Variation in Stability of Endogenous Reference Genes in Fallopian Tubes and Endometrium from Healthy and Ectopic Pregnant Women

RT-qPCR is commonly employed in gene expression studies in ectopic pregnancy. Most use RN18S1, β-actin or GAPDH as internal controls without validation of their suitability as reference genes. A systematic study of the suitability of endogenous reference genes for gene expression studies in ectopic pregnancy is lacking. The aims of this study were therefore to evaluate the stability of 12 reference genes and suggest those that are stable for use as internal control genes in fallopian tubes and endometrium from ectopic pregnancy and healthy non-pregnant controls. Analysis of the results showed that the genes consistently ranked in the top six by geNorm and NormFinder algorithms, were UBC, GAPDH, CYC1 and EIF4A2 (fallopian tubes) and UBC and ATP5B (endometrium). mRNA expression of NAPE-PLD as a test gene of interest varied between the groups depending on which of the 12 reference genes was used as internal controls. This study demonstrates that arbitrary selection of reference genes for normalisation in RT-qPCR studies in ectopic pregnancy without validation, risk producing inaccurate data and should therefore be discouraged

Children’s Environmental Health in Thailand: Past, Present, and Future

Background: There is increasing evidence of a link between environmental pollution and preventable diseases in developing countries, including Thailand. Economic development has generated several types of pollution that can affect population health. While these environmental health effects can be observed throughout life, pregnant women and children represent particularly vulnerable and sensitive groups. Methods: The published epidemiological literature investigating environmental chemical exposure in Thai children was reviewed, highlighting those that investigated associations between exposure and subsequent health outcomes. Results: The majority of the Thai epidemiological studies on environmental health in children were cross-sectional in design, with some demonstrating associations between exposure and outcome. The three main types of chemical exposure in Thai children were pesticides, heavy metals, and air pollution, which resulted from agricultural activities in countryside areas, industrial zones (both registered and unregistered establishments), mining, and traffic in inner cities. Major health outcomes included detrimental effects on cognitive function and cancer risk. Pesticide exposure was focused on, but not limited to, agricultural areas. The success of the Thai environmental policy to introduce lead–free petrol can be demonstrated by the decline of mean blood lead levels in children, particularly in urban areas. However, unregistered lead-related factories and smelters act as hidden sources. In addition, there is increasing concern, but little acknowledgement, about the effects of chronic arsenic exposure related to mining. Lastly, air pollution remains a problem in both dense city populations due to traffic and in rural areas due to contamination of indoor air and house dust with heavy metals, endotoxins and other allergens. Conclusions: The increasing number of published articles demonstrates an improved awareness of children’s environmental health in Thailand. Chemical hazards, including the improper use of pesticides, environmental contamination with heavy metals (lead and arsenic), and air pollution in inner cities and indoor air, continue to be growing issues

Doxorubicin In Vivo Rapidly Alters Expression and Translation of Myocardial Electron Transport Chain Genes, Leads to ATP Loss and Caspase 3 Activation

BackgroundDoxorubicin is one of the most effective anti-cancer drugs but its use is limited by cumulative cardiotoxicity that restricts lifetime dose. Redox damage is one of the most accepted mechanisms of toxicity, but not fully substantiated. Moreover doxorubicin is not an efficient redox cycling compound due to its low redox potential. Here we used genomic and chemical systems approaches in vivo to investigate the mechanisms of doxorubicin cardiotoxicity, and specifically test the hypothesis of redox cycling mediated cardiotoxicity.Methodology/principal findingsMice were treated with an acute dose of either doxorubicin (DOX) (15 mg/kg) or 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) (25 mg/kg). DMNQ is a more efficient redox cycling agent than DOX but unlike DOX has limited ability to inhibit gene transcription and DNA replication. This allowed specific testing of the redox hypothesis for cardiotoxicity. An acute dose was used to avoid pathophysiological effects in the genomic analysis. However similar data were obtained with a chronic model, but are not specifically presented. All data are deposited in the Gene Expression Omnibus (GEO). Pathway and biochemical analysis of cardiac global gene transcription and mRNA translation data derived at time points from 5 min after an acute exposure in vivo showed a pronounced effect on electron transport chain activity. This led to loss of ATP, increased AMPK expression, mitochondrial genome amplification and activation of caspase 3. No data gathered with either compound indicated general redox damage, though site specific redox damage in mitochondria cannot be entirely discounted.Conclusions/significanceThese data indicate the major mechanism of doxorubicin cardiotoxicity is via damage or inhibition of the electron transport chain and not general redox stress. There is a rapid response at transcriptional and translational level of many of the genes coding for proteins of the electron transport chain complexes. Still though ATP loss occurs with activation caspase 3 and these events probably account for the heart damage

