A Mixture of Endocrine Disrupting Chemicals Associated with Lower Birth Weight in Children Induces Adipogenesis and DNA Methylation Changes in Human Mesenchymal Stem Cells.

Endocrine Disrupting Chemicals (EDCs) are man-made compounds that alter functions of the endocrine system. Environmental mixtures of EDCs might have adverse effects on human health, even though their individual concentrations are below regulatory levels of concerns. However, studies identifying and experimentally testing adverse effects of real-life mixtures are scarce.

From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures.

Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence.

High antibody levels against human herpesvirus-6A interact with lifestyle factors in multiple sclerosis development.

Background: Infection with human herpesvirus 6A (HHV-6A) has been suggested to increase multiple sclerosis (MS) risk. However, potential interactions between HHV-6A and environmental/lifestyle risk factors for MS have not previously been studied.

Methods: We used two Swedish population-based case-control studies comprising 5993 cases and 5995 controls.

Bisphenol A Inhibits the Transporter Function of the Blood-Brain Barrier by Directly Interacting with the ABC Transporter Breast Cancer Resistance Protein (BCRP).

The breast cancer resistance protein (BCRP) is an important efflux transporter in the blood-brain barrier (BBB), protecting the brain from a wide range of substances. In this study, we investigated if BCRP function is affected by bisphenol A (BPA), a high production volume chemical used in common consumer products, as well as by bisphenol F (BPF) and bisphenol S (BPS), which are used to substitute BPA. We employed a transwell-based in vitro cell model of iPSC-derived brain microvascular endothelial cells, where BCRP function was assessed by measuring the intracellular accumulation of its substrate Hoechst 33342.

DNA methylation at GRIN2B partially mediates the association between prenatal bisphenol F exposure and cognitive functions in 7-year-old children in the SELMA study.

Background: Accumulating evidence suggests that prenatal chemical exposure triggers epigenetic modifications that could influence health outcomes later in life. In this study, we investigated whether DNA methylation (DNAm) levels at the glutamate ionotropic receptor NMDA type subunit 2B (GRIN2B) gene underlies the association between prenatal exposure to an endocrine disrupting chemical (EDC), bisphenol F (BPF), and lower cognitive functions in 7-year-old children.

Methods: Data from 799 children participating in the Swedish Environmental Longitudinal Mother and child Asthma and allergy (SELMA) pregnancy cohort was analyzed.

Prenatal exposure to bisphenols and cognitive function in children at 7 years of age in the Swedish SELMA study.

Background: Experimental evidence demonstrates that exposure to bisphenol A (BPA), and the recently introduced alternatives bisphenol S (BPS) and bisphenol F (BPF) alter normal neurodevelopment. More research is needed to evaluate the associations between exposure to individual BPA alternatives and neurodevelopmental outcomes in humans.

Objective: The present study aimed at examining the individual associations between prenatal BPA, BPS and BPF exposure and cognitive outcomes in children at age 7 years.

Childhood adversity increases methylation in the GRIN2B gene.

Childhood adversity is an early life stressor associated with increased risk of several psychiatric disorders such as depression. Epigenetic changes, primarily DNA methylation, can be affected by early life stress, which in turn might contribute to altered disease susceptibility later in life. One plausible biomarker of early life stress is methylation of the ionotropic glutamate receptor NMDA type subunit 2B (GRIN2B) gene, which has been previously shown to be epigenetically affected by prenatal environmental stressors.

Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis.

Human herpesvirus (HHV)-6A or HHV-6B involvement in multiple sclerosis (MS) etiology has remained controversial mainly due to the lack of serological methods that can distinguish the two viruses. A novel multiplex serological assay measuring IgG reactivity against the immediate-early protein 1 from HHV-6A (IE1A) and HHV-6B (IE1B) was used in a MS cohort (8,742 persons with MS and 7,215 matched controls), and a pre-MS cohort (478 individuals and 476 matched controls) to investigate this further. The IgG response against IE1A was positively associated with MS (OR = 1.

The effect of human herpesvirus 6B infection on the MAPK pathway.

Background: Human herpesvirus 6B (HHV-6B) is a neurotropic virus that has been repeatedly associated with mesial temporal lobe epilepsy (MTLE). However, the mechanism behind this suggested association is not known. Therefore, the aim of this study was to investigate what genes were affected by HHV-6B, possibly revealing HHV-6B induced disease causing mechanisms.

