination of the risk factors in children and particularly the role of the environment as priorities for research should be considered.
Topics: Air Pollutants; Air Pollution; Attention Deficit Disorder with Hyperactivity; Child; Dibenzofurans; Environmental Exposure; Gases; Humans; Particulate Matter; Polychlorinated Dibenzodioxins
PubMed: 30909100
DOI: 10.1016/j.envres.2019.03.030 -
Critical Reviews in Oncology/hematology Dec 2015During the past three decades, large areas of the Naples and the Caserta provinces of the Campania region in Italy have been extensively contaminated by the widespread... (Review)
Review
During the past three decades, large areas of the Naples and the Caserta provinces of the Campania region in Italy have been extensively contaminated by the widespread burial and open-air dumping and incineration of industrial toxic waste. On the basis of the finding that the incidence of bladder cancer appears remarkably high in the Naples province with respect to the rest of Europe and of a potential causative role of environmental contaminants, we sought associations between exposure to toxic agents and increased mortality/incidence of bladder cancer by performing a systematic search of epidemiology and human biomonitoring studies conducted in the provinces of Naples and Caserta. The data show that the incidence of bladder cancer is higher than expected on the basis of regional data in the province of Naples and in certain areas of the province of Caserta, even after accounting for social deprivation, with two clusters of increased mortality rate located in the north-western part of Naples province and in the south-eastern part of the Caserta province. The biomonitoring studies conducted focused on the levels of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs), which are generated by the uncontrolled combustion of refuse abandoned in the territory and have been shown to enter the food chain. While the average values of PCDD/F and PCBs reported in blood serum and human milk of the area population are in accordance with those expected on the basis of studies conducted at a national and international level, five municipalities assessed in the province of Naples, that is Brusciano, Caivano, Giugliano, Mugnano, and Qualiano-Villaricca were clearly characterized by the presence of arsenic, with 62% samples showing serum arsenic levels higher than the 95th percentile of the national distribution. The potential negative synergism of social deprivation, environmental pressure and arsenic contamination may account for the higher than expected bladder cancer incidence and mortality in certain areas of the Campania region and remains to be elucidated via the conduction of ad hoc population-based studies.
Topics: Environmental Monitoring; Environmental Pollutants; Humans; Italy; Risk Factors; Urinary Bladder Neoplasms
PubMed: 26520458
DOI: 10.1016/j.critrevonc.2015.07.004 -
Toxicological Sciences : An Official... Jan 2021Regulatory agencies have derived noncancer toxicity values for 2,3,7,8-tetrachlorodibenzo-p-dioxin based on reduced sperm counts relying on single studies from a large...
Development of a Range of Plausible Noncancer Toxicity Values for 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Based on Effects on Sperm Count: Application of Systematic Review Methods and Quantitative Integration of Dose Response Using Meta-Regression.
Regulatory agencies have derived noncancer toxicity values for 2,3,7,8-tetrachlorodibenzo-p-dioxin based on reduced sperm counts relying on single studies from a large body of evidence. Techniques such as meta-regression allow for greater use of the available data while simultaneously providing important information regarding the uncertainty associated with the underlying evidence base when conducting risk assessments. The objective herein was to apply systematic review methods and meta-regression to characterize the dose-response relationship of gestational exposure and epididymal sperm count. Twenty-three publications (20 animal studies consisting of 29 separate rat experimental data sets, and 3 epidemiology studies) met inclusion criteria. Risk of bias evaluation was performed to critically appraise study validity. Low to very low confidence precluded use of available epidemiological data as candidate studies for dose-response due to inconsistencies across the evidence base, high risk of bias, and general lack of biological coherence, including lack of clinical relevance and dose-response concordance. Experimental animal studies, which were found to have higher confidence following the structured assessment of confidence (eg, controlled exposure, biological consistency), were used as the basis of a meta-regression. Multiple models were fit; points of departure were identified and converted to human equivalent doses. The resulting reference dose estimates ranged from approximately 4 to 70 pg/kg/day, depending on model, benchmark response level, and study validity integration approach. This range of reference doses can be used either qualitatively or quantitatively to enhance understanding of human health risk estimates for dioxin-like compounds.
