ERα36–GPER1 Collaboration Inhibits TLR4/NFκB-Induced Pro-Inflammatory Activity in Breast Cancer Cells

Inflammation is important for the initiation and progression of breast cancer. We have previously reported that in monocytes, estrogen regulates TLR4/NFκB-mediated inflammation via the interaction of the Erα isoform ERα36 with GPER1. We therefore investigated whether a similar mechanism is present in breast cancer epithelial cells, and the effect of ERα36 expression on the classic 66 kD ERα isoform (ERα66) functions. We report that estrogen inhibits LPS-induced NFκB activity and the expression of downstream molecules TNFα and IL-6. In the absence of ERα66, ERα36 and GPER1 are both indispensable for this effect. In the presence of ERα66, ERα36 or GPER1 knock-down partially inhibits NFκB-mediated inflammation. In both cases, ERα36 overexpression enhances the inhibitory effect of estrogen on inflammation. We also verify that ERα36 and GPER1 physically interact, especially after LPS treatment, and that GPER1 interacts directly with NFκB. When both ERα66 and ERα36 are expressed, the latter acts as an inhibitor of ERα66 via its binding to estrogen response elements. We also report that the activation of ERα36 leads to the inhibition of breast cancer cell proliferation. Our data support that ERα36 is an inhibitory estrogen receptor that, in collaboration with GPER1, inhibits NFκB-mediated inflammation and ERα66 actions in breast cancer cells.     

Optimisation of octadecyl (C18) sorbent amount in QuEChERS analytical method for the accurate organophosphorus pesticide residues determination in low-fatty baby foods with response surface methodology

Three low-fatty baby food matrices were fortified with 0.01–0.2 mg/kg of phorate, diazinon, chlorpyrifos and methidathion. A “quick, easy, cheap, effective, rugged and safe” – like method (QuEChERS) was used. Quantities of octadecyl (C₁₈) sorbent differed with fortification level and matrix fat, based on central composite experimental design. Quantification was performed by Nitrogen–Phosphorus Detector gas chromatography, using matrix-matched standards. The highest (p < 0.05) recoveries were observed for methidathion, the lowest fortification levels for a specific C₁₈ amount and the lowest C₁₈ amounts. In meals containing vegetables (1.9% fat) and lamb (3.0% fat), 180–210 mg C₁₈ gave recoveries from 67.0% to 105.0% and absence of co-extracts. Yogurt dessert (4.5% fat) required 200–230 mg C₁₈ for similar results. Recoveries could also be predicted with <20% error by a polynomial model. The results suggest that modified QuEChERS could be effectively used in the low-fatty baby meals residue analysis.     

The Sexually Dimorphic Adrenal Cortex: Implications for Adrenal Disease

Many adrenocortical diseases are more prevalent in women than in men, but the reasons underlying this sex bias are still unknown. Recent studies involving gonadectomy and sex hormone replacement experiments in mice have shed some light onto the molecular basis of sexual dimorphism in the adrenal cortex. Indeed, it has been shown that gonadal hormones influence many aspects of adrenal physiology, ranging from stem cell-dependent tissue turnover to steroidogenesis and X-zone dynamics. This article reviews current knowledge on adrenal cortex sexual dimorphism and the potential mechanisms underlying sex hormone influence of adrenal homeostasis. Both topics are expected to contribute to personalized and novel therapeutic approaches in the future.