Titanium dioxide (TiO₂) nanoparticles (NPs) are produced abundantly and are frequently used as a white pigment in the manufacture of paints, foods, paper, and toothpaste. Despite the wide ranges of uses, there is a lack of information on the impact of NPs on animal and human health. In the present study, rats were exposed to different doses of TiO₂ nanoparticles and sacrificed, respectively, 4 days, 1 month, and 2 months after treatment. Dosage of TiO₂ in tissues was performed by ICP-AES and revealed an important accumulation of TiO₂ in the liver. The nanoparticles induced morphological and physiological alterations in liver and kidney. In the liver, these alterations mainly affect the hepatocytes located around the centrilobular veins. These cells were the site of an oxidative stress evidenced by immunocytochemical detection of 4-hydroxynonenal (4-HNE). Kupffer cells are also the site of an important oxidative stress following the massive internalization of TiO₂ nanoparticles. Enzymatic markers of liver and kidney functions (such as AST and uric acid) are also disrupted only in animals exposed to highest doses. The metabonomic approach allowed us to detect modifications in urine samples already detectable after 4 days in animals treated at the lowest dose. This metabonomic pattern testifies an oxidative stress as well as renal and hepatic alterations.

Excessive pollen harvesting by bees can compromise the reproductive success of plants. Plants have therefore evolved different morphological structures and floral cues to narrow the spectrum of pollen feeding visitors. Among “filtering” mechanisms, the chemical and mechanical protection of pollen might shape bee-flower interactions and restrict pollen exploitation to a specific suite of visitors such as observed in Asteraceae. Asteraceae pollen is indeed only occasionally exploited by generalist bee species but plentifully foraged by specialist ones (i.e., Asteraceae paradox). During our bioassays, we observed that micro-colonies of generalist bumblebee (Bombus terrestris L.) feeding on Taraxacum pollen (Asteraceae) reduced their pollen collection and offspring production. Bees also experienced physiological effects of possible defenses in the form of digestive damage. Overall, our results suggest the existence of an effective chemical defense in Asteraceae pollen, while the hypothesis of a mechanical defense appeared more unlikely. Pre- and post-ingestive effects of such chemical defenses (i.e., nutrient deficit or presence of toxic compounds), as well as their role in the shaping of bee-flower interactions, are discussed. Our results strongly suggest that pollen chemical traits may act as drivers of plant selection by bees and partly explain why Asteraceae pollen is rare in generalist bee diets.

Blood-brain barrier (BBB) crossing and brain penetration are really challenging for the delivery of therapeutic agents and imaging probes. The development of new crossing strategies is needed, and a wide range of approaches (invasive or not) have been proposed so far. The receptor-mediated transcytosis is an attractive mechanism, allowing the non-invasive penetration of the BBB. Among available targets, the low-density lipoprotein (LDL) receptor (LDLR) shows favorable characteristics mainly because of the lysosome-bypassed pathway of LDL delivery to the brain, allowing an intact discharge of the carried ligand to the brain targets. The phage display technology was employed to identify a dodecapeptide targeted to the extracellular domain of LDLR (ED-LDLR). This peptide was able to bind the ED-LDLR in the presence of natural ligands and dissociated at acidic pH and in the absence of calcium, in a similar manner as the LDL. In vitro, our peptide was endocytosed by endothelial cells through the caveolae-dependent pathway, proper to the LDLR route in BBB, suggesting the prevention of its lysosomal degradation. The in vivo studies performed by magnetic resonance imaging and fluorescent lifetime imaging suggested the brain penetration of this ED-LDLR-targeted peptide.

Background: The skeleton is the first and most common distant metastatic site for breast cancer. Such metastases complicate cancer management, inducing considerable morbidities and decreasing patient survival. Osteomimetism is part of the complex process of osteotropism of breast cancer cells. Recent data indicate that Farnesoid X Receptor (FXR) is involved in the transformation and progression of breast cancer. Methods: The expression of FXR, Runt-related transcription factor 2 (RUNX2) and bone proteins were evaluated on two tumor cell lines (MCF-7 and MDA-MB-231) by immunohistochemistry, immunofluorescence and western blotting and quantified. Results: In a series of 81 breast cancer patients who developed distant metastases, we found a strong correlation between FXR expression in primary breast tumors and the development of bone metastases, especially in patients with histological grade 3 tumors. In in vitro studies, FXR activation by Chenodeoxycholic acid (CDCA) increased the expression of numerous bone proteins. FXR inhibition by lithocholic acid and z-guggulsterone decreased bone protein expression. Short Hairpin RNA (ShRNA) against FXR validated the involvement of FXR in the osteomimetism of breast cancer cells. Conclusion: Our experimental results point to a relationship between the expression of FXR in breast cancer cells and the propensity of these tumor cells to develop bone metastases. FXR induces the expression of RUNX2 which itself causes the synthesis of bone proteins by tumor cells.

In this work, aqueous solutions of magnetite nanoparticles (NPs) are studied. Magnetite NPs are very useful in biomedicine for magnetic resonance imaging (MRI), for drug delivery therapy, and also for hyperthermia. In order to predict the NP efficiency in these applications, it is crucial to accurately characterize their size distribution and their magnetization. Magnetometry, through the dependence of NP magnetization on the magnetic induction (MB curve), can provide interesting information on these physical properties. In this work, the extraction of the NP size distribution and magnetization from experimental MB curves of aqueous solutions of magnetite NPs is discussed. The results are compared to TEM and XRD characterizations. It is shown that an expression taking into account the size distribution better fits the results than the commonly used simple Langevin function. The size distributions obtained by magnetometry seem comparable to those obtained by TEM measurements. However, a closer look at the results shows some nonnegligible discrepancies: the size distributions obtained by magnetometry vary with the temperature and are closer to the TEM ones at room temperature. Our study suggests that it could be explained by the nonnegligible anisotropy energy of the NPs at low temperature and the lack of NP Brownian rotation below the freezing point of water. This demonstrates that care must be taken when interpreting the results obtained by magnetometry of magnetite NPs: only the size and size distribution obtained at room temperature should be used.