Topics: Animals; Male; Rats; Benchmarking; Dioxins; Dose-Response Relationship, Drug; Epididymis; Polychlorinated Dibenzodioxins; Spermatozoa
PubMed: 33306106
DOI: 10.1093/toxsci/kfaa171 -
Journal of Hazardous Materials Mar 2024COVID-19 has aggravated the biomedical waste generation all over the world and the concern for its safe disposal is on the rise. The vast majority of healthcare systems... (Review)
Review
COVID-19 has aggravated the biomedical waste generation all over the world and the concern for its safe disposal is on the rise. The vast majority of healthcare systems employ incineration as their treatment method considering its agility to reduce the waste volume by up to 95-96% and high-temperature inactivation of infectious biological materials. However, incinerator emission is a significant contributor of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (dl-PCBs) according to various national inventories across the globe. Bio-Medical Waste Incinerators (BMWIs) are the dominant form of incinerator plants in developing nations and hence BMWI emissions were found to contribute lion's share of national dioxins inventories in most of these countries. The Stockholm Convention on POPs played a key role in imbibing significant urge on the dl-POPs monitoring studies of incinerators internationally and on controlling the average incinerator emission levels. Though many national/international agencies endorse a stringent incinerator stack emission standard of 0.1 ngTEQ/Nm, there are some differences observed in nation-to-nation regulatory scenarios. This paper reviews and reports on the dioxins emission and health risk studies associated with bio-medical waste incineration over the last three decades (1990-2020) with a comprehensive spatial and temporal emission trend analysis. An overview of important national and international regulations, national inventories and emission factors for the biomedical waste incineration sector is also reviewed in detail. The study observes that continuous regulatory monitoring and logical relaxations can enhance the performance of the existing facilities ensuring low emissions and minimal risk.
Topics: Dioxins; Air Pollutants; Environmental Monitoring; Incineration; Polychlorinated Dibenzodioxins; Polychlorinated Biphenyls; Dibenzofurans, Polychlorinated
PubMed: 38176262
DOI: 10.1016/j.jhazmat.2023.133384 -
Frontiers in Endocrinology 20212,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a well-known environmental poison that exist in the environment for many years. However, its effect on the male... (Meta-Analysis)
Meta-Analysis
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a well-known environmental poison that exist in the environment for many years. However, its effect on the male reproductive system has not been clearly stated. We conducted a meta-analysis of the effect of TCDD on the male reproductive system of rodents about TCDD. Results showed that that TCDD exposure reduced the testis weight (weighted mean difference [WMD]: -0.035, 95% confidence interval [CI]: -0.046 to -0.025), sperm count (WMD: -35, 95% CI: -42.980 to -27.019), and blood testosterone concentration (WMD: -0.171, 95% CI: -0.269 to -0.073). According to our research results, TCDD can cause damage to the male reproductive system of rodents through direct or indirect exposure. In order to further explore the potential hazards of TCDD to humans, more human-related research needs to be carried out.
Topics: Animals; Data Analysis; Environmental Pollutants; Genitalia, Male; Humans; Male; Men's Health; Models, Animal; Polychlorinated Dibenzodioxins; Rodentia; Semen Analysis; Toxicity Tests
PubMed: 34803904
DOI: 10.3389/fendo.2021.696106 -
Critical Reviews in Toxicology Jul 2019Solid waste incinerators (SWI) emit several pollutants among which polychlorodibenzodioxins and furans (PCDD/Fs), polychlorobiphenyls, metals, monocyclic and polycyclic...
Solid waste incinerators (SWI) emit several pollutants among which polychlorodibenzodioxins and furans (PCDD/Fs), polychlorobiphenyls, metals, monocyclic and polycyclic aromatic hydrocarbons (PAHs). To present a systematic review of peer-reviewed literature on human biological monitoring of exposure and effect following potential exposure to SWI pollutants to bring together evidences and to highlight strengths and deficiencies of the studies conducted so far. Relevant studies on biomonitoring of individuals living near or working at SWIs were selected through three steps: (1) a literature search in the Medline, CAplus, and Embase database; (2) the retrieved abstracts were screened by four independent reviewers; (3) the full text of the relevant papers was read, papers were pooled in studies, and then analyzed to highlight strengths and weaknesses. Studies with the strongest epidemiological design and/or the largest sample size were identified as reference studies. One hundred and thirty-two papers, pooled in 82 studies, were included in the review: 67 on general population, 52 on SWI workers, and 14 on both groups. The most frequently investigated biomarkers were PCDD/Fs in plasma (87). Several studies presented limitations, such as a small samples size, scarce information on confounders, and a poor statistical analysis. Some earlier studies showed an increase of PCDD/Fs, lead, and PAHs in individuals (mainly workers) exposed to emissions from old SWIs; studies from the year 2000 showed no increase of biomarkers or biomarkers within the range of the general population; decreasing trends were observed in prospective studies. Most studies presented methodological pitfalls; reference studies showed no or a limited evidence of the impact of SWI on exposure and effect biomarkers.
Topics: Biological Monitoring; Dibenzofurans; Environmental Exposure; Environmental Pollutants; Humans; Incineration; Polychlorinated Dibenzodioxins; Polycyclic Aromatic Hydrocarbons; Solid Waste
PubMed: 31524034
DOI: 10.1080/10408444.2019.1630362 -
Environmental Science & Technology Jun 2021Large quantities of mismanaged plastic waste threaten the health and wellbeing of billions worldwide, particularly in low- and middle-income countries where waste...
