A Comparative Study of the In Vitro Intestinal Permeability of Pinnatoxins and Portimine.

The pinnatoxins (PnTXs) and portimines, produced by , have been detected in several countries, raising concerns for human health. Although no human poisoning from these toxins has been reported so far, they have been shown to distribute throughout the rodent body after oral administration. Therefore, we investigated the impact of PnTX analogs (PnTX-A, -E, -F, -G, and -H) and portimine (8, 16, and 32 ng/mL) on intestinal barrier integrity and their oral bioavailability using human Caco-2 cell monolayers treated for 2, 6, and 24 h.

Human next-generation risk assessment of trichothecene toxicity.

Trichothecenes are naturally occurring chemicals, produced by fungi, that can be found in contaminated crops. Trichothecenes have the potential to indirectly damage DNA and exacerbate genotoxic effects of genotoxicants. However, genotoxicity data for most trichothecenes are limited and data gaps remain.

Transcriptional landscape of human keratinocyte models exposed to 60-GHz millimeter-waves.

The use of millimeter waves (MMW) will exponentially grow in the coming years due to their future utilization in 5G/6G networks. The question of possible biological effects at these frequencies has been raised. In this present study, we aimed to investigate gene expression changes under exposure to MMW using the Bulk RNA Barcoding and sequencing (BRB-seq) technology.

Combined in silico and in vitro approaches to identify P-glycoprotein-inhibiting pesticides.

The P-glycoprotein (P-gp) efflux pump plays a major role in xenobiotic detoxification. The inhibition of its activity by environmental contaminants remains however rather little characterised. The present study was designed to develop a combination of different approaches to identify P-gp inhibitors among a large number of pesticides using in silico and in vitro models.

Prioritization of mycotoxins based on mutagenicity and carcinogenicity evaluation using combined in silico QSAR methods.

Mycotoxins and their metabolites are a family of compounds that contains a great diversity of both structure and biological properties. Information on their toxicity is spread within several databases and in scientific literature. Due to the number of molecules and their structure diversity, the cost and time required for hazard evaluation of each compound is unrealistic.

Hypoxia and ERα Transcriptional Crosstalk Is Associated with Endocrine Resistance in Breast Cancer.

Estrogen receptor-alpha (ERα) is the driving transcription factor in 70% of breast cancers and its activity is associated with hormone dependent tumor cell proliferation and survival. Given the recurrence of hormone resistant relapses, understanding the etiological factors fueling resistance is of major clinical interest. Hypoxia, a frequent feature of the solid tumor microenvironment, has been described to promote endocrine resistance by triggering ERα down-regulation in both in vitro and in vivo models.

Key parameter optimization using multivariable linear model for the evaluation of the in vitro estrogenic activity assay in T47D cell lines (CXCL-test).

In comparison with analytical tools, bioassays provide higher sensitivity and more complex evaluation of environmental samples and are indispensable tools for monitoring increasing in anthropogenic pollution. Nevertheless, the disadvantage in cellular assays stems from the material variability used within the assays, and an interlaboratory adaptation does not usually lead to satisfactory test sensitivities. The aim of this study was to evaluate the influence of material variability on CXCL12 secretion by T47D cells, the outcome of the CXCL-test (estrogenic activity assay).

Comparative in silico prediction of P-glycoprotein-mediated transport for 2010-2020 US FDA-approved drugs using six Web-tools.

P-glycoprotein (P-gp) is an efflux pump implicated in pharmacokinetics and drug-drug interactions. The identification of its substrates is consequently an important issue, notably for drugs under development. For such a purpose, various in silico methods have been developed, but their relevance remains to be fully established.

Effects of radiofrequency field exposure on proteotoxic-induced and heat-induced HSF1 response in live cells using the bioluminescence resonance energy transfer technique.

As of today, only acute effects of RF fields have been confirmed to represent a potential health hazard and they are attributed to non-specific heating (≥ 1 °C) under high-level exposure. Yet, the possibility that environmental RF impact living matter in the absence of temperature elevation needs further investigation. Since HSF1 is both a thermosensor and the master regulator of heat-shock stress response in eukaryotes, it remains to assess HSF1 activation in live cells under exposure to low-level RF signals.

Evaluation of the Effect of Chronic 94 GHz Exposure on Gene Expression in the Skin of Hairless Rats .

Millimeter waves (MMW) are broadband frequencies that have recently been used in several applications in wireless communications, medical devices and nonlethal weapons [i.e., the nonlethal weapon, Active Denial Systems, (ADS) operating at 94-95 GHz, CW].

Nuclear accumulation of MKL1 in luminal breast cancer cells impairs genomic activity of ERα and is associated with endocrine resistance.

Estrogen receptor (ERα) is central in driving the development of hormone-dependent breast cancers. A major challenge in treating these cancers is to understand and overcome endocrine resistance. The Megakaryoblastic Leukemia 1 (MKL1, MRTFA) protein is a master regulator of actin dynamic and cellular motile functions, whose nuclear translocation favors epithelial-mesenchymal transition.

Critical parameters in surface plasmon resonance biosensor development: The interaction between estrogen receptor and estrogen response element as model.

Estrogenic compounds are contaminants that may be active at low concentrations and are a major concern for environmental quality. They interact with organisms via Estrogen Receptors (ER). Some detection methods which have been developed use the ability of ER to interact with short consensus DNA sequences known as Estrogen Response Elements (ERE).

Untargeted metabolomics unveil alterations of biomembranes permeability in human HaCaT keratinocytes upon 60 GHz millimeter-wave exposure.