Air quality and mental health: evidence, challenges and future directions

Background: Poor air quality is associated with poor health. Little attention is given to the complex array of environmental exposures and air pollutants that affect mental health during the life course. // Aims: We gather interdisciplinary expertise and knowledge across the air pollution and mental health fields. We seek to propose future research priorities and how to address them. // Method: Through a rapid narrative review, we summarise the key scientific findings, knowledge gaps and methodological challenges. // Results: There is emerging evidence of associations between poor air quality, both indoors and outdoors, and poor mental health more generally, as well as specific mental disorders. Furthermore, pre-existing long-term conditions appear to deteriorate, requiring more healthcare. Evidence of critical periods for exposure among children and adolescents highlights the need for more longitudinal data as the basis of early preventive actions and policies. Particulate matter, including bioaerosols, are implicated, but form part of a complex exposome influenced by geography, deprivation, socioeconomic conditions and biological and individual vulnerabilities. Critical knowledge gaps need to be addressed to design interventions for mitigation and prevention, reflecting ever-changing sources of air pollution. The evidence base can inform and motivate multi-sector and interdisciplinary efforts of researchers, practitioners, policy makers, industry, community groups and campaigners to take informed action. // Conclusions: There are knowledge gaps and a need for more research, for example, around bioaerosols exposure, indoor and outdoor pollution, urban design and impact on mental health over the life course

Air quality and mental health: evidence, challenges and future directions

Background: Poor air quality is associated with poor health. Little attention is given to the complex array of environmental exposures and air pollutants that affect mental health during the life course. Aims: We gather interdisciplinary expertise and knowledge across the air pollution and mental health fields. We seek to propose future research priorities and how to address them. Method: Through a rapid narrative review, we summarise the key scientific findings, knowledge gaps and methodological challenges. Results: There is emerging evidence of associations between poor air quality, both indoors and outdoors, and poor mental health more generally, as well as specific mental disorders. Furthermore, pre-existing long-term conditions appear to deteriorate, requiring more healthcare. Evidence of critical periods for exposure among children and adolescents highlights the need for more longitudinal data as the basis of early preventive actions and policies. Particulate matter, including bioaerosols, are implicated, but form part of a complex exposome influenced by geography, deprivation, socioeconomic conditions and biological and individual vulnerabilities. Critical knowledge gaps need to be addressed to design interventions for mitigation and prevention, reflecting ever-changing sources of air pollution. The evidence base can inform and motivate multi-sector and interdisciplinary efforts of researchers, practitioners, policy makers, industry, community groups and campaigners to take informed action. Conclusions: There are knowledge gaps and a need for more research, for example, around bioaerosols exposure, indoor and outdoor pollution, urban design and impact on mental health over the life course.Natural Environment Research Council (NERC): NE/V002171/1; Engineering and Physical Sciences Research Council (EPSRC): EP/V052462/1; EP/W001411/1; EP/T003189/

Targeting of the Arpc3 actin nucleation factor by miR-29a/b regulates dendritic spine morphology

Regulation of Arpc3 by miRNA alters dendritic spine morphology

Environmentally induced epigenetic toxicity: potential public health concerns

<p>Throughout our lives, epigenetic processes shape our development and enable us to adapt to a constantly changing environment. Identifying and understanding environmentally induced epigenetic change(s) that may lead to adverse outcomes is vital for protecting public health. This review, therefore, examines the present understanding of epigenetic mechanisms involved in the mammalian life cycle, evaluates the current evidence for environmentally induced epigenetic toxicity in human cohorts and rodent models and highlights the research considerations and implications of this emerging knowledge for public health and regulatory toxicology. Many hundreds of studies have investigated such toxicity, yet relatively few have demonstrated a mechanistic association among specific environmental exposures, epigenetic changes and adverse health outcomes in human epidemiological cohorts and/or rodent models. While this small body of evidence is largely composed of exploratory <i>in vivo</i> high-dose range studies, it does set a precedent for the existence of environmentally induced epigenetic toxicity. Consequently, there is worldwide recognition of this phenomenon, and discussion on how to both guide further scientific research towards a greater mechanistic understanding of environmentally induced epigenetic toxicity in humans, and translate relevant research outcomes into appropriate regulatory policies for effective public health protection.</p