Large quantities of mismanaged plastic waste threaten the health and wellbeing of billions worldwide, particularly in low- and middle-income countries where waste management capacity is being outstripped by increasing levels of consumption and plastic waste generation. One of the main self-management strategies adopted by 2 billion people who have no waste collection service, is to burn their discarded plastic in open, uncontrolled fires. While this strategy provides many benefits, including mass and volume reduction, it is a form of plastic pollution that results in the release of chemical substances and particles that may pose serious risks to public health and the environment. We followed adapted PRISMA guidelines to select and review 20 publications that provide evidence on potential harm to human health from open burning plastic waste, arranging evidence into eight groups of substance emissions: brominated flame retardants; phthalates; potentially toxic elements; dioxins and related compounds; bisphenol A; particulate matter; and polycyclic aromatic hydrocarbons. We semiquantitatively assessed 18 hazard-pathway-receptor combination scenarios to provide an indication of the relative harm of these emissions so that they could be ranked, compared and considered in future research agenda. This assessment overwhelmingly indicated a high risk of harm to waste pickers, a large group of 11 million informal entrepreneurs who work closely with waste, delivering a circular economy but often without protective equipment or a structured, safe system of work. Though the risk to human health from open burning emissions is high, this remains a substantially under-researched topic.
Topics: Flame Retardants; Humans; Plastics; Public Health; Recycling; Refuse Disposal
PubMed: 34003007
DOI: 10.1021/acs.est.0c08536 -
Environmental Toxicology and Chemistry Oct 2023The aryl hydrocarbon receptors (Ahrs) are evolutionarily conserved ligand-dependent transcription factors that are activated by structurally diverse endogenous compounds...
The aryl hydrocarbon receptors (Ahrs) are evolutionarily conserved ligand-dependent transcription factors that are activated by structurally diverse endogenous compounds as well as environmental chemicals such as polycyclic aromatic hydrocarbons and halogenated aromatic hydrocarbons. Activation of the Ahr leads to several transcriptional changes that can cause developmental toxicity resulting in mortality. Evidence was assembled and evaluated for two novel adverse outcome pathways (AOPs) which describe how Ahr activation (molecular initiating event) can lead to early-life stage mortality (adverse outcome), via either SOX9-mediated craniofacial malformations (AOP 455) or cardiovascular toxicity (AOP 456). Using a key event relationship (KER)-by-KER approach, we collected evidence using both a narrative search and a systematic review based on detailed search terms. Weight of evidence for each KER was assessed to inform overall confidence of the AOPs. The AOPs link to previous descriptions of Ahr activation and connect them to two novel key events (KEs), increase in slincR expression, a newly characterized long noncoding RNA with regulatory functions, and suppression of SOX9, a critical transcription factor implicated in chondrogenesis and cardiac development. In general, confidence levels for KERs ranged between medium and strong, with few inconsistencies, as well as several opportunities for future research identified. While the majority of KEs have only been demonstrated in zebrafish with 2,3,7,8-tetrachlorodibenzo-p-dioxin as an Ahr activator, evidence suggests that the two AOPs likely apply to most vertebrates and many Ahr-activating chemicals. Addition of the AOPs into the AOP-Wiki (https://aopwiki.org/) helps expand the growing Ahr-related AOP network to 19 individual AOPs, of which six are endorsed or in progress and the remaining 13 relatively underdeveloped. Environ Toxicol Chem 2023;42:2063-2077. © 2023 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Topics: Animals; Humans; Zebrafish; Receptors, Aryl Hydrocarbon; Polychlorinated Dibenzodioxins; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic
PubMed: 37341548
DOI: 10.1002/etc.5699 -
Marine Drugs Jun 2019The marine biosphere is a treasure trove of natural bioactive secondary metabolites and the richest source of structurally diverse and unique compounds, such as...
The marine biosphere is a treasure trove of natural bioactive secondary metabolites and the richest source of structurally diverse and unique compounds, such as phlorotannins and halo-compounds, with high therapeutic potential. Eckol is a precursor compound representing the dibenzo-1,4-dioxin class of phlorotannins abundant in the species, which are marine brown algae having a ubiquitous distribution. In search of compounds having biological activity from macro algae during the past three decades, this particular compound has attracted massive attention for its multiple therapeutic properties and health benefits. Although several varieties of marine algae, seaweed, and phlorotannins have already been well scrutinized, eckol deserves a place of its own because of the therapeutic properties it possesses. The relevant information about this particular compound has not yet been collected in one place; therefore, this review focuses on its biological applications, including its potential health benefits and possible applications to restrain diseases leading to good health. The facts compiled in this review could contribute to novel insights into the functions of eckol and potentially enable its use in different uninvestigated fields.
Topics: Animals; Antioxidants; Biological Factors; Dioxins; Humans; Phaeophyceae; Seaweed
PubMed: 31216636
DOI: 10.3390/md17060361