Human Herpesvirus 6B Induces Hypomethylation on Chromosome 17p13.3, Correlating with Increased Gene Expression and Virus Integration.

Human herpesvirus 6B (HHV-6B) is a neurotropic betaherpesvirus that achieves latency by integrating its genome into host cell chromosomes. Several viruses can induce epigenetic modifications in their host cells, but no study has investigated the epigenetic modifications induced by HHV-6B. This study analyzed methylation with an Illumina 450K array, comparing HHV-6B-infected and uninfected Molt-3 T cells 3 days postinfection.

Investigation of reference gene expression during human herpesvirus 6B infection indicates peptidylprolyl isomerase A as a stable reference gene and TATA box binding protein as a gene up-regulated by this virus.

When using relative gene expression for quantification of RNA it is crucial that the reference genes used for normalization do not change with the experimental condition. We aimed at investigating the expressional stability of commonly used reference genes during Human herpesvirus 6B (HHV-6B) infection. Expression of eight commonly used reference genes were investigated with quantitative PCR in a T-cell line infected with HHV-6B.

HLA-A(∗)02, gender and tobacco smoking, but not multiple sclerosis, affects the IgG antibody response against human herpesvirus 6.

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system. Both genetic and environmental factors contribute to disease susceptibility and two viruses associated with MS are human herpesvirus (HHV)-6A and HHV-6B, together referred to as HHV-6. This study characterized the plasma IgG antibody response against HHV-6 in MS patients (n=446) and healthy controls (n=487), and the relationship between MS susceptibility factors and the anti-HHV-6 response was investigated.

Anti-interferon beta antibody titers strongly correlate between two bioassays and in vivo biomarker expression, and indicates that a titer of 150 TRU/mL is a biologically functional cut-point.

Interferon beta (IFNβ) is used as a first-line treatment in relapsing-remitting multiple sclerosis (MS). The occurrence of neutralizing antidrug antibodies (NAbs) against IFNβ may reduce treatment response. Therefore, clinical monitoring of NAbs is currently executed using bioassays, but several bioassays are available and it is unclear how well their readouts correlate.

Human herpesvirus 6A partially suppresses functional properties of DC without viral replication.

Human herpesvirus 6A (HHV-6A) is a common virus with a worldwide distribution that has been associated with multiple sclerosis. Whether HHV-6A can replicate in dendritic cells (DC) and how the infection might modulate the functional properties of the cell are currently not well known and need further investigations. Here, we show that a non-productive infection of HHV-6A in DC leads to the up-regulation of HLA-ABC, via autocrine IFN-α signaling, as well as the up-regulation of HLA-DR and CD86.

First therapeutic use of Artesunate in treatment of human herpesvirus 6B myocarditis in a child.

Background: Human herpesvirus 6 (HHV-6) is an important cause of fulminant or acute viral myocarditis. However, insufficiency of standard antiviral treatment against HHV-6 is an emerging problem.

Objectives: To describe the case of child with HHV-6 myocarditis who was treated by unloading with a left ventricular assist device and Artesunate.

Development and validation of a Q-PCR based TCID50 method for human herpesvirus 6.

Background: For titer assessment of human herpesvirus 6 (HHV-6), IFA targeting viral proteins or a TCID(50) method with ocular inspection for CPE can be used. These methods rely on the subjective decision of the assessor, obstructing the ability to obtain unanimous results.

Findings: We have developed and validated an alternative TCID(50) read-out approach where infection in the titration culture plate is assessed by viral DNA load change by quantitative PCR.

Prevalence of anti-drug antibodies against interferon beta has decreased since routine analysis of neutralizing antibodies became clinical practice.

Background: Neutralizing antibodies (NAbs) against interferon beta (IFNβ) lead to loss of treatment efficacy in multiple sclerosis patients. The seroprevalence of NAbs in multiple sclerosis patients treated with IFNβ during 2003-2004 was 32% in a cross-sectional analysis of routine data.

Objectives: The aim of this study was to investigate whether the seroprevalence of NAbs, the levels of NAb titres and the IFNβ preparations used for treatment of multiple sclerosis patients had changed in 2009-2010.