A joint metabolomic and lipidomic workflow is used to account for a potential effect of millimeter waves (MMW) around 60 GHz on biological tissues. For this purpose, HaCaT human keratinocytes were exposed at 60.4 GHz with an incident power density of 20 mW/cm², this value corresponding to the upper local exposure limit for general public in the context of a wide scale deployment of MMW technologies and devices.

Untargeted Metabolomics Reveal Lipid Alterations upon 2-Deoxyglucose Treatment in Human HaCaT Keratinocytes.

The glucose analogue 2-deoxyglucose (2-DG) impedes cancer progression in animal models and is currently being assessed as an anticancer therapy, yet the mode of action of this drug of high clinical significance has not been fully delineated. In an attempt to better characterize its pharmacodynamics, an integrative UPLC-Q-Exactive-based joint metabolomic and lipidomic approach was undertaken to evaluate the metabolic perturbations induced by this drug in human HaCaT keratinocyte cells. R-XCMS data processing and subsequent multivariate pattern recognition, metabolites identification, and pathway analyses identified eight metabolites that were most significantly changed upon a 3 h 2-DG exposure.

Emerging Estrogenic Pollutants in the Aquatic Environment and Breast Cancer.

The number and amount of man-made chemicals present in the aquatic environment has increased considerably over the past 50 years. Among these contaminants, endocrine-disrupting chemicals (EDCs) represent a significant proportion. This family of compounds interferes with normal hormonal processes through multiple molecular pathways.

Rapid assessment of estrogenic compounds by CXCL-test illustrated by the screening of the UV-filter derivative benzophenones.

CXCL-test is a method that uses the estrogen-dependent secretion of the natural endogenous chemokine CXCL12 to evaluate the estrogenic activity of molecules. CXCL12 chemokine is involved in the estrogen dependent proliferation of breast cancer cells. Its measure is an indicator of cell proliferation and is used as an alternative test to classical proliferation test.

Estrogen receptor preparation effects on the receptor-DNA interaction by surface plasmon resonance.

Up to now, several studies have investigated estrogen receptor (ER)-estrogen response element (ERE) interaction using biosensors such as surface plasmon resonance. These strategies have aimed to understand the molecular mechanism of such interaction as well as the effect of the ligand on this interaction. These approaches start to be used to determine the mechanisms of protein/DNA interaction, in particular in the context of drug discovery or environmental applications.

Additive Effects of Millimeter Waves and 2-Deoxyglucose Co-Exposure on the Human Keratinocyte Transcriptome.

Millimeter Waves (MMW) will be used in the next-generation of high-speed wireless technologies, especially in future Ultra-Broadband small cells in 5G cellular networks. Therefore, their biocompatibilities must be evaluated prior to their massive deployment. Using a microarray-based approach, we analyzed modifications to the whole genome of a human keratinocyte model that was exposed at 60.

Transcriptome analysis reveals the contribution of thermal and the specific effects in cellular response to millimeter wave exposure.

Radiofrequency radiations constitute a new form of environmental pollution. Among them, millimeter waves (MMW) will be widely used in the near future for high speed communication systems. This study aimed therefore to evaluate the biocompatibility of MMW at 60 GHz.

Impact of 60-GHz millimeter waves and corresponding heat effect on endoplasmic reticulum stress sensor gene expression.

Emerging high data rate wireless communication systems, currently under development, will operate at millimeter waves (MMW) and specifically in the 60 GHz band for broadband short-range communications. The aim of this study was to investigate potential effects of MMW radiation on the cellular endoplasmic reticulum (ER) stress. Human skin cell lines were exposed at 60.

Differentiation of PC12 cells expressing estrogen receptor alpha: a new bioassay for endocrine-disrupting chemicals evaluation.

Xeno-estrogens, a class of endocrine disrupting chemicals (EDCs), can disturb estrogen receptor-dependent pathways involved in differentiation, proliferation or protection. Multiple methods have been developed to characterize the disturbances induced by EDCs in different cells or organs. In this study we have developed a new tool for the assessment of estrogenic compounds on differentiation.

Activation of the MKL1/actin signaling pathway induces hormonal escape in estrogen-responsive breast cancer cell lines.

Estrogen receptor alpha (ERα) is generally considered to be a good prognostic marker because almost 70% of ERα-positive tumors respond to anti-hormone therapies. Unfortunately, during cancer progression, mammary tumors can escape from estrogen control, resulting in resistance to treatment. In this study, we demonstrate that activation of the actin/megakaryoblastic leukemia 1 (MKL1) signaling pathway promotes the hormonal escape of estrogen-sensitive breast cancer cell lines.

Impact of biochemical design on estrogen receptor/estrogen response element interaction by surface plasmon resonance technology.

The estrogen receptor (ER) is a transcription factor that binds under 17-β-estradiol (E2) stimulation as homodimer to a short DNA consensus sequence named estrogen response element (ERE). The ER/ERE interaction has been assessed by several research groups through different methodologies notably by surface plasmon resonance (SPR) techniques. The biochemical parameters and conditions (solvent, ER concentration, salt, time and temperature) used to prepare samples before analysis were very different from one study to another.

Unliganded estrogen receptor alpha promotes PC12 survival during serum starvation.

Many studies have reported proliferative, differentiating or protective effects of estradiol, notably through estrogen receptor alpha (ERα). On the contrary, the ligand-independent action of ERα is currently poorly documented notably in cell protection. The stable transfection of wild type, substituted or truncated form of ERα in PC12 cells (ERα negative cell line) lead the specific study of its ligand-